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Coronavirus Infections (808) Severe Acute Respiratory Syndrome (560) Infection (466) Pneumonia (365) Communicable Diseases (197) Respiratory Distress Syndrome, Adult (178) Acute Lung Injury (143) Respiratory Distress Syndrome, Newborn (143) (130) Syndrome (105) Virus Diseases (87) Pneumonia, Viral (82) Depression (65) Critical Illness (62) Anxiety Disorders (38) Respiratory Tract Infections (36) Cardiovascular Diseases (35) Emergencies (35) Stress, Psychological (31) Lung Injury (30) Neoplasms (30) Inflammation (29) Stress Disorders, Post-Traumatic (29) Wounds and Injuries (29) Hypoxia (28) Thrombosis (28) Diabetes Mellitus (26) Disease (25) Respiratory Tract Diseases (25) Stress Disorders, Traumatic (25) Depressive Disorder (24) Acute Kidney Injury (22) Disease Progression (22) Lung Diseases (22) Mental Disorders (21) Burnout, Psychological (19) Olfaction Disorders (19) Respiration Disorders (19) Thromboembolism (19) Hypertension (18) Embolism (16) Arthritis (15) Blood Coagulation Disorders (15) Hemostatic Disorders (15) Pulmonary Embolism (15) Pulmonary Fibrosis (15) Lung Diseases, Interstitial (14) Stroke (14) Respiratory Aspiration (13) Diabetes Mellitus, Type 2 (12) Fibrosis (12) Arthritis, Rheumatoid (11) Influenza, Human (11) Rheumatic Diseases (11) Venous Thrombosis (11) Dyspnea (10) Burnout, Professional (9) Chronic Pain (9) Cognitive Dysfunction (9) Collagen Diseases (9) Diabetes Mellitus, Type 1 (9) Myocardial Infarction (9) Pneumonia, Ventilator-Associated (9) Pregnancy Complications (9) Problem Behavior (9) Venous Thromboembolism (9) Vitamin D Deficiency (9) Heart Failure (8) Infarction (8) Liver Diseases (8) Myocarditis (8) Parasomnias (8) RNA Virus Infections (8) Sclerosis (8) Sepsis (8) Convalescence (7) Depression, Postpartum (7) Dyssomnias (7) Heart Diseases (7) Hematologic Neoplasms (7) Infertility (7) Inflammatory Bowel Diseases (7) Lung Diseases, Obstructive (7) Lymphopenia (7) Multiple Sclerosis (7) Pulmonary Valve Insufficiency (7) Shock (7) Frailty (6) Immunologic Deficiency Syndromes (6) Lung Neoplasms (6) Lupus Erythematosus, Systemic (6) Lymphoma (6) Neurologic Manifestations (6) Obesity (6) Pulmonary Disease, Chronic Obstructive (6) Autoimmune Diseases (5) Brain Diseases (5) Brain Injuries (5) Breast Neoplasms (5) Chronic Disease (5) Coronaviridae Infections (5) Cross Infection (5) Delirium (5) Disease Susceptibility (5) Disseminated Intravascular Coagulation (5) Fatigue (5) Feeding and Eating Disorders (5) HIV Infections (5) Immune System Diseases (5) Kidney Diseases (5) Kidney Failure, Chronic (5) Multiple Organ Failure (5) Occupational Stress (5) Parkinson Disease (5) Thrombophilia (5) Toxemia (5) Acquired Immunodeficiency Syndrome (4) Acute Coronary Syndrome (4) Anemia, Sickle Cell (4) Appendicitis (4) Arrhythmias, Cardiac (4) Arthritis, Psoriatic (4) Asymptomatic Diseases (4) Autism Spectrum Disorder (4) Carcinoma (4) Coinfection (4) Colonic Neoplasms (4) Coronary Artery Disease (4) Coronary Disease (4) Death (4) Embolism and Thrombosis (4) Headache (4) Heart Arrest (4) Leukemia (4) Musculoskeletal Pain (4) Mycobacterium Infections (4) Nervous System Diseases (4) Postoperative Complications (4) Signs and Symptoms, Respiratory (4) Substance-Related Disorders (4) Tuberculosis (4) Ventricular Dysfunction (4) Ventricular Dysfunction, Left (4) Adenoviridae Infections (3) Alcoholism (3) Asthma (3) Attention Deficit Disorder with Hyperactivity (3) Autistic Disorder (3) Bronchiectasis (3) Cardiomyopathies (3) Chilblains (3) Colorectal Neoplasms (3) Cystic Fibrosis (3) Deglutition Disorders (3) Digestive System Diseases (3) Dysgeusia (3) Ganglion Cysts (3) Gastrointestinal Diseases (3) Giant Cell Arteritis (3) Head and Neck Neoplasms (3) Hemorrhage (3) Hypertension, Pulmonary (3) Ischemia (3) Leukemia, Lymphocytic, Chronic, B-Cell (3) Measles (3) Melanoma (3) Metabolic Diseases (3) Migraine Disorders (3) (3) Myeloproliferative Disorders (3) Myocardial Ischemia (3) Obesity, Morbid (3) Pancreatic Neoplasms (3) Polymyalgia Rheumatica (3) Pregnancy Complications, Infectious (3) Psoriasis (3) Pulmonary Edema (3) Rare Diseases (3) Renal Insufficiency, Chronic (3) Rheumatic Fever (3) Sjogren's Syndrome (3) Sleep Initiation and Maintenance Disorders (3) Sleep Wake Disorders (3) Spinal Cord Injuries (3) Spondylarthritis (3) Systemic Inflammatory Response Syndrome (3) Taste Disorders (3) Acute Disease (2) Ageusia (2) Alcohol Drinking (2) Alopecia (2) Amyotrophic Lateral Sclerosis (2) Anorexia (2) Anorexia Nervosa (2) Arteritis (2) Asymptomatic Infections (2) Atrial Fibrillation (2) Bacteremia (2) Behcet Syndrome (2) Bipolar Disorder (2) Brain Injuries, Traumatic (2) Carcinoma, Renal Cell (2) Child Development Disorders, Pervasive (2) Cholangiocarcinoma (2) Cholangitis (2) Clinical Deterioration (2) Compassion Fatigue (2) Congenital Abnormalities (2) Conjunctivitis (2) (2) Dementia (2) Depressive Disorder, Major (2) Diarrhea (2) Drug-Related Side Effects and Adverse Reactions (2) Encephalitis (2) Endocrine System Diseases (2) Eye Diseases (2) Fever (2) Fibromyalgia (2) Fractures, Bone (2) Fractures, Stress (2) Genetic Predisposition to Disease (2) Glucose Metabolism Disorders (2) Heart Defects, Congenital (2) Hematologic Diseases (2) Hepatitis C (2) Hypersensitivity (2) Hypothermia (2) Idiopathic Pulmonary Fibrosis (2) Infertility, Male (2) Intestinal Diseases (2) Jaundice (2) Leukemia, Lymphoid (2) Liver Cirrhosis (2) Lymphoma, Mantle-Cell (2) Macular Edema (2) Motor Neuron Disease (2) Mouth Diseases (2) Multiple Myeloma (2) Myelodysplastic Syndromes (2) Myositis (2) Neoplasm Metastasis (2) Neoplasms, Plasma Cell (2) Nerve Degeneration (2) Neuroendocrine Tumors (2) Nidovirales Infections (2) Noncommunicable Diseases (2) Obstetric Labor, Premature (2) Oral Manifestations (2) (2) Overweight (2) Pediatric Obesity (2) Pneumonia, Pneumocystis (2) Precursor Cell Lymphoblastic Leukemia-Lymphoma (2) Premature Birth (2) Psychological Trauma (2) Psychotic Disorders (2) Rectal Neoplasms (2) Renal Insufficiency (2) ST Elevation Myocardial Infarction (2) Sarcopenia (2) (2) Scleroderma, Systemic (2) Seizures (2) Shock, Septic (2) Sleep Apnea Syndromes (2) Sleep Apnea, Obstructive (2) Stillbirth (2) Suicide (2) Thyroid Diseases (2) Uterine Cervical Neoplasms (2) Vision Disorders (2) Vision, Low (2) Abruptio Placentae (1) Acalculous Cholecystitis (1) (1) Adenocarcinoma (1) Adjustment Disorders (1) Adrenal Insufficiency (1) Alcohol-Related Disorders (1) Alcoholic Intoxication (1) Alpha 1-Antitrypsin Deficiency (1) Altitude Sickness (1) Alzheimer Disease (1) Amblyopia (1) Anemia, Aplastic (1) Aneurysm (1) Angina Pectoris (1) Ankle Fractures (1) Aortic Valve Stenosis (1) Apnea (1) Arthritis, Juvenile (1) Atherosclerosis (1) Atrioventricular Block (1) Atrophy (1) Autonomic Nervous System Diseases (1) Bacterial Infections (1) Barotrauma (1) Behavior, Addictive (1) Binge-Eating Disorder (1) Blister (1) Body Weight (1) Body Weight Changes (1) Bradycardia (1) Bronchopulmonary Dysplasia (1) Brucellosis (1) Bulimia (1) Bulimia Nervosa (1) Carcinoma in Situ (1) Carcinoma, Ductal (1) Carcinoma, Ductal, Breast (1) Carcinoma, Hepatocellular (1) Carcinoma, Intraductal, Noninfiltrating (1) Cardiovascular Abnormalities (1) Cataract (1) Cellulitis (1) Central Nervous System Neoplasms (1) Cerebral Hemorrhage (1) Cerebral Palsy (1) Cholangitis, Sclerosing (1) Cholecystitis (1) Cholecystitis, Acute (1) Chronic Traumatic Encephalopathy (1) Ciliary Motility Disorders (1) Cognition Disorders (1) Colitis (1) Colitis, Ulcerative (1) Colonic Diseases (1) (1) Common Cold (1) Communicable Diseases, Emerging (1) Communication Disorders (1) Consciousness Disorders (1) Constriction, Pathologic (1) Conversion Disorder (1) (1) Coronavirus Infect (1) (1) Crohn Disease (1) Deafness (1) Death, Sudden, Cardiac (1) Dental Caries (1) Depressive Disorder, Treatment-Resistant (1) Dermatitis (1) Developmental Disabilities (1) DiGeorge Syndrome (1) Digestive System Neoplasms (1) Diphtheria (1) Down Syndrome (1) Dyskinesias (1) Dyspareunia (1) Dysphonia (1) (1) Emergence Delirium (1) Emphysema (1) Endocarditis (1) Endometrial Neoplasms (1) Endometriosis (1) Endophthalmitis (1) Endotoxemia (1) Epilepsy (1) Esophageal Neoplasms (1) Esophageal and Gastric Varices (1) Eye Infections (1) Facial Pain (1) Facies (1) Familial Mediterranean Fever (1) Fatigue Syndrome, Chronic (1) Femoral Fractures (1) Femoral Neck Fractures (1) Fetal Growth Retardation (1) Fetal Membranes, Premature Rupture (1) Fractures, Closed (1) Gambling (1) Gastroenteritis (1) Gastroesophageal Reflux (1) Gestational Weight Gain (1) Glioblastoma (1) Headache Disorders, Secondary (1) Healthcare-Associated Pneumonia (1) Hearing Loss (1) Hearing Loss, Conductive (1) Heart Block (1) Heart Failure, Systolic (1) Hemoglobinopathies (1) Hemophilia A (1) Hepatitis (1) Hereditary Autoinflammatory Diseases (1) Herpes Labialis (1) Herpes Zoster (1) Hoarseness (1) Humeral Fractures (1) Hyperaldosteronism (1) Hyperglycemia (1) Hyperkinesis (1) Hyperphosphatemia (1) Hyperplasia (1) Hypertension, Pregnancy-Induced (1) Hypertrophy (1) Hypokalemia (1) Hyponatremia (1) Hypotension (1) Hypoventilation (1) (1) Infant, Newborn, Diseases (1) (1) Infec (1) Infecti (1) Infertility, Female (1) Intellectual Disability (1) Intestinal Atresia (1) Intracranial Aneurysm (1) Intracranial Hypertension (1) Intracranial Thrombosis (1) Jaundice, Obstructive (1) Joint Diseases (1) Keratoconjunctivitis (1) Kidney Neoplasms (1) Laryngeal Neoplasms (1) Latent Tuberculosis (1) Leukemia, Myeloid, Acute (1) Liver Cirrhosis, Biliary (1) Liver Failure (1) Liver Neoplasms (1) Lymphedema (1) Lymphocytosis (1) Lymphoma, B-Cell (1) Lymphoma, Non-Hodgkin (1) Macrophage Activation Syndrome (1) Macular Degeneration (1) Malnutrition (1) Maternal Death (1) Maxillofacial Injuries (1) Memory Disorders (1) Meningitis (1) Meningitis, Meningococcal (1) Menorrhagia (1) Menstruation Disturbances (1) Metabolic Syndrome (1) Metabolism, Inborn Errors (1) Microvascular Rarefaction (1) Mitochondrial Diseases (1) Mobility Limitation (1) Monoclonal Gammopathy of Undetermined Significance (1) Mood Disorders (1) Mouth, Edentulous (1) Movement Disorders (1) Mucocutaneous Lymph Node Syndrome (1) Multiple Chronic Conditions (1) Muscular Atrophy (1) Muscular Dystrophies (1) Myalgia (1) Mycoses (1) Myocardial Reperfusion Injury (1) Myofascial Pain Syndromes (1) Necrosis (1) Needlestick Injuries (1) Neonatal Sepsis (1) Neoplastic Cells, Circulating (1) Nephritis (1) Nervous System Malformations (1) Nervous System Neoplasms (1) Neurocognitive Disorders (1) Neuromuscular Diseases (1) Neuromyelitis Optica (1) Nutrition Disorders (1) Obsessive Behavior (1) Oligospermia (1) Orbital Cellulitis (1) Osteoarthritis (1) Osteoarthritis, Hip (1) Osteoarthritis, Knee (1) Osteochondritis (1) Otitis Media with Effusion (1) Ovarian Neoplasms (1) Pain, Intractable (1) Pancreatitis (1) Paramyxoviridae Infections (1) Paraproteinemias (1) Paresis (1) Parkin (1) Perinatal Death (1) Periodontal Diseases (1) Periodontitis (1) Pharyngeal Diseases (1) Pneumon (1) Pneumonia, Bacterial (1) Pre-Eclampsia (1) Prediabetic State (1) Pregnancy in Diabetics (1) Primary Dysautonomias (1) Prostatic Hyperplasia (1) Protein Deficiency (1) Pseudomonas Infections (1) Psychophysiologic Disorders (1) Puerperal Infection (1) Pulmonary Alveolar Proteinosis (1) Pulmonary Atelectasis (1) Pulmonary Eosinophilia (1) Pulmonary Heart Disease (1) Purpura, Thrombocytopenic, Idiopathic (1) Recurrence (1) Reperfusion Injury (1) Resp (1) Respiratory Distress Sy (1) Respiratory Syncytial Virus Infections (1) Retinal Vein Occlusion (1) Rupture (1) Sarcoidosis (1) Scleroderma, Localized (1) (1) Shock, Cardiogenic (1) Shoulder Fractures (1) Skin Diseases (1) Skin Manifestations (1) Skin Neoplasms (1) Skull Fractures (1) Somatoform Disorders (1) Spondylitis (1) Spondylitis, Ankylosing (1) Sprains and Strains (1) Status Epilepticus (1) Stomach Neoplasms (1) Stress Disorders, Traumatic, Acute (1) Subarachnoid Hemorrhage (1) Suicidal Ideation (1) Superinfection (1) Synovial Cyst (1) Tachycardia (1) Tachycardia, Ventricular (1) Tachypnea (1) Testicular Neoplasms (1) Thalassemia (1) Thoracic Diseases (1) Thrombocytopenia (1) Thrombophlebitis (1) Thrombotic Microangiopathies (1) Tobacco Use Disorder (1) Tonsillitis (1) Torsades de Pointes (1) Tourette Syndrome (1) Trauma, Nervous System (1) Tuberculosis, Pulmonary (1) Urinary Tract Infections (1) Urogenital Neoplasms (1) Urologic Diseases (1) Uterine Neoplasms (1) Vaginal Neoplasms (1) Vascular Diseases (1) Ventricular Dysfunction, Right (1) Virus (1) Vitamin D Deficie (1) Voice Disorders (1) Vulvar Neoplasms (1) Waldenstrom Macroglobulinemia (1) Weight Gain (1) Weight Loss (1) Yellow Fever (1) beta-Thalassemia (1)

D011014: Pneumon

Developed by Shray Alag, The Harker School
Sections: Correlations, Clinical Trials, and HPO

Correlations computed by analyzing all clinical trials.

Navigate: Clinical Trials and HPO


Correlated Drug Terms (576)


Name (Synonyms) Correlation
drug2448 Placebo Wiki 0.17
drug1995 Methylprednisolone Wiki 0.13
drug3375 Tocilizumab Wiki 0.12
Name (Synonyms) Correlation
drug2584 Prednisone Wiki 0.10
drug1936 Mavrilimumab Wiki 0.10
drug3469 UC-MSCs Wiki 0.09
drug1472 Hydroxychloroquine Wiki 0.09
drug3386 Tofacitinib Wiki 0.09
drug2304 Oseltamivir Wiki 0.09
drug4022 standard care Wiki 0.08
drug2286 Opaganib Wiki 0.08
drug333 Azithromycin Wiki 0.08
drug3063 SivoMixx (200 billion) Wiki 0.07
drug133 Abidol hydrochloride Wiki 0.07
drug1829 Low Dose Radiation Therapy Wiki 0.07
drug3930 oxygen therapy Wiki 0.07
drug1111 EXO 2 inhalation Wiki 0.07
drug4078 vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki 0.07
drug1312 Fostamatinib Wiki 0.07
drug4079 vv-ECMO only (no cytokine adsorption) Wiki 0.07
drug2499 Placebo inhalation Wiki 0.07
drug1110 EXO 1 inhalation Wiki 0.07
drug1004 Dexamethasone injection Wiki 0.07
drug1084 EC-18 Wiki 0.07
drug394 Baricitinib Oral Tablet Wiki 0.07
drug1846 Low molecular weight heparin Wiki 0.07
drug3810 hydroxychloroquine Wiki 0.07
drug1869 Lung ultrasound Wiki 0.06
drug2532 Placebos Wiki 0.06
drug776 Clopidogrel Wiki 0.06
drug2616 Prone Positioning Wiki 0.06
drug264 Apremilast Wiki 0.06
drug1982 Mesenchymal stromal cells Wiki 0.06
drug1770 Lenzilumab Wiki 0.06
drug1822 Lopinavir/ritonavir Wiki 0.06
drug3058 Single passive leg movement Wiki 0.05
drug1646 Interferon-β1a Wiki 0.05
drug1376 HB-adMSC Wiki 0.05
drug241 Antibiotic Wiki 0.05
drug2520 Placebo to Match RDV Wiki 0.05
drug2333 PF-06650833 Wiki 0.05
drug282 Aspirin 100mg Wiki 0.05
drug4071 ventilatory support with oxygen therapy Wiki 0.05
drug1722 Ivermectin oral Wiki 0.05
drug3479 Ultra-Low-dose radiotherapy Wiki 0.05
drug796 Colchicine plus symptomatic treatment (paracetamol) Wiki 0.05
drug1290 Fixed-duration Hydrocortisone Wiki 0.05
drug2832 Ritonavir+Oseltamivir Wiki 0.05
drug4047 thalidomide Wiki 0.05
drug294 Assessment of ventilator-associated pneumonia criteria Wiki 0.05
drug1243 FNC dummy tablet+Standard of Care Wiki 0.05
drug4087 Оxygen therapy Wiki 0.05
drug885 Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) Wiki 0.05
drug3811 hydroxychloroquine + azithromycin Wiki 0.05
drug2939 Saline Control Wiki 0.05
drug529 Burnout Wiki 0.05
drug1587 Imatinib Mesylate Wiki 0.05
drug3874 microcirculation recording Wiki 0.05
drug254 Antiviral Agents Wiki 0.05
drug1481 Hydroxychloroquine + placebo Wiki 0.05
drug2801 Respiratory Exercise Training Wiki 0.05
drug2199 Non-enhanced CT scan of the chest Wiki 0.05
drug2764 Recombinant human plasma gelsolin (Rhu-pGSN) Wiki 0.05
drug1626 Inhaled budesonide Wiki 0.05
drug1071 Drug: NA-831 - 0.10 mg/kg Wiki 0.05
drug1742 L-citrulline Wiki 0.05
drug948 DB-001 Wiki 0.05
drug3781 favorable outcome Wiki 0.05
drug1878 MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg Wiki 0.05
drug225 Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki 0.05
drug1896 MSCs Wiki 0.05
drug423 Bevacizumab Wiki 0.05
drug300 AstroStem-V Wiki 0.05
drug2504 Placebo of FX06 Wiki 0.05
drug703 Ceftaroline Wiki 0.05
drug3369 Tinzaparin or unfractionated heparin Wiki 0.05
drug234 Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki 0.05
drug3713 canakinumab Wiki 0.05
drug730 Chest MRI Wiki 0.05
drug1804 Lopinavir Wiki 0.05
drug1531 Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device) Wiki 0.05
drug2038 Molgramostim nebuliser solution Wiki 0.05
drug2083 NK Cells Wiki 0.05
drug1875 MAS825 Wiki 0.05
drug3162 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki 0.05
drug1961 Melphalan Wiki 0.05
drug268 Arbidol Hydrochloride Granules Wiki 0.05
drug245 Antibody testing Wiki 0.05
drug1850 Low-dose Chest CT Wiki 0.05
drug1119 Echo-Doppler Wiki 0.05
drug1617 Information Wiki 0.05
drug1871 LungFit™ Wiki 0.05
drug3050 Simple chest tomography Wiki 0.05
drug2067 N-acetyl cysteine Wiki 0.05
drug596 COVID-19 PCR and Serology Wiki 0.05
drug3863 management strategy of outpatient with mild to moderate SARS-CoV-2 pneumonia Wiki 0.05
drug1894 MSC Treatment Wiki 0.05
drug886 Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules Wiki 0.05
drug1329 GO2 PEEP MOUTHPIECE Wiki 0.05
drug3938 personal protective Measures Wiki 0.05
drug2300 Oral supplement enriched in antioxidants Wiki 0.05
drug3825 immune plasma Wiki 0.05
drug1866 Lung Low Dose Radiation Wiki 0.05
drug3796 high flow nasal cannula device Wiki 0.05
drug3821 iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki 0.05
drug2476 Placebo Group Wiki 0.05
drug490 Bone Marrow Harvest Wiki 0.05
drug1879 MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg Wiki 0.05
drug1429 High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Wiki 0.05
drug1479 Hydroxychloroquine + azithromycin + / - tocilizumab Wiki 0.05
drug2524 Placebo- 1.00 mg/kg Wiki 0.05
drug1508 Hydroxychloroquine and azithromycin treatment arm. Wiki 0.05
drug2164 Nitric Oxide-Continuous and Sessions Wiki 0.05
drug3591 WFI water nebulization Wiki 0.05
drug520 Bromhexine Hydrochloride Tablets Wiki 0.05
drug3944 placebo (hartmann plus albumine) Wiki 0.05
drug369 BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki 0.05
drug1423 High dose radiation 100 cGy Wiki 0.05
drug1543 ID NOW vs. Accula Wiki 0.05
drug227 Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients Wiki 0.05
drug3678 anti-SARS-CoV-2 plasma Wiki 0.05
drug949 DFV890 Wiki 0.05
drug564 COR-101 Wiki 0.05
drug320 Automated oxygen administration - FreeO2 Wiki 0.05
drug842 Continuation of ACEi/ARB Wiki 0.05
drug4024 standard medical treatment Wiki 0.05
drug3263 TXA127 Wiki 0.05
drug2318 Oxygen-ozone therapy, probiotic supplementation and Standard of care Wiki 0.05
drug1711 Ivermectin 5 MG/ML oral solution, Aspirin 250 mg tablets Wiki 0.05
drug3628 Yin Hu Qing Wen Granula(low does) Wiki 0.05
drug649 CT of the chest Wiki 0.05
drug2187 No special intervention Wiki 0.05
drug3855 low-molecular-weight heparin Wiki 0.05
drug743 Chloroquine diphosphate Wiki 0.05
drug676 Canakinumab 150 MG/ML [Ilaris] Wiki 0.05
drug58 80 ppm Nitric Oxide delivered through LungFit Delivery System Wiki 0.05
drug3714 captopril 25mg Wiki 0.05
drug2522 Placebo- 0.10 mg/kg Wiki 0.05
drug195 Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment Wiki 0.05
drug3048 Silymarin Wiki 0.05
drug896 CoronaCideTM COVID-19 IgM/IgG Rapid Test and Premier Biotech COVID-19 IgM/IgG Rapid Test Wiki 0.05
drug3239 T memory cells and NK cells Wiki 0.05
drug192 Almitrine Wiki 0.05
drug3341 Therapy Intervention Wiki 0.05
drug2317 Oxygen supply Wiki 0.05
drug390 Bariatric procedures Wiki 0.05
drug2663 Q-NRG Metobolic Cart Device Wiki 0.05
drug3471 ULTRAPROTECTIVE VENTILATION Wiki 0.05
drug2400 Pemziviptadil (PB1046) Wiki 0.05
drug1332 GX-19 Wiki 0.05
drug2100 Nanomix eLab® COVID-19 Rapid Antigen Panel (non-interventional) Wiki 0.05
drug2063 N terminal pro B type natriuretic peptide (NTproBNP), D-Dimer, and serum Tropinin - I Wiki 0.05
drug4021 spirometry, thoracic CT, CPET, 6 minute walking test, SF-36 questionnaire Wiki 0.05
drug988 Defibrotide Injection Wiki 0.05
drug1978 Mesenchymal stem cell Wiki 0.05
drug3800 hormones Wiki 0.05
drug3208 Supportive tratment Wiki 0.05
drug548 CHEST CT SCAN Wiki 0.05
drug193 Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C Wiki 0.05
drug3181 Sterile Water for Injection Wiki 0.05
drug1723 Ivermectin plus Nitazoxanide Wiki 0.05
drug2482 Placebo Saline Wiki 0.05
drug4077 vv-ECMO Wiki 0.05
drug1828 Low Dose (10 mg) Control Wiki 0.05
drug2966 Sampling salivary Wiki 0.05
drug1244 FNC+Standard of Care Wiki 0.05
drug1456 Huaier Granule Wiki 0.05
drug1400 Helmet Continuous Positive Airway Pressure (CPAP) Wiki 0.05
drug3370 Tirofiban Injection Wiki 0.05
drug473 Blood sample and data record Wiki 0.05
drug2799 ResCure™ Wiki 0.05
drug3116 Standard Care Wiki 0.05
drug1195 Evaluation of clinical, instrumental and laboratory diagnostics tests Wiki 0.05
drug1029 Digital Health Online Platform Wiki 0.05
drug1595 Immunoglobulin of cured patients Wiki 0.05
drug1311 Fondaparinux Wiki 0.05
drug265 Aprepitant injectable emulsion Wiki 0.05
drug3631 Yinhu Qingwen Granula Wiki 0.05
drug3865 mavrilimumab Wiki 0.05
drug2166 Nitric Oxide-Sessions Wiki 0.05
drug1220 Exposure (not intervention) - SARS-CoV-2 infection Wiki 0.05
drug1845 Low flow ECMO driving by CVVH machine Wiki 0.05
drug1291 Fixed-duration higher dose Hydrocortisone Wiki 0.05
drug2475 Placebo EC-18 Wiki 0.05
drug982 Decitabine Wiki 0.05
drug3167 Standard treatment according to the Clinical protocols Wiki 0.05
drug3746 conventional oxygen Wiki 0.05
drug1072 Drug: NA-831 - 0.20 mg/kg Wiki 0.05
drug1686 Intubation Box Wiki 0.05
drug2296 Oral Wiki 0.05
drug3647 Zinc Sulfate Wiki 0.05
drug194 Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose Wiki 0.05
drug1772 Let It Out (LIO)-C Wiki 0.05
drug2806 Respiratory mechanics measurement Wiki 0.05
drug1368 Group1 Wiki 0.05
drug1591 Immunfluorescence Wiki 0.05
drug3074 Sodium Bicarbonate Wiki 0.05
drug318 Autologous Adipose MSC's Wiki 0.05
drug1680 Intravenous Immunoglobulin Wiki 0.05
drug650 CT score Wiki 0.05
drug3957 predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables? Wiki 0.05
drug3512 VC Wiki 0.05
drug3056 Single fraction whole lung radiotherapy Wiki 0.05
drug1039 Discontinuation of ACEi/ARB Wiki 0.05
drug2523 Placebo- 0.20 mg/kg Wiki 0.05
drug3178 Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki 0.05
drug1897 MSCs-derived exosomes Wiki 0.05
drug267 Arbidol Wiki 0.05
drug402 Bedside lung ultrasound Wiki 0.05
drug3366 Ticagrelor Wiki 0.05
drug2525 Placebo- 2.00 mg/kg Wiki 0.05
drug781 Clungene rapid test cassette Wiki 0.05
drug1859 Low-dose radiotherapy Wiki 0.05
drug2466 Placebo 0.20 mg + 2.00 mg/kg Wiki 0.05
drug2648 Pulmonary Physiotherapy Techniques Wiki 0.05
drug4019 specific exercise rehabilitation treatment Wiki 0.05
drug2713 RDV Wiki 0.05
drug2375 Pathogen-specific aAPC Wiki 0.05
drug1907 Macrolide administered for up to 14 days Wiki 0.05
drug3917 observation of covid 19 pneumonia Wiki 0.05
drug1738 Kukaa Salama: mHealth intervention Wiki 0.05
drug2357 PTSD Wiki 0.05
drug386 Bactek-R Wiki 0.05
drug1075 Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) Wiki 0.05
drug1166 Enoxaparin Wiki 0.05
drug2310 Ovotransferrin Wiki 0.05
drug1317 Fuzheng Huayu tablet Wiki 0.05
drug3425 Treamid Wiki 0.05
drug3673 alveolar recruitment Wiki 0.05
drug3627 Xiyanping injection Wiki 0.05
drug1823 Lopinavir/ritonavir treatment Wiki 0.05
drug2253 Occupational health workers Wiki 0.05
drug1385 HFNO Wiki 0.05
drug1730 Kamada Anti-SARS-CoV-2 Wiki 0.05
drug387 Bacterial species isolated Wiki 0.05
drug1712 Ivermectin 5 MG/ML oral solution, Dexamethasone 4-mg injection, Enoxaparin injection. Inpatient treatment with mechanical ventilation in ICU. Wiki 0.05
drug1933 Matching placebo Wiki 0.05
drug1060 Doxycyclin Wiki 0.05
drug2926 SOC + IFX-1 Wiki 0.05
drug1404 Heparin Wiki 0.05
drug115 ATYR1923 3 mg/kg Wiki 0.05
drug1214 Experimental Group Wiki 0.05
drug1415 High Flow Nasal Oxygen (HFNO) Wiki 0.05
drug953 DWJ1248 Wiki 0.05
drug2473 Placebo Control Wiki 0.05
drug2056 Multifrequency Bioimpedance Spectroscopy Wiki 0.05
drug1898 MSTT1041A Wiki 0.05
drug2465 Placebo 0.10 mg + 1.00 mg/kg Wiki 0.05
drug3768 eculizumab Wiki 0.05
drug697 Carotid Artery Reactivity Testing Wiki 0.05
drug965 Darunavir and Cobicistat Wiki 0.05
drug1844 Low dose whole lung radiotherapy for older patients with COVID-19 pneumonitis Wiki 0.05
drug1814 Lopinavir-Ritonavir Drug Combination Wiki 0.05
drug1880 MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg Wiki 0.05
drug3470 UCMSCs Wiki 0.05
drug2577 Prasugrel Hydrochloride 10 MG Oral Tablet Wiki 0.05
drug813 Combined use of a respiratory broad panel multiplex PCR and procalcitonin Wiki 0.05
drug902 Corticosteroid with or without colchicine Wiki 0.05
drug3966 pulmonary anomalies 4 months after documented COVID-19 pneumonia Wiki 0.05
drug3233 Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations) Wiki 0.05
drug1092 EG-HPCP-03a Wiki 0.05
drug771 Clinical, functional and radiological lung involvement evolution Wiki 0.05
drug3672 alpha1-proteinase inhibitor Wiki 0.05
drug4063 unfractionated heparin Wiki 0.05
drug878 Convalescent anti-SARS-CoV-2 plasma Wiki 0.05
drug2102 Nasal Brushing Wiki 0.05
drug3243 T89 Wiki 0.05
drug3932 oxyhydrogen Wiki 0.05
drug989 Degarelix Wiki 0.05
drug966 Darunavir/Cobicistat Wiki 0.05
drug2162 Nitric Oxide delivered via LungFit™ system Wiki 0.05
drug589 COVID-19 Convalscent Plasma Wiki 0.05
drug1843 Low dose radiation therapy Wiki 0.05
drug2675 Quantitative analysis of anti-SARS-CoV-2-antibodies Wiki 0.05
drug3024 Serology for Covid-19 Wiki 0.05
drug3870 mesenchymal stem cells Wiki 0.05
drug242 Antibiotics Wiki 0.05
drug1713 Ivermectin 5 mg/mL oral solution, Dexamethasone 4-mg injection, Aspirin 250 mg tablets Wiki 0.05
drug67 ACE Inhibitors and Calcium Channel Blockers Wiki 0.05
drug1720 Ivermectin and Doxycyline Wiki 0.05
drug556 CM4620-IE (Injectable Emulsion) Wiki 0.05
drug1749 LY3127804 Wiki 0.05
drug2655 Pulmonary ultrasound Wiki 0.05
drug3043 Shock-dependent hydrocortisone Wiki 0.05
drug602 COVID-19 Specific T Cell derived exosomes (CSTC-Exo) Wiki 0.05
drug3824 imaging, blood tests Wiki 0.05
drug2060 MuscleSound Ultrasound Wiki 0.05
drug2419 Phage Therapy Wiki 0.05
drug541 CAStem Wiki 0.05
drug1480 Hydroxychloroquine + lopinavir/ritonavir Wiki 0.05
drug2576 Prasugrel Wiki 0.05
drug337 Azithromycin 250 MG Wiki 0.05
drug2138 New screening strategy Wiki 0.05
drug1450 Hormones Wiki 0.05
drug506 Breath test Wiki 0.05
drug1065 Drug: GS-5734 - 1.00 mg/kg Wiki 0.05
drug643 CPAP Wiki 0.05
drug2737 Radiotherapy Wiki 0.05
drug3473 UNIKINON (Chloroquine phosphate) 200mg tablets Wiki 0.05
drug1340 Gas exchange measurement Wiki 0.05
drug248 Anticoagulant Therapy Wiki 0.05
drug1442 Home Sleep Apnea Testing or In-hospital Polysomnography Wiki 0.05
drug228 Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients Wiki 0.05
drug3935 patients receiving nasal high flow Wiki 0.05
drug856 Control arm Wiki 0.05
drug1339 Gargle/Mouthwash Wiki 0.05
drug2091 NP-120 (Ifenprodil) Wiki 0.05
drug3038 Sham Device Treatment Wiki 0.05
drug1763 Lanadelumab Wiki 0.05
drug286 Assessing antibody responses, neutralizing capacity and memory B-cell function Wiki 0.05
drug2348 PROTECTIVE VENTILATION Wiki 0.05
drug2694 Questionnaire including validated tools such as Patient Health Questionnaire (PHQ-9), the 7-item Generalised Anxiety Disorder (GAD- 7), the 7-item insomnia severity index Wiki 0.05
drug1811 Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki 0.05
drug126 AZD1656 Wiki 0.05
drug3831 inhaled type I interferon Wiki 0.05
drug1622 Infusion placebo Wiki 0.05
drug1584 Imaging by thoracic scanner Wiki 0.05
drug1840 Low dose Radiotherapy Wiki 0.05
drug26 150 ppm Nitric Oxide delivered through LungFit Delivery System Wiki 0.05
drug3474 UTTR1147A Wiki 0.05
drug2222 NuSepin® 0.1 mg Wiki 0.05
drug3475 UTTR1147A-matched Placebo Wiki 0.05
drug2321 Ozone auto-hemotherapy Wiki 0.05
drug3165 Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki 0.05
drug24 10% Povidone-iodine nasal decolonization swab plus 0.12% CHG oral rinse Wiki 0.05
drug363 BDB-001 Injection Wiki 0.05
drug1806 Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki 0.05
drug74 ACT-20-CM Wiki 0.05
drug755 Ciclesonide Inhalation Aerosol Wiki 0.05
drug4012 serum inflammatory biomarkers Wiki 0.05
drug237 Anti-SARS-CoV2 serological controls and serum neutralization Wiki 0.05
drug2445 Piperacillin-tazobactam Wiki 0.05
drug3504 Usual antibiotic treatment Wiki 0.05
drug1323 GC5131 Wiki 0.05
drug3082 Sofosbuvir and Ledipasvir Wiki 0.05
drug901 Corticosteroid injection Wiki 0.05
drug2519 Placebo solution Wiki 0.05
drug2758 Recombinant Human Interferon α2b Spray Wiki 0.05
drug3799 home spirometry Wiki 0.05
drug2204 Non-invasive red LLLT treatment to chest of patient. Wiki 0.05
drug132 Abidol Hydrochloride combined with Interferon atomization Wiki 0.05
drug240 Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients Wiki 0.05
drug521 Bromhexine Oral Tablet and/or hydroxychloroquine tablet Wiki 0.05
drug2225 Nursing care to reduce anxiety, fear and loneliness Wiki 0.05
drug1867 Lung Ultrasound Wiki 0.05
drug3283 Telehealth monitoring Wiki 0.05
drug170 Aerosol Box Wiki 0.05
drug301 Asunercept Wiki 0.05
drug2223 NuSepin® 0.2 mg Wiki 0.05
drug2542 Plasma from COVID-19 convalescent patient Wiki 0.05
drug3580 Vitamin E Wiki 0.05
drug266 Aprotinin Wiki 0.05
drug2390 Pectin Wiki 0.05
drug2431 Physical Therapy Exercise Wiki 0.05
drug2133 Neuromuscular Electrical Stimulation Wiki 0.05
drug741 Chloroquine Phosphate Tablets Wiki 0.05
drug1076 Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg) Wiki 0.05
drug2220 Novaferon Wiki 0.05
drug3720 cellulose-containing placebo capsules Wiki 0.05
drug2399 Pembrolizumab (MK-3475) Wiki 0.05
drug3383 Tocilizumab Injection [Actemra] Wiki 0.05
drug322 Auxora Wiki 0.05
drug1956 Mefloquine + azithromycin + / - tocilizumab Wiki 0.05
drug1955 Mefloquine Wiki 0.05
drug772 Clinical, laboratory and imaging characteristics of pneumonia Wiki 0.05
drug2833 Ritonavir/lopinavir Wiki 0.05
drug2560 Post-intensive Care unit syndrome Wiki 0.05
drug4014 severe covid-19 pneumonia with ET Wiki 0.05
drug3654 [18F]FP-R01-MG-F2 Wiki 0.05
drug1093 EG-HPCP-03a Placebo Wiki 0.05
drug934 Cyclosporin A Wiki 0.05
drug3379 Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA] Wiki 0.05
drug1588 Imatinib tablets Wiki 0.05
drug2533 Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells Wiki 0.05
drug2503 Placebo nebuliser solution Wiki 0.05
drug3141 Standard of Care (SOC) + ANG-3777 Wiki 0.05
drug82 ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS Wiki 0.05
drug2797 Repeat SARS-CoV-2 IgG antibodies at 45-65 days Wiki 0.05
drug3131 Standard administration of oxygen flow Wiki 0.05
drug740 Chloroquine Diphosphate Wiki 0.05
drug3797 high-titer anti-Sars-CoV-2 plasma Wiki 0.05
drug704 Ceftriaxone Wiki 0.05
drug2831 Ritonavir Wiki 0.05
drug2232 NİCaS Wiki 0.05
drug3693 biological assays in particular on the lipid metabolism Wiki 0.05
drug1280 FilmArray PCR on respiratory samples Wiki 0.05
drug344 Azithromycin with amoxicillin/clavulanate Wiki 0.05
drug1409 Heparin sodium Wiki 0.05
drug3926 oral polio vaccine + information Wiki 0.05
drug2535 Plaquenil 200Mg Tablet Wiki 0.05
drug1619 Informed consent Wiki 0.05
drug2698 Questionnaire-based observational study Wiki 0.05
drug873 Convalescent Plasma of patients with COVID-19 Wiki 0.05
drug191 Allogenic pooled olfactory mucosa-derived mesenchymal stem cells Wiki 0.05
drug2794 Remote pulmonary rehabilitation Wiki 0.05
drug2446 Piperacillin/tazobactam Wiki 0.05
drug2634 Protocolised mechanical ventilation strategy Wiki 0.05
drug637 COVID19 convalescent plasma infusion Wiki 0.05
drug991 Dental pulp mesenchymal stem cells Wiki 0.05
drug2129 NestaCell® Wiki 0.05
drug3374 Tociliuzumab Wiki 0.05
drug1185 Eritoran Wiki 0.05
drug239 Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients Wiki 0.05
drug2377 Patient Education Wiki 0.05
drug135 Acacia Senegal Wiki 0.05
drug1967 MenCare+/Bandebereho fathers'/couples' group education Wiki 0.05
drug1097 ELISA and Rapid test to detect antibodies against COVID-19 Wiki 0.05
drug1287 Five-days oseltamivir Wiki 0.05
drug1999 Methylprednisolone, Placebo Wiki 0.05
drug412 Best Available Therapy Wiki 0.05
drug2387 Patients admitted to Intensive Care Unit with SARS-CoV2 Wiki 0.05
drug2704 Quetiapine Wiki 0.05
drug1325 GLS-1027 Wiki 0.05
drug2098 Nafamostat Mesylate Wiki 0.05
drug1807 Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride Wiki 0.05
drug1352 Glycine Wiki 0.05
drug1034 Dipyridamole Wiki 0.05
drug2356 PTC299 Wiki 0.05
drug3202 Supine Positioning Wiki 0.05
drug3867 mechanical ventilation Wiki 0.05
drug3164 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki 0.05
drug3157 Standard screening strategy Wiki 0.05
drug1775 Levamisole Pill + Budesonide+Formoterol inhaler Wiki 0.05
drug182 AirGo Respiratory Monitor Wiki 0.05
drug108 ASC09F+Oseltamivir Wiki 0.05
drug75 ACT-20-MSC Wiki 0.05
drug1249 Face Mask + Soap Wiki 0.05
drug1745 LB1148 Wiki 0.05
drug1906 Macrolide administered for 3-5 days Wiki 0.05
drug530 Butterfly Wiki 0.05
drug546 CERC-002 Wiki 0.05
drug1066 Drug: GS-5734 - 2.00 mg/kg Wiki 0.05
drug3304 Ten-days oseltamivir Wiki 0.05
drug3685 avdoralimab Wiki 0.05
drug1882 MK-5475 Wiki 0.05
drug145 Acetylsalicylic acid Wiki 0.05
drug567 COVI-AMG Wiki 0.05
drug665 CYNK-001 Wiki 0.05
drug2598 Pro BNP , Vitamin D Wiki 0.05
drug1899 MSTT1041A-matched Placebo Wiki 0.05
drug4086 γ-Globulin Wiki 0.05
drug583 COVID-19 Androgen Sensitivity Test (CoVAST) Wiki 0.05
drug3530 Valproate Wiki 0.05
drug1248 FX06 Wiki 0.05
drug1842 Low dose radiation 35 cGy Wiki 0.05
drug1165 Enhanced hygiene measures Wiki 0.05
drug874 Convalescent SARS COVID-19 plasma Wiki 0.05
drug1694 Iota carrageenan nasal spray and Ivermectin oral drops (used as buccal drops) Wiki 0.05
drug2233 OCTAPLAS Wiki 0.05
drug3674 amoxicillin/clavulanate Wiki 0.05
drug2168 Nivolumab Wiki 0.05
drug2747 Rapid Pathogen Detection Wiki 0.05
drug1819 Lopinavir/Ritonavir + hydoxychloroquine Wiki 0.05
drug4033 standardized Lung Ultrasound (LUS) examination Wiki 0.05
drug80 AI model Wiki 0.05
drug2977 Scanning Chest X-rays and performing AI algorithms on images Wiki 0.05
drug1307 Follow-up of patients with COVID-19 Wiki 0.05
drug2052 Moxifloxacin or Levofloxacin Wiki 0.05
drug3123 Standard Of Care (SOC) + Placebo Wiki 0.05
drug2135 Neutral writing control Wiki 0.05
drug217 Angiography scanner Wiki 0.05
drug1567 Ibudilast Wiki 0.05
drug393 Baricitinib 4 MG Oral Tablet Wiki 0.05
drug3620 XAV-19 Wiki 0.05
drug1721 Ivermectin nasal Wiki 0.05
drug3163 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki 0.05
drug2697 Questionnaire, same tools as before, with inclusion of PCL5 questionnaire too. Wiki 0.05
drug114 ATYR1923 1 mg/kg Wiki 0.05
drug2771 Regadenoson Wiki 0.05
drug202 Amoxicillin-clavulanate Wiki 0.05
drug3146 Standard of care Wiki 0.05
drug3138 Standard of Care Wiki 0.05
drug1061 Doxycycline Wiki 0.05
drug879 Convalescent plasma Wiki 0.05
drug1000 Dexamethasone Wiki 0.05
drug3572 Vitamin C Wiki 0.04
drug2153 Nitazoxanide Wiki 0.04
drug3382 Tocilizumab Injection Wiki 0.04
drug3143 Standard of Care (SoC) Wiki 0.04
drug3337 Therapeutic anticoagulation Wiki 0.04
drug1872 M5049 Wiki 0.04
drug2649 Pulmonary Rehabilitation Wiki 0.04
drug2852 SAB-185 Wiki 0.04
drug890 Conventional treatment Wiki 0.04
drug1462 Human immunoglobulin Wiki 0.04
drug3059 Sirolimus Wiki 0.04
drug1831 Low Dose Radiotherapy Wiki 0.04
drug4070 venous ultrasound Wiki 0.04
drug166 Aerobic Exercise Training Wiki 0.04
drug1168 Enoxaparin 40 Mg/0.4 mL Injectable Solution Wiki 0.04
drug3144 Standard of Care Treatment Wiki 0.04
drug143 Acebilustat Wiki 0.04
drug3387 Tofacitinib 10 mg Wiki 0.04
drug2928 SOC + Placebo Wiki 0.04
drug3253 TD-0903 Wiki 0.04
drug577 COVID Convalescent Plasma Wiki 0.04
drug2873 SARS-CoV-2 diagnostic rapid test Wiki 0.04
drug1478 Hydroxychloroquine + azithromycin Wiki 0.04
drug1986 Metformin Wiki 0.04
drug3054 Simvastatin Wiki 0.04
drug3376 Tocilizumab (TCZ) Wiki 0.04
drug3690 basic treatment Wiki 0.04
drug1565 IVIG Wiki 0.04
drug424 Bevacizumab Injection Wiki 0.04
drug1998 Methylprednisolone Sodium Succinate Wiki 0.04
drug1486 Hydroxychloroquine 200 Mg Oral Tablet Wiki 0.04
drug900 Corticosteroid Wiki 0.04
drug2401 Pentoxifylline Wiki 0.04
drug2925 SOC Wiki 0.04
drug1970 Meplazumab for Injection Wiki 0.04
drug675 Canakinumab Wiki 0.04
drug1082 Duvelisib Wiki 0.04
drug2420 Phase 1 Wiki 0.04
drug3047 Siltuximab Wiki 0.04
drug1377 HB-adMSCs Wiki 0.04
drug2847 Ruxolitinib Wiki 0.03
drug205 Anakinra Wiki 0.03
drug2938 Saline Wiki 0.03
drug1705 Ivermectin Wiki 0.03
drug2536 Plasma Wiki 0.03
drug3819 hzVSF-v13 Wiki 0.03
drug935 Cyclosporine Wiki 0.03
drug236 Anti-SARS-CoV2 Serology Wiki 0.03
drug2941 Saline Placebo Wiki 0.03
drug642 COViage Wiki 0.03
drug2751 Ravulizumab Wiki 0.03
drug857 Control group Wiki 0.03
drug2421 Phase 2 Wiki 0.03
drug1607 Inactivated SARS-CoV-2 Vaccine (Vero cell) Wiki 0.03
drug1974 Mesenchymal Stromal Cells Wiki 0.03
drug2453 Placebo (Normal saline solution) Wiki 0.03
drug2340 PLACEBO Wiki 0.03
drug1467 Hydrocortisone Wiki 0.03
drug2141 Niclosamide Wiki 0.03
drug2099 Naltrexone Wiki 0.03
drug1640 Interferon beta-1a Wiki 0.03
drug478 Blood samples Wiki 0.03
drug864 Convalescent Plasma Wiki 0.03
drug3943 placebo Wiki 0.03
drug2782 Remdesivir Wiki 0.03
drug2621 Prone positioning Wiki 0.03
drug2313 Oxygen Wiki 0.03
drug2208 Normal Saline Wiki 0.03
drug2159 Nitric Oxide Wiki 0.03
drug1818 Lopinavir/Ritonavir Wiki 0.03
drug418 Best Supportive Care Wiki 0.03
drug2871 SARS-CoV-2 convalescent plasma Wiki 0.03
drug2723 RLS-0071 Wiki 0.03
drug2858 SARS-CoV-2 Wiki 0.03
drug1958 Melatonin Wiki 0.03
drug2097 Nafamostat Mesilate Wiki 0.02
drug2276 Online Survey Wiki 0.02
drug2284 Online survey Wiki 0.02
drug415 Best Practice Wiki 0.02
drug281 Aspirin Wiki 0.02
drug671 Camostat Wiki 0.02
drug587 COVID-19 Convalescent Plasma Wiki 0.02
drug2619 Prone position Wiki 0.02
drug2174 No intervention Wiki 0.02
drug2968 Sarilumab Wiki 0.02
drug739 Chloroquine Wiki 0.02
drug1334 Gam-COVID-Vac Wiki 0.02
drug481 Blood sampling Wiki 0.02
drug2685 Questionnaire Wiki 0.02
drug391 Baricitinib Wiki 0.02
drug2514 Placebo oral tablet Wiki 0.02
drug3132 Standard care Wiki 0.02
drug3702 blood sample Wiki 0.02
drug3502 Usual Care Wiki 0.02
drug472 Blood sample Wiki 0.02
drug3574 Vitamin D Wiki 0.02
drug2687 Questionnaire Administration Wiki 0.02
drug1492 Hydroxychloroquine Sulfate Wiki 0.02
drug791 Colchicine Wiki 0.01
drug3218 Survey Wiki 0.01
drug1262 Favipiravir Wiki 0.01

Correlated MeSH Terms (76)


Name (Synonyms) Correlation
D011024 Pneumonia, Viral NIH 0.46
D045169 Severe Acute Respiratory Syndrome NIH 0.16
D018352 Coronavirus Infections NIH 0.16
Name (Synonyms) Correlation
D053717 Pneumonia, Ventilator-Associated NIH 0.16
D017563 Lung Diseases, Interstitial NIH 0.13
D007249 Inflammation NIH 0.11
D012128 Respiratory Distress Syndrome, Adult NIH 0.09
D055371 Acute Lung Injury NIH 0.08
D013577 Syndrome NIH 0.08
D011020 Pneumonia, Pneumocystis NIH 0.07
D012127 Respiratory Distress Syndrome, Newborn NIH 0.07
D003141 Communicable Diseases NIH 0.06
D055370 Lung Injury NIH 0.06
D008171 Lung Diseases, NIH 0.06
D007239 Infection NIH 0.06
D012140 Respiratory Tract Diseases NIH 0.05
D001049 Apnea NIH 0.05
D001261 Pulmonary Atelectasis NIH 0.05
D011488 Protein Deficiency NIH 0.05
D011552 Pseudomonas Infections NIH 0.05
D001469 Barotrauma NIH 0.05
D015209 Cholangitis, Sclerosing NIH 0.05
D004646 Emphysema NIH 0.05
D004617 Embolism NIH 0.05
D018410 Pneumonia, Bacterial NIH 0.05
D000077299 Healthcare-Associated Pneumonia NIH 0.05
D016769 Embolism and Thrombosis NIH 0.05
D001768 Blister NIH 0.05
D007040 Hypoventilation NIH 0.05
D012120 Respiration Disorders NIH 0.05
D014115 Toxemia NIH 0.05
D053120 Respiratory Aspiration NIH 0.04
D013927 Thrombosis NIH 0.04
D011665 Pulmonary Valve Insufficiency NIH 0.04
D008173 Lung Diseases, Obstructive NIH 0.04
D030341 Nidovirales Infections NIH 0.04
D020181 Sleep Apnea, Obstructive NIH 0.04
D018805 Sepsis NIH 0.04
D000075902 Clinical Deterioration NIH 0.04
D003967 Diarrhea NIH 0.04
D012891 Sleep Apnea, NIH 0.04
D016470 Bacteremia NIH 0.04
D002761 Cholangitis NIH 0.04
D009410 Nerve Degeneration NIH 0.04
D054990 Idiopathic Pulmonary Fibrosis NIH 0.04
D012141 Respiratory Tract Infections NIH 0.03
D014777 Virus Diseases NIH 0.03
D004417 Dyspnea NIH 0.03
D009767 Obesity, Morbid NIH 0.03
D005355 Fibrosis NIH 0.03
D011251 Pregnancy Complications, Infectious NIH 0.03
D001987 Bronchiectasis NIH 0.03
D011654 Pulmonary Edema NIH 0.03
D000860 Hypoxia NIH 0.03
D020141 Hemostatic Disorders NIH 0.03
D011655 Pulmonary Embolism NIH 0.03
D001778 Blood Coagulation Disorders NIH 0.03
D016638 Critical Illness NIH 0.03
D060085 Coinfection NIH 0.03
D013923 Thromboembolism NIH 0.02
D007154 Immune System Diseases NIH 0.02
D003693 Delirium NIH 0.02
D009102 Multiple Organ Failure NIH 0.02
D003333 Coronaviridae Infections NIH 0.02
D009765 Obesity NIH 0.02
D008231 Lymphopenia NIH 0.02
D013313 Stress Disorders, Post-Traumatic NIH 0.02
D014947 Wounds and Injuries NIH 0.02
D006333 Heart Failure NIH 0.02
D012327 RNA Virus Infections NIH 0.02
D011248 Pregnancy Complications NIH 0.02
D007251 Influenza, Human NIH 0.02
D011658 Pulmonary Fibrosis NIH 0.01
D040921 Stress Disorders, Traumatic NIH 0.01
D009369 Neoplasms, NIH 0.01
D002318 Cardiovascular Diseases NIH 0.01

Correlated HPO Terms (28)


Name (Synonyms) Correlation
HP:0002090 Pneumonia HPO 0.99
HP:0006515 Interstitial pneumonitis HPO 0.13
HP:0002088 Abnormal lung morphology HPO 0.06
Name (Synonyms) Correlation
HP:0002104 Apnea HPO 0.05
HP:0002791 Hypoventilation HPO 0.05
HP:0100750 Atelectasis HPO 0.05
HP:0001907 Thromboembolism HPO 0.04
HP:0006536 Pulmonary obstruction HPO 0.04
HP:0010444 Pulmonary insufficiency HPO 0.04
HP:0100806 Sepsis HPO 0.04
HP:0002870 Obstructive sleep apnea HPO 0.04
HP:0030151 Cholangitis HPO 0.04
HP:0002014 Diarrhea HPO 0.04
HP:0002180 Neurodegeneration HPO 0.04
HP:0010535 Sleep apnea HPO 0.04
HP:0011947 Respiratory tract infection HPO 0.03
HP:0002098 Respiratory distress HPO 0.03
HP:0100598 Pulmonary edema HPO 0.03
HP:0002110 Bronchiectasis HPO 0.03
HP:0012418 Hypoxemia HPO 0.03
HP:0001928 Abnormality of coagulation HPO 0.03
HP:0002204 Pulmonary embolism HPO 0.03
HP:0001513 Obesity HPO 0.02
HP:0001888 Lymphopenia HPO 0.02
HP:0001635 Congestive heart failure HPO 0.02
HP:0002206 Pulmonary fibrosis HPO 0.01
HP:0002664 Neoplasm HPO 0.01
HP:0001626 Abnormality of the cardiovascular system HPO 0.01

Clinical Trials

Navigate: Correlations   HPO

There are 366 clinical trials


1 Treatment of Severe and Critical COVID-19 Pneumonia With Convalescent Plasma

Open label two arms, non randomized Convalescent Plasma treatment to severe and critical pneumonia COVID-19 hospitlaized patients compared to a historical cohort with matched controls.

NCT04432103
Conditions
  1. Covid-19
Interventions
  1. Biological: Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients
  2. Biological: Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients
MeSH:Pneumon Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: progression to critical stage

Measure: INCIDENCE OF CRITICAL PNEUMONIA

Time: 14 days after convalescent plasma administration

Description: mortality

Measure: MORTALITY RATE AMONG CRITICAL PNEUMONIA PATIENTS

Time: 28 days after convalescent plasma administration

Secondary Outcomes

Description: time to need mechanical ventilation

Measure: INCIDENCE OF MECHANICAL VENTILATION

Time: 14 days after convalescent plasma treatment

Description: time of mechanical ventilation needed

Measure: DAYS OF MECHANICAL VENTILATION

Time: 28 days after convalescent plasma treatment
2 Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia

REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia. In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19.

NCT02735707
Conditions
  1. Community-acquired Pneumonia, Influenza, COVID-19
Interventions
  1. Drug: Fixed-duration Hydrocortisone
  2. Drug: Shock-dependent hydrocortisone
  3. Drug: Ceftriaxone
  4. Drug: Moxifloxacin or Levofloxacin
  5. Drug: Piperacillin-tazobactam
  6. Drug: Ceftaroline
  7. Drug: Amoxicillin-clavulanate
  8. Drug: Macrolide administered for 3-5 days
  9. Drug: Macrolide administered for up to 14 days
  10. Drug: Five-days oseltamivir
  11. Drug: Ten-days oseltamivir
  12. Drug: Lopinavir/ritonavir
  13. Drug: Hydroxychloroquine
  14. Drug: Hydroxychloroquine + lopinavir/ritonavir
  15. Drug: Interferon-β1a
  16. Drug: Anakinra
  17. Drug: Fixed-duration higher dose Hydrocortisone
  18. Drug: Tocilizumab
  19. Drug: Sarilumab
  20. Drug: Vitamin C
  21. Drug: Therapeutic anticoagulation
  22. Drug: Simvastatin
  23. Biological: Convalescent plasma
  24. Other: Protocolised mechanical ventilation strategy
  25. Drug: Eritoran
  26. Drug: Apremilast
  27. Drug: Aspirin
  28. Drug: Clopidogrel
  29. Drug: Prasugrel
  30. Drug: Ticagrelor
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: All-cause mortality

Time: Day 90

Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection

Measure: Days alive and not receiving organ support in ICU

Time: Day 21

Secondary Outcomes

Measure: ICU Mortality

Time: Day 90

Measure: ICU length of stay

Time: Day 90

Measure: Hospital length of stay

Time: Day 90

Measure: Ventilator free days

Time: Day 28

Measure: Organ failure free days

Time: Day 28

Measure: All-cause mortality

Time: 6 months

Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)

Measure: Health-related Quality of life assessment

Time: 6 months

Measure: Proportion of intubated patients who receive a tracheostomy

Time: Day 28

Description: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital

Measure: Destination at time of hospital discharge

Time: Free text Day 90

Measure: Readmission to the index ICU during the index hospitalization

Time: Day 90

Measure: World Health Organisation 8-point ordinal scale outcome

Time: Hospital discharge

Other Outcomes

Description: Antibiotic Domain specific outcome

Measure: Occurrence of multi-resistant organism colonisation/infection

Time: Day 90, censored at hospital discharge

Description: Antibiotic Domain specific outcome

Measure: Occurrence clostridium difficile

Time: Day 90, censored at hospital discharge

Description: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.

Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death

Time: Day 90, censored at hospital discharge

Description: Antiviral Domain specific outcome. Only required at selected sites.

Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens

Time: Day 3, up to Day 7

Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint

Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing)

Time: Day 90, censored at hospital discharge
3 Detection of Integrin avb6 in Idiopathic Pulmonary Fibrosis, Primary Sclerosing Cholangitis, and Coronavirus Disease 2019 With [18F]FP-R01-MG-F2 With PET/CT

Detection of Integrin avb6 in Idiopathic Pulmonary Fibrosis, Primary Sclerosing Cholangitis, and Coronavirus Disease 2019 with [18F]FP-R01-MG-F2 with PET/CT

NCT03183570
Conditions
  1. Idiopathic Pulmonary Fibrosis
  2. Primary Sclerosing Cholangitis
  3. Covid19 Pneumonia
Interventions
  1. Drug: [18F]FP-R01-MG-F2
MeSH:Cholangitis Cholangitis, Sclerosing Pneumonia Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis
HPO:Cholangitis Pneumonia Pulmonary fibrosis

Primary Outcomes

Description: The SUVmax in a lung or liver with known IPF, COVID19 pneumonia, or PSC respectively will be compared to the SUVmax in a known healthy lung/liver. It is expected that the SUV max, which is a measurement of the maximum value of radiopharmaceutical uptake within the region of interest (ROI) in IPF, COVID19 pneumonia, and PSC will be higher than the SUV max in the healthy lung/liver.

Measure: SUV max comparison : IPF versus Healthy Lung, PSC versus Healthy Liver, COVID19 versus Healthy Lung

Time: an estimated average of 2 hours

Secondary Outcomes

Description: Blood samples for blood time-activity measurements taken at 1, 3, 5, 10, 30, and 60 minutes after tracer injection for tracer kinetic analysis. Tracer kinetic analysis shows radiopharmaceutical distribution from the blood to the tissues over time.

Measure: Time Activity Measurements

Time: an estimated average of 1 hours

Description: EKG data, vital signs and laboratory data collected before IV injection of [18F]FP-R01-MG-F2 and after completion of the scan will allow the investigators to evaluate the safety and tolerability of the radiopharmaceutical. This will be measured as the number of patients who successfully completed the study.

Measure: Incidence of Study Completion (Safety and Tolerability)

Time: an estimated average of 2 hours
4 SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia

In community acquired pneumonia, corticosteroids have been shown to have potential benefit. However, the limited and variable use of adjunctive corticosteroids in critically ill patients is largely due to an inability to identify patients that will benefit from the use of anti-inflammatory medications. This study compares usual care to a novel biomarker-tailored steroid dosing algorithm for patients with community acquired pneumonia. In April 2020, in response to the SARS CoV-2 pandemic, we added a COVID-19 arm to this study. The study will evaluate the role of biomarker-titrated adjuvant corticosteroid administration compared to usual care in patients admitted to hospital with SARS CoV-2 (COVID-19) infection and acute respiratory failure.

NCT03852537
Conditions
  1. Pneumonia
Interventions
  1. Drug: Methylprednisolone
  2. Other: Usual Care
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A percentage of eligible patients adhered to the timely initiation (within 12 hours of emergency room admission) and daily corticosteroid treatment according to ESICM/SCCM clinical practice guideline (control group) or biomarker concordance (intervention group)

Measure: Feasibility of the timely initiation of corticosteroids and implementation of biomarker-titrated corticosteroid dosing: percentage of eligible patients adhered to the timely initiation

Time: Within 30 days of enrollment in study.

Secondary Outcomes

Description: Death from any cause

Measure: Mortality

Time: Within 30 days and 90 days of study enrollment

Description: Progression of disease is defined by the need for high flow nasal cannula oxygen, noninvasive or invasive ventilation. Given the proliferation of high flow nasal cannula oxygen use in lieu of mechanical ventilation, instead of ventilator-free days the investigators opt for using advanced respiratory support free days where "advanced respiratory support" includes both invasive and noninvasive mechanical ventilation and the high flow nasal cannula oxygen.

Measure: Progression of disease

Time: Within hospitalization or 30 days of study enrollment (whichever is sooner)

Description: Measured by respiratory component of SOFA at time of ICU admission, after 24 hours, after 48 hours and after 72 hours and by the organ failure free days. In the absence of daily arterial blood gas analysis, PaO2/FiO2 ratio will be replaced by SpO2/FiO2 ratio

Measure: Evolution of respiratory failure

Time: Within 72 hours of enrollment in study.

Description: Assessed by renal component of Sequential Organ Failure Assessment (SOFA) Score score. This is a scale from 0-4 (with 0 indicating no renal failure and 4 indicating severe renal failure).

Measure: Evolution of kidney failure

Time: Within 72 hours of enrollment in study.

Description: Assessed by cardiac component of Sequential Organ Failure Assessment (SOFA) Score score. This is a scale from 0-4 (with 0 indicating no cardiovascular failure and 4 indicating severe cardiovascular failure).

Measure: Evolution of shock

Time: Within 72 hours of enrollment in study.

Description: In hospital and in ICU

Measure: Length of stay

Time: From time of study enrollment up to discharge from hospital, to a maximum of 1 year.

Description: Number of participants who have hyperglycemia while receiving corticosteroids. Hyperglycemia is defined as a consistently elevated blood sugar level requiring insulin administration.

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Hyperglycemia

Time: Up to day +5 following study enrollment.

Description: Number of participants who develop delirium while receiving corticosteroids. Delirium will be assessed by Confusion Assessment Method for the ICU (CAM-ICU) measurement tool. The CAM-ICU is a binary (yes/no) scale for assessing the presence of delirium.

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Delirium

Time: Up to day +5 following study enrollment.

Description: Number of participants who develop secondary infections during and after steroid therapy. A secondary infection is defined as a new infection that develops after initiation of corticosteroid therapy, until 5 days after steroids are discontinued.

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Secondary Infection

Time: Up to day +14 following study enrollment.
5 RASCALS: Rapid Assay for Sick Children With Acute Lung Infection Study

Lower Respiratory Tract infections are a common cause of admission to the intensive care unit. Children routinely receive antibiotics until the tests confirm whether the infection is bacterial or viral. The exclusion of bacterial infection may take 48 hours or longer for culture tests on biological samples to be completed. In many cases, the results may be inconclusive or negative if the patient has already received antibiotics prior to the sample being taken. A rapid assay to detect the most likely cause of infection could improve the speed with which antibiotic therapy is rationalised or curtailed. This study aims to assess whether a new genetic testing kit which can identify the presence of bacteria and viruses within hours rather than days is a feasible tool in improving antibiotic prescribing and rationalisation of therapy in critically ill children with suspected lower respiratory tract infection.

NCT04233268
Conditions
  1. Lower Respiratory Tract Infection
  2. Ventilator Associated Pneumonia
  3. COVID19
Interventions
  1. Diagnostic Test: Rapid Pathogen Detection
MeSH:Infection Communicable Diseases Respiratory Tract Infections Pneumonia, Ventilator-Associated Pneumonia
HPO:Pneumonia Respiratory tract infection

Primary Outcomes

Description: Performance of novel pathogen detection assays compared to standard microbiology, in regard to sensitivity, specificity and likelihood ratios

Measure: Performance of the novel pathogen detection assay

Time: 3 years

Secondary Outcomes

Description: Time to reportable test results

Measure: Time to results

Time: 3 years

Description: Where routine culture is negative, what proportion of tests have a positive detection using the novel assay?

Measure: Negative cultures

Time: 3 years

Description: Duration of therapy and number of antibiotic classes during paediatric intensive care unit admission

Measure: Antibiotic therapy

Time: 3 years

Description: Number of critically ill children requiring mechanical ventilation with COVID19 compared to those without

Measure: Prevalence of COVID19 in children admitted to PICU

Time: 2 years
6 Effects of Traditional Chinese Medicines (TCMs) on Patients With COVID-19 Infection: A Perspective, Open-labeled, Randomized, Controlled Trial

The aim of this study is to test whether Traditional Chinese Medicines (TCMs) are effective and safe for treating COVID-19 infection. After the enrolment of approximately 30 subjects, the recruitment will be paused, and planned interim analysis will be performed to preliminarily investigate the efficacy and safety of TCMs in patients infected with COVID-19.

NCT04251871
Conditions
  1. Pneumonia Caused by Human Coronavirus (Disorder)
Interventions
  1. Drug: Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules
  2. Drug: Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir)
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The incidence rate of acute respiratory distress syndrome (ARDS) development

Measure: The incidents of acute respiratory distress syndrome (ARDS) development

Time: 14 days

Secondary Outcomes

Description: Time to complete remission of fever in eligible subjects

Measure: The time to fever resolution rate

Time: 14 days

Description: improvement of chest radiographic evidence indirectly reflects recovery in patients infected with COVID-19.

Measure: Time to recovery of lung injury

Time: 14 days

Other Outcomes

Description: The rate of subject who die will be described.

Measure: Rate of subjects who die

Time: 28 days

Description: The rate of subjects with severe 2019-nCoV infection who receive systematic corticosteroids will be described.

Measure: Rate of subjects receiving systematic corticosteroids

Time: 28 days

Description: The length of hospital stays

Measure: The length of hospital stays

Time: 28 days

Description: The duration of respiratory support including invasive and non-invasive mechanical ventilation

Measure: The duration of respiratory support

Time: 28 days
7 Safety and Efficiency of Mesenchymal Stem Cell in Treating Pneumonia Patients Infected With COVID-19

The SARS-CoV-2 infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. There is no confirmed antivirus therapy for people infected SARS-CoV-2, most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Mesenchymal Stem Cells (MSCs) therapy for pneumonia patients infected with SARS-CoV-2.

NCT04252118
Conditions
  1. COVID-19
Interventions
  1. Biological: MSCs
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of Pneumonia Improvement

Measure: Size of lesion area by chest radiograph or CT

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21,Day 28

Description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Measure: Side effects in the MSCs treatment group

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

Secondary Outcomes

Description: Evaluation of Pneumonia Improvement

Measure: Improvement of Clinical symptoms including duration of fever and respiratory

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28

Description: Marker for COVID-19

Measure: Time of nucleic acid turning negative

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

Description: Marker for efficacy of treatment

Measure: Rate of mortality within 28-days

Time: Day 28

Description: Marker of Immunological function

Measure: CD4+ and CD8+ T celll count

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

Description: Markers of organ function

Measure: Alanine aminotransferase

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

Description: Markers of Infection

Measure: C-reactive protein

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

Description: Markers of organ function

Measure: Creatine kinase

Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180
8 Efficacy and Safety of Darunavir and Cobicistat for Treatment of COVID-19

The study aims to evaluate the efficacy and safety of darunavir and cobistastat in the treatment of COVID-19 pneumonia

NCT04252274
Conditions
  1. Pneumonia, Pneumocystis
  2. Coronavirus
Interventions
  1. Drug: Darunavir and Cobicistat
MeSH:Pneumonia, Pneumocystis Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 7

Time: 7 days after randomization

Secondary Outcomes

Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 3

Time: 3 days after randomization

Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 5

Time: 5 days after randomization

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Time: 14 days after randomization

Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.

Measure: The critical illness rate of subjects at weeks 2

Time: 14 days after randomization

Measure: The mortality rate of subjects at weeks 2

Time: 14 days after randomization
9 An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Two Therapeutic Schemes(Abidol Hydrochloride,Abidol Hydrochloride Combined With Interferon Atomization)in the Treatment of 2019-nCoV Pneumonia.

At present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of two therapeutic schemes(abidol hydrochloride,abidol hydrochloride combined with interferon atomization)in the treatment of 2019-nCoV viral pneumonia, so as to provide reliable evidence-based medicine for the treatment of viral pneumonia caused by 2019-nCoV.

NCT04254874
Conditions
  1. 2019-nCoV
Interventions
  1. Drug: Abidol hydrochloride
  2. Drug: Abidol Hydrochloride combined with Interferon atomization
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A: For mild patients : fever, cough and other symptoms relieved with improved lung CT; B:For severe patients : fever, cough and other symptoms relieved with improved lung CT,SPO2> 93% or PaO2/FiO2> 300mmHg (1mmHg=0.133Kpa);

Measure: Rate of disease remission

Time: two weeks

Description: Compare the average time of lung imaging recovery after 2 weeks of treatment in each group.

Measure: Time for lung recovery

Time: two weeks

Secondary Outcomes

Measure: Rate of no fever

Time: two weeks

Measure: Rate of respiratory symptom remission

Time: two weeks

Measure: Rate of lung imaging recovery

Time: two weeks

Measure: Rate of CRP,ES,Biochemical criterion (CK,ALT,Mb)recovery

Time: two weeks

Measure: Rate of undetectable viral RNA

Time: two weeks
10 An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Three Antiviral Drugs(Abidol Hydrochloride, Oseltamivir and Lopinavir/Ritonavir) in the Treatment of 2019-nCoV Pneumonia.

At present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of three antiviral drugs in the treatment of 2019-nCoV pneumonia by studying the efficacy of abidol hydrochloride, oseltamivir and lopinavir/ritonavir in the treatment of 2019-nCoV viral pneumonia, and to explore effective antiviral drugs for new coronavirus. To provide reliable evidence-based medicine basis for the treatment of viral pneumonia caused by new coronavirus infection.

NCT04255017
Conditions
  1. 2019-nCoV
Interventions
  1. Drug: Abidol hydrochloride
  2. Drug: Oseltamivir
  3. Drug: Lopinavir/ritonavir
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A: For mild patients : fever, cough and other symptoms relieved with improved lung CT; B:For severe patients : fever, cough and other symptoms relieved with improved lung CT,SPO2> 93% or PaO2/FiO2>300mmHg (1mmHg=0.133Kpa);

Measure: Rate of disease remission

Time: two weeks

Description: Compare the average time of lung imaging recovery after 2 weeks of treatment in each group.

Measure: Time for lung recovery

Time: two weeks

Secondary Outcomes

Measure: Rate of no fever

Time: two weeks

Measure: Rate of respiratory symptom remission

Time: two weeks

Measure: Rate of lung imaging recovery

Time: two weeks

Measure: Rate of CRP,ES,Biochemical criterion(CK,ALT,Mb) recovery

Time: two weeks

Measure: Rate of undetectable viral RNA

Time: two weeks
11 A Survey of Psychological Status of Medical Workers and Residents in the Context of 2019 Novel Coronavirus Pneumonia in Wuhan, China

Due to the outbreak of 2019 Novel Coronavirus Pneumonia in Wuhan, Hubei province, medical staff and residents are facing great psychological pressure, the investigator plan to use electronic questionnaire to carry out investigation research.

NCT04260308
Conditions
  1. Virus; Pneumonia
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: GHQ-12(general health questionnaire-12): minimal score 0, maximal score 12, higher scores mean a better or worse outcome.

Measure: GHQ-12(general health questionnaire-12)

Time: 2 weeks

Secondary Outcomes

Description: IES-R(Impact of Event Scale-Revised):score range:0-88, the higher the worse

Measure: IES-R(Impact of Event Scale-Revised)

Time: 2 weeks
12 Randomized, Open, Multicenter Study on the Efficacy and Safety of Arbidol Hydrochloride Tablets in Treating Pneumonia in Patients Infected With Novel Coronavirus (2019-ncov).

In the absence of 2019-ncov specific therapeutic drugs, arbidol is effective against a variety of coronaviruses in vitro pharmacodynamics. In order to observe the efficacy and safety of arbidol in the treatment of 2019-ncov infected pneumonia, this study is planned.

NCT04260594
Conditions
  1. 2019-nCoV
Interventions
  1. Drug: Arbidol
  2. Other: basic treatment
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Virus negative conversion rate in the first week

Time: first week

Secondary Outcomes

Description: virus negative conversion rate in second week, overall virus negative conversion rate

Measure: Virus negative conversion rate

Time: 14-20 days

Description: defined as: the rate of Axillary temperature ≤37.5 ℃ for at least 48h

Measure: Antipyretic rate

Time: 14-20 days

Description: time to relieve symptoms of fever, cough, dyspnea, myalgia, etc

Measure: Symptom relief time

Time: 14-20 days

Description: no adjuvant oxygen therapy, resting oxygen saturation>95%, oxygenation index>350

Measure: Finger oxygen improvement rate

Time: 14-20 days

Description: Mild, common type progression to severe or critical illness rate

Measure: Disease progression rate

Time: 14-20 days

Measure: Mortality rate

Time: 14-20 days

Measure: Incidence of severe adverse reactions

Time: 14-20 days

Measure: Change curve of peripheral blood lymphocyte count

Time: 14-20 days
13 A Randomized,Open,Controlled Small Sample Clinical Study to Evaluate the Efficacy and Safety of ASC09/Ritonavir Compound Tablets and Ritonavir for 2019-nCoV Pneumonia

Based on oseltamivir treatment, evaluate the efficacy and safety of ASC09/ritonavir compound tablets(ASC09F) or ritonavir tablets for 2019-nCoV infection patients.

NCT04261270
Conditions
  1. 2019-nCoV Pneumonia
Interventions
  1. Drug: ASC09F+Oseltamivir
  2. Drug: Ritonavir+Oseltamivir
  3. Drug: Oseltamivir
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The definition of comprehensive adverse outcome is as follows: SPO2≤93% without oxygen inhalation; PaO2/FiO2≤300mmHg; RR≥30 bpm without oxygen inhalation.

Measure: Rate of comprehensive adverse outcome

Time: 14 days

Secondary Outcomes

Description: The definition of clinical remission: Based on the symptoms of the disease (fever,cough,diarrhea,myalgia,dyspnea) has been relieved for 48 hours; There is no evidence of disease progression(New dyspnea, SpO2 decreased≥3%,RR≥30 bpm without oxygen inhalation).

Measure: Time of clinical remission

Time: 28 days

Measure: Rate of no fever

Time: 14 days

Measure: Rate of no cough

Time: 14 days

Measure: Rate of no dyspnea

Time: 14 days

Measure: Rate of no need for oxygen inhalation

Time: 14 days

Measure: Rate of undetectable viral RNA

Time: 14 days

Measure: Rate of mechanical ventilation

Time: 28 days

Measure: Rate of ICU admission

Time: 28 days

Measure: Rate and time of CRP,ES,Biochemical criterion(CK,ALT,Mb)recovery

Time: 28 days
14 A Randomized, Open-label, Controlled, Single-center Study to Evaluate the Efficacy of Intravenous Immunoglobulin Therapy in Patients With Severe 2019- nCoV Pneumonia

In this single-center, randomized, open-label, controlled study, the investigators will evaluate the efficacy and safety of Intravenous Immunoglobulin (IVIG) in combination with standard care for severe 2019 novel coronavirus (2019-nCoV) pneumonia.

NCT04261426
Conditions
  1. 2019-nCoV
Interventions
  1. Drug: Intravenous Immunoglobulin
  2. Other: Standard care
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).

Measure: Clinical improvement based on the 7-point scale

Time: 28 days after randomization

Description: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.

Measure: Lower Murray lung injury score

Time: 7 days after randomization

Description: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.

Measure: Lower Murray lung injury score

Time: 14 days after randomization

Secondary Outcomes

Description: Number of deaths during study follow-up

Measure: 28-day mortality

Time: Measured from Day 0 through Day 28

Description: Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.

Measure: Duration of mechanical ventilation

Time: Measured from Day 0 through Day 28

Description: Days that a participant spent at the hospital. Multiple hospitalizations are summed up.

Measure: Duration of hospitalization

Time: Measured from Day 0 through Day 28

Description: Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples.

Measure: Proportion of patients with negative RT-PCR results

Time: 7 and 14 days after randomization

Description: Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).

Measure: Proportion of patients in each category of the 7-point scale

Time: 7,14 and 28 days after randomization

Description: Proportion of patients with different inflammation factors in normalization range.

Measure: Proportion of patients with normalized inflammation factors

Time: 7 and 14 days after randomization

Description: Frequency of Adverse Drug Events

Measure: Frequency of Adverse Drug Events

Time: Measured from Day 0 through Day 28

Description: Frequency of Serious Adverse Drug Events

Measure: Frequency of Serious Adverse Drug Events

Time: Measured from Day 0 through Day 28
15 Efficacy and Safety of Hydroxychloroquine for Treatment of COVID-19

The study aims to evaluate the efficacy and safety of hydroxychloroquine in the treatment of COVID-19 pneumonia.

NCT04261517
Conditions
  1. Pneumonia, Pneumocystis
  2. Coronavirus
  3. COVID-19
Interventions
  1. Drug: Hydroxychloroquine
MeSH:Pneumonia, Pneumocystis Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 3

Time: 3 days after randomization

Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 5

Time: 5 days after randomization

Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 7

Time: 7 days after randomization

Measure: The mortality rate of subjects at weeks 2

Time: 14 days after randomization

Secondary Outcomes

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Time: 14 days after randomization

Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.

Measure: The critical illness rate of subjects at weeks 2

Time: 14 days after randomization
16 An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Different Hormone Doses in the Treatment of 2019-nCoV Severe Pneumonia

At present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of different hormone doses in the treatment of 2019-nCoV severe Pneumonia.This study explores effective treatment programs for 2019-nCoV severe pneumonia and provides a reliable evidence-based basis for the treatment.

NCT04263402
Conditions
  1. 2019-nCoV Severe Pneumonia
Interventions
  1. Drug: Methylprednisolone
  2. Drug: Methylprednisolone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: For mild patients: disease remission refers to relieved symptoms with improved lung CT; For severe patients: disease remission refers to relieved symptoms with improved lung CT; or SPO2>93% or PaO2/FiO2 >300mmHg.

Measure: Rate of disease remission

Time: day 7

Description: the critical stage refers to respiratory failure that occurs and requires mechanical ventilation, shock, or having other organ failure that needs ICU monitoring and treatment.

Measure: Rate and time of entering the critical stage

Time: day 7

Secondary Outcomes

Description: Rate of patients without fever at day 7

Measure: Rate of normal tempreture

Time: day 7

Description: Rate of patients with respiratory symptom remission at day 7

Measure: Rate of respiratory symptom remission

Time: day 7

Description: Rate of patients with lung imaging recovery at day 7

Measure: Rate of lung imaging recovery

Time: day 7

Description: Rate of patients with laboratory indicator recovery at day 7

Measure: Rate of laboratory indicator recovery

Time: day 7

Description: Rate of patients withundetectable viral RNA at day 7

Measure: Rate of undetectable viral RNA

Time: day 7
17 Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia: a Prospective Randomized Clinical Trial

2019 new coronavirus (2019-nCoV) infected pneumonia, namely severe acute respiratory infection (SARI) has caused global concern and emergency. There is a lack of effective targeted antiviral drugs, and symptomatic supportive treatment is still the current main treatment for SARI. Vitamin C is significant to human body and plays a role in reducing inflammatory response and preventing common cold. In addtion, a few studies have shown that vitamin C deficiency is related to the increased risk and severity of influenza infections. We hypothize that Vitamin C infusion can help improve the prognosis of patients with SARI. Therefore, it is necessary to study the clinical efficacy and safety of vitamin C for the clinical management of SARI through randomized controlled trials during the current epidemic of SARI.

NCT04264533
Conditions
  1. Vitamin C
  2. Pneumonia, Viral
  3. Pneumonia, Ventilator-Associated
Interventions
  1. Drug: VC
  2. Drug: Sterile Water for Injection
MeSH:Pneumonia, Ventilator-Associated Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: days without ventilation support during 28 days after patients' enrollment

Measure: Ventilation-free days

Time: on the day 28 after enrollment

Secondary Outcomes

Description: wether the patient survives

Measure: 28-days mortality

Time: on the day 28 after enrollment

Description: days of the patients staying in the ICU

Measure: ICU length of stay

Time: on the day 28 after enrollment

Description: the rate of CPR

Measure: Demand for first aid measuments

Time: on the day 28 after enrollment

Description: days of using vasopressors

Measure: Vasopressor days

Time: on the day 28 after enrollment

Description: P O2/Fi O2 which reflects patients' respiratory function

Measure: Respiratory indexes

Time: on the day 10 and 28 after enrollment

Description: Ecmo or ventilator

Measure: Ventilator parameters

Time: on the day 10 and 28 after enrollment

Description: Acute Physiology and Chronic Health Evaluation

Measure: APACHE II scores

Time: on the day 10 after enrollment

Description: Sepsis-related Organ Failure Assessment

Measure: SOFA scores

Time: on the day 10 after enrollment
18 An Exploratory Clinical Study on the Treatment of Acute Severe 2019-nCoV Pneumonia With Immunoglobulin From Cured 2019-nCoV Pneumonia Patients

The new coronavirus pneumonia is an acute infectious pneumonia. The pathogen is a previously unknown new coronavirus, namely 2019 new coronavirus (2019 novel coronavirus, 2019 nCoV). However, there is no specific anti-viral drug. It has been found that the specific antibodies against virus antigen are produced after these patients were cured, which could block the infection of 2019 nCoV on the host cells. At present, immunoadsorption is the most direct, rapid and effective method to separate immunoglobulin from the cured patients. Therefore, the study aims to prepare the immunoglobulin from 2019-ncov pneumonia cured patients, evaluate the efficacy and safety of the immunoglobulin in 2019-ncov pneumonia cured patients on the treatment of acute severe 2019-ncov pneumonia, and provide a new strategy for the treatment of 2019-ncov pneumonia.

NCT04264858
Conditions
  1. 2019-nCoV
  2. Immunoglobulin of Cured Patients
Interventions
  1. Drug: Immunoglobulin of cured patients
  2. Drug: γ-Globulin
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: TTCI is defined as the time (in days) from initiation of study treatment (active or placebo) until a decline of two categories from admission status on a six-category ordinal scale of clinical status which ranges from 1 (discharged) to 6 (death). Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.

Measure: Time to Clinical Improvement (TTCI)

Time: up to 28 days

Secondary Outcomes

Description: on days 7, 14, 21, and 28

Measure: Clinical status assessed by the ordinal scale

Time: up to 28 days

Description: 1. No need for supplemental oxygenation; 2. nasal cathete oxygen inhalation;3. Mask oxygen inhalation;4. Noninvasive ventilator oxygen supply;5. Invasive ventilator oxygen supply.

Measure: The differences in oxygen intake methods

Time: up to 28 days

Measure: Duration (days) of supplemental oxygenation

Time: up to 28 days

Measure: Duration (days) of mechanical ventilation

Time: up to 28 days

Measure: The mean PaO2/FiO2

Time: up to 28 days

Description: The detection frequency could be increased according to clinician's decision

Measure: The lesions of the pulmonary segment numbers involved in pulmonary CT [ every 7 days]

Time: up to 28 days

Measure: Time to 2019-nCoV RT-PCR negativity in respiratory tract specimens [every 3 days]

Time: up to 28 days

Description: The antibody titer is detected on days 3 and 28

Measure: Dynamic changes of 2019-nCoV antibody titer in blood

Time: up to 28 days

Measure: Length of hospital stay (days)

Time: up to 28 days

Measure: All cause mortality

Time: up to 28 days
19 Clinical Research Regarding the Availability and Safety of UC-MSCs Treatment for Serious Pneumonia and Critical Pneumonia Caused by the 2019-nCOV Infection

Serious Pneumonia and Critical Pneumonia caused by the 2019-nCOV infection greatly threats patients' life, UC-MSCs treatment has been proved to play a role in curing multiple diseases. And this study is conducted to find out whether or not it will function in 2019-nCOV infection Pneumonia.

NCT04269525
Conditions
  1. Pneumonia, Viral
  2. Pneumonia, Ventilator-Associated
Interventions
  1. Biological: UC-MSCs
MeSH:Pneumonia, Ventilator-Associated Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: partial arterial oxygen pressure (PaO2) / oxygen concentration (FiO2)

Measure: Oxygenation index

Time: on the day 14 after enrollment

Secondary Outcomes

Description: whether the patient survives

Measure: 28 day mortality

Time: on the day 28 after enrollment

Description: days of the patients in hospital

Measure: Hospital stay

Time: up to 6 months

Description: whether or not the 2019-nCoV antibody is positive

Measure: 2019-nCoV antibody test

Time: on the day 7,14,28 after enrollment

Description: whether or not the 2019-nCoV nucleic acid test is positive

Measure: 2019-nCoV nucleic acid test

Time: on the day 7,14,28 after enrollment

Description: whether lung imaging examinations show the improvement of the pneumonia

Measure: Improvement of lung imaging examinations

Time: on the day 7,14,28 after enrollment

Description: counts of white blood cell in a litre of blood

Measure: White blood cell count

Time: on the day 7,14,28 after enrollment

Description: counts of lymphocyte in a litre (L) of blood

Measure: Lymphocyte count

Time: on the day 7,14,28 after enrollment

Description: procalcitonin in microgram(ug)/L

Measure: Procalcitonin

Time: on the day 7,14,28 after enrollment

Description: IL-2 in picogram(pg)/millilitre(mL)

Measure: interleukin(IL)-2

Time: on the day 7,14,28 after enrollment

Description: IL-4 in pg/mL

Measure: IL-4

Time: on the day 7,14,28 after enrollment

Description: IL-6 in pg/mL

Measure: IL-6

Time: on the day 7,14,28 after enrollment

Description: IL-10 in pg/mL

Measure: IL-10

Time: on the day 7,14,28 after enrollment

Description: TNF-α in nanogram(ng)/L

Measure: tumor necrosis factor(TNF)-α

Time: on the day 7,14,28 after enrollment

Description: γ-IFN in a thousand unit (KU)/L

Measure: γ-interferon(IFN)

Time: on the day 7,14,28 after enrollment

Description: CRP in microgram(μg)/L

Measure: C-reactive protein(CRP)

Time: on the day 7,14,28 after enrollment

Description: counts of CD4+ T-Lymphocytopenia in litre

Measure: CD4+ T-Lymphocytopenia

Time: on the day 7,14,28 after enrollment

Description: counts of CD8+ T-Lymphocytopenia in a litre

Measure: CD8+ T-Lymphocytopenia

Time: on the day 7,14,28 after enrollment

Description: counts of NK in a litre

Measure: natural killer cell(NK)

Time: on the day 7,14,28 after enrollment
20 Efficacy and Safety of Corticosteroids in COVID-19: A Prospective Randomized Controlled Trails

There is still controversy about the effective of glucocorticoids for the treatment of novel coronavirus pneumonia. This is a prospective randomized controlled trails. The aim is to explore the effectiveness and safety of glucocorticoids in the treatment of novel coronavirus pneumonia.

NCT04273321
Conditions
  1. COVID-19
  2. Novel Coronavirus Pneumonia
Interventions
  1. Drug: Methylprednisolone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The clinical symptoms and signs continue to deteriorate, or new pulmonary or extrapulmonary lesions appear, or the chest imaging indicates the progress, and the patient is transferred to ICU or intubation and invasive ventilation or died.

Measure: the incidence of treatment failure in 14 days

Time: 14 days

Secondary Outcomes

Description: The clinical symptoms and signs improved or alleviated (the temperature be normal , respiratory symptoms improved significantly, imaging showed obvious absorption) and no additional or alternative treatment was needed.

Measure: clinical cure incidence in 14 days

Time: 14 days

Description: the duration from admission to virus negative

Measure: the duration of virus change to negative

Time: 30 days

Description: the patient die in 30 days

Measure: mortality at day 30

Time: 30 days

Description: the patients transform to ICU because of clinical deteriorate in 30 days

Measure: ICU admission rate in 30 days

Time: 30 days
21 The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia: a Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study

In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Thalidomide has anti-inflammatory, anti-fibrotic, anti-angiogenesis, and immune regulation effects. This study is the first Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study at home and abroad to use immunomodulators to treat patients with COVID-19 infection.

NCT04273529
Conditions
  1. COVID-19 Thalidomide
Interventions
  1. Drug: thalidomide
  2. Drug: placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours. Normalisation and alleviation criteria: Fever - ≤36.6°C or -axilla, ≤37.2 °C oral or ≤37.8°C rectal or tympanic, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.

Measure: Time to Clinical recoveryTime to Clinical Recovery (TTCR)

Time: up to 28 days

Secondary Outcomes

Description: baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen

Measure: All cause mortality

Time: up to 28 days

Description: Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.

Measure: Frequency of respiratory progression

Time: up to 28 days

Description: in those with fever at enrolment

Measure: Time to defervescence

Time: up to 28 days

Other Outcomes

Description: in those with cough at enrolment rated severe or moderate

Measure: Time to cough reported as mild or absent

Time: up to 28 days

Description: patients with moderate / severe dyspnea when enrolled

Measure: Respiratory improvement time

Time: up to 28 days

Measure: Frequency of requirement for supplemental oxygen or non-invasive ventilation

Time: up to 28 days

Measure: Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen

Time: up to 28 days

Measure: Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve

Time: up to 28 days

Measure: Frequency of requirement for mechanical ventilation

Time: up to 28 days

Measure: Frequency of serious adverse events

Time: up to 28 days

Measure: Serum TNF-α, IL-1β, IL-2, IL-6, IL-7, IL-10, GSCF, IP10,MCP1, MIP1α and other cytokine expression levels before and after treatment

Time: up to 28 days
22 Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19

The novel coronavirus pneumonia is a kind of new emerging respiratory infectious disease, characterized by fever, dry cough, and chest tightness, and caused by the infection of the 2019 novel coronavirus (2019-nCoV). In severe cases, there will be rapid respiratory system failure. The novel coronavirus pneumonia is extremely contagious and the disease progresses rapidly. It has become a urgent and serious public health event that threatens human life and health globally. Among them, severe pneumonia caused by novel coronavirus is characterized by extensive acute inflammation of the lungs and the patient is critically ill. At present, there is no effective treatment in clinical practice.Most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for severe pneumonia patients infected with 2019-nCoV.

NCT04273646
Conditions
  1. 2019 Novel Coronavirus Pneumonia
  2. COVID-19
Interventions
  1. Biological: UC-MSCs
  2. Drug: Placebo
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of Pneumonia Improvement

Measure: Pneumonia severity index

Time: From Baseline (0W) to 12 week after treatment

Description: Evaluation of Pneumonia Improvement

Measure: Oxygenation index (PaO2/FiO2)

Time: From Baseline (0W) to 12 week after treatment

Secondary Outcomes

Description: Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.

Measure: Side effects in the UC-MSCs treatment group

Time: From Baseline (0W) to 96 week after treatment

Description: Marker for efficacy of treatment

Measure: 28-days survival

Time: Day 28

Description: Markers of organ function(Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.)

Measure: Sequential organ failure assessment

Time: Day 28

Description: Markers of Infection

Measure: C-reactive protein

Time: From Baseline (0W) to 12 week after treatment

Description: Markers of Infection

Measure: Procalcitonin

Time: From Baseline (0W) to 12 week after treatment

Description: Marker of Immunological function

Measure: Lymphocyte count

Time: From Baseline (0W) to 12 week after treatment

Description: Marker of Immunological function

Measure: CD3+, CD4+ and CD8+ T celll count

Time: From Baseline (0W) to 12 week after treatment

Description: Marker of Immunological function

Measure: CD4+/CD8+ratio

Time: From Baseline (0W) to 12 week after treatment
23 Evaluating the Efficacy and Safety of Bromhexine Hydrochloride Tablets Combined With Standard Treatment/ Standard Treatment in Patients With Suspected and Mild Novel Coronavirus Pneumonia (COVID-19)

Compare the efficacy and safety of Bromhexine Hydrochloride Tablets combined with standard treatment/ standard treatment in patients with suspected and mild, or common novel coronavirus pneumonia (COVID-19). Random, open, group sequential design.

NCT04273763
Conditions
  1. Novel Coronavirus Pneumonia
  2. 2019-nCoV
Interventions
  1. Drug: Bromhexine Hydrochloride Tablets
  2. Drug: Arbidol Hydrochloride Granules
  3. Drug: Recombinant Human Interferon α2b Spray
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Defined as random to fever, respiratory rate return to normal and cough remission over 48 hours.

Measure: Time to clinical recovery after treatment

Time: within 14 days from the start of medication

Description: Aggravation was defined as(one of them): respiratory distress, RR ≥ 30 times / min; SpO2 ≤ 93% in resting state; arterial partial pressure of oxygen (PaO2) /concentration of oxygen (FiO2) ≤ 300mmHg

Measure: Rate of aggravation

Time: within 14 days from the start of medication

Secondary Outcomes

Description: Clinical remission was defined as (one of them): sustained (more than 48 hours) alleviation of illness based on symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) all being absent and no evidence for progression.

Measure: Clinical remission rate

Time: within 14 days from the start of medication

Description: oxygenation index

Measure: Dynamic changes of oxygenation index

Time: within 14 days from the start of medication

Description: time of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery

Measure: Time to cure

Time: within 14 days from the start of medication

Description: proportion of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery among infected patients

Measure: rate to cure

Time: within 14 days from the start of medication

Description: defervescence is defined as below 37 Celcius degrees(ear temperature)

Measure: Time to defervescence

Time: within 14 days from the start of medication

Measure: Time to cough remission

Time: within 14 days from the start of medication

Measure: Time to dyspnea remission

Time: within 14 days from the start of medication

Measure: Days of supplemental oxygenation

Time: within 14 days from the start of medication

Measure: Rate of patients with requring supplemental oxygen

Time: within 14 days from the start of medication

Measure: Rate of patients with mechanical ventilation

Time: within 14 days from the start of medication

Measure: Time of negative COVID-19 nucleic acid results

Time: within 14 days from the start of medication

Measure: Rate of negative COVID-19 nucleic acid results

Time: within 14 days from the start of medication

Measure: Rate of ICU admission

Time: within 14 days from the start of medication

Measure: 28-day mortality

Time: From the first day of screening to the day of follow-up (28 days)
24 Single Center, Single Arm, Open Clinical Study to Access Safety and Initial Efficacy of Anti-CD147 Humanized Meplazumab for Injection to Treat With 2019-nCoV Pneumonia

To evaluate the safety and efficacy of humanized Meplazumab for Injection in patients infected by 2019-nCoA.

NCT04275245
Conditions
  1. 2019-nCoVs Infection Pneumonia
Interventions
  1. Drug: Meplazumab for Injection
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Virological clearance rate using Real-Time PCR in upper and/or lower respiratory tract samples at day 3, day 7 and day 14 respectively.

Measure: 2019 nCoV nucleic acid detection

Time: 14 days

Secondary Outcomes

Description: Time (days) from initiation of Meplazumab treatment until normalization of body temperature (≤37℃ axilla)

Measure: Recovery of body temperature

Time: 14 days

Description: Time (days) from initiation of Meplazumab treatment until normalization of resting respiratory rate (≤24/min)

Measure: Recovery of resting respiratory rate

Time: 14 days

Description: Time (days) from initiation of Meplazumab treatment until normalization of SPO2 (>94%)

Measure: Recovery of SPO2

Time: 14 days

Description: Rate of lung imaging recovery

Measure: Chest CT / chest film changes

Time: 28 days

Description: Rate of PaO2 / FiO2 recovery

Measure: PaO2 / FiO2

Time: 14 days

Description: Days to reach the isolation release standard

Measure: Time to reach the isolation release standard

Time: 28 days

Description: Rate of CRP, D-Dimer test recovery

Measure: Changes of inflammatory immune status

Time: 14 days
25 Retrospective Cohort to Evaluate the Effectiveness and Safety of Xiyanping Injection Combined With Conventional Treatment for New Coronavirus Infection Pneumonia (Common Type)

the investigators conduct a randomized, open-label trial to evaluate and compare the safety and efficacy of Xiyanping injection in patients with 2019-nCoV pneumonia.

NCT04275388
Conditions
  1. 2019 Novel Coronavirus Pneumonia
Interventions
  1. Drug: Xiyanping injection
  2. Drug: Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: From the beginning of study drug use to fever, respiratory rate, blood oxygen saturation to normal and cough relief, and maintained for at least 72 hours or more, calculated in hours

Measure: Clinical recovery time

Time: Up to Day 14

Secondary Outcomes

Description: From the beginning of research drug use to body temperature <37.3 ℃ (underarm) or mouth temperature ≤37.5 ° C, or anal or ear temperature ≤37.8 ° C, and maintained for 24h or more

Measure: Complete fever time

Time: Up to Day 14

Description: Cough score "day + night" from the beginning of study medication to cough ≤ 1 point, and maintained for 24 hours and above

Measure: Cough relief time

Time: Up to Day 14

Description: From the beginning of the study drug to two consecutive times (sampling interval of at least 1 day)

Measure: Virus negative time

Time: Up to Day 14

Description: Defined as the proportion of subjects exacerbated during treatment and meeting the diagnostic criteria for severe or critical neocoronavirus pneumonia

Measure: Incidence of severe or critical neocoronavirus pneumonia

Time: Up to Day 14
26 A Pilot Clinical Study on Aerosol Inhalation of the Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in the Treatment of Severe Patients With Novel Coronavirus Pneumonia

In December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).

NCT04276987
Conditions
  1. Coronavirus
Interventions
  1. Biological: MSCs-derived exosomes
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)

Measure: Adverse reaction (AE) and severe adverse reaction (SAE)

Time: Up to 28 days

Description: Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)

Measure: Time to clinical improvement (TTIC)

Time: Up to 28 days

Secondary Outcomes

Description: Number of patients weaning from mechanical ventilation within 28 days

Measure: Number of patients weaning from mechanical ventilation

Time: Up to 28 days

Description: Duration (days) of ICU monitoring within 28 days

Measure: Duration (days) of ICU monitoring

Time: Up to 28 days

Description: Duration (days) of vasoactive agents using within 28 days

Measure: Duration (days) of vasoactive agents usage

Time: Up to 28 days

Description: Duration (days) of mechanical ventilation supply among survivors

Measure: Duration (days) of mechanical ventilation supply

Time: Up to 28 days

Description: Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs

Measure: Number of patients with improved organ failure

Time: Up to 28 days

Description: Rate of mortality within 28 days

Measure: Rate of mortality

Time: Up to 28 days

Other Outcomes

Description: Records of daily sequential organ failure assessment (SOFA) score (From 0 to 24 points, higher scores mean a worse outcome)

Measure: Sequential organ failure assessment (SOFA) score

Time: Every day for 28 days

Description: Records of Blood routine test

Measure: Lymphocyte Count (10E9/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Measure: C-reactive protein (CRP) (mg/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Measure: Lactate dehydrogenase (U/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Coagulation function

Measure: D-dimer (mg/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Records of heart failure

Measure: pro-type B natriuretic peptide (pro-BNP) (pg/ml)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Record of serum cytokine

Measure: IL-1β (pg/ml)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Record of serum cytokine

Measure: IL-2R (ng/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Record of serum cytokine

Measure: IL-6 (ng/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Record of serum cytokine

Measure: IL-8 (ng/L)

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Computed tomography or X-ray

Measure: Chest imaging

Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

Description: Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens

Measure: Time to SARS-CoV-2 RT-PCR negativity

Time: Up to 28 days
27 Clinical Investigation of Natural Killer Cells Treatment in Pneumonia Patients Infected With 2019 Novel Coronavirus

Since december 2019, acute respiratory disease due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. There is no confirmed antivirus therapy for 2019-nCoV infection. Natural killer (NK) cells are innate lymphocytes that may serve as useful effectors against danger infection. The purpose of this clinical investigation is to evaluate the safety and efficiency of NK Cells in combination with standard therapy for pneumonia patients infected with 2019-nCoV.

NCT04280224
Conditions
  1. Novel Coronavirus Pneumonia
Interventions
  1. Biological: NK Cells
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of pneumonia improvement

Measure: Improvement of clinical symptoms including duration of fever

Time: Measured from day 0 through day 28

Description: Evaluation of pneumonia improvement

Measure: Improvement of clinical symptoms including respiratory frequency

Time: Measured from day 0 through day 28

Description: Safety evaluation

Measure: Number of participants with treatment-related adverse events evaluated with CTCAE,version 4.0

Time: Measured from day 0 through day 28

Secondary Outcomes

Description: Marker for 2019-nCoV

Measure: Time of virus nucleic acid test negative

Time: Measured from day 0 through day 28

Description: Marker of immunological function

Measure: CD4+ and CD8+ T cell count

Time: Measured from day 0 through day 28

Description: Marker for efficacy of treatment

Measure: Rate of mortality within 28-days

Time: Day 28

Description: Recovery of lung injury

Measure: Size of lesion area by thoracic imaging

Time: Measured from day 0 through day 28
28 Identification of a New Screening Strategy for 2019 Novel Coronavirus Infection

Since Dec 2019, over 70000 novel coronavirus infection pneumonia (NCIP) patients were confirmed. 2019 novel coronavirus (2019 nCoV) is a RNA virus, which spread mainly from person-to-person contact. Most of the symptoms are non-specific, including fever, fatigue, dry cough. Sever NCIP patients may have shortness of breath and dyspnea, and progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The mortality is reported to be around 2.3%. Thus, early detection and early treatment is very important to the improvement of NCIP patients' prognosis. At present, NCIP RNA detection of pharyngeal swab specimen by RT-PCR is recommended. However, due to the universal susceptibility to 2019 nCoV in general population and limited number of NCIP RNA detection kits available, to identify an efficient screening strategy is urgently needed. This study aim to develop and validate the diagnostic accuracy and screening efficiency of a new NCIP screening strategy, which can benefit the disease prevention and control.

NCT04281693
Conditions
  1. Novel Coronavirus Infection Pneumonia
Interventions
  1. Diagnostic Test: Standard screening strategy
  2. Diagnostic Test: New screening strategy
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The screening accuracy of the two screening strategies were calculated and compared.

Measure: Screening accuracy

Time: 1 month

Secondary Outcomes

Description: The costs of the two screening strategies were recorded. Cost-effectiveness analysis were performed and compared.

Measure: Cost-effectiveness analysis

Time: 1 month
29 CT Scores Predict Mortality in 2019-nCoV Pneumonia

While 2019-nCoV nucleic acid swab tests has high false positives rate, How to diagnose 2019-nCoV pneumonia and predict prognosis by CT is very important.In this retrospective single-center study, we consecutively included suspected 2019-nCoV pneumonia critical cases in the intensive care unit of Wuhan third hospital from January 31, 2020 to February 16, 2020. The cases were confirmed by real-time RT-PCR, and all patients were evaluated with CT, cutoff values were obtained according to the Yoden index, and were divided into high CT score group and low CT score group. Epidemiological, demographic, clinical, and laboratory data were collected.

NCT04284046
Conditions
  1. CT Scores Predict Mortality in 2019-nCoV Pneumonia
Interventions
  1. Other: CT score
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: 7-day mortality

Time: 7-day
30 A Clinical Study to Investigate the Effect of T89 on Improving Oxygen Saturation and Clinical Symptoms in Patients With Coronavirus Disease 2019 (COVID-19)

This is an open-label, randomized, blank-controlled treatment clinical study. The objective of this study is to investigate the effect of T89 on improving oxygen saturation and clinical symptoms in patients with Coronavirus Disease 2019 (COVID-19). In this study, estimated total of 120-240 male and female patients who have been diagnosed with non-critical type of coronavirus pneumonia (COVID-19) will be enrolled and randomly assigned to one of two study groups, the T89 treatment group and the blank control group, to T89 or nothing on the base of a recommended standard treatment for up to 14 days . The primary efficacy parameters include the time to oxygen saturation recovery to normal level (≥97%), the proportion of patients with normal level of oxygen saturation after treatment, and the total duration of oxygen inhalation, oxygen flow change by time, oxygen concentration change by time during treatment.

NCT04285190
Conditions
  1. Coronavirus Disease 2019
  2. Novel Coronavirus Pneumonia
Interventions
  1. Drug: T89
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: From screening to the end of treatment, for all patients randomized, oxygen saturation will be assessed for 3 times daily, the time to oxygen saturation recovery to normal level (≥97%) will be calculated finally based on that record and compared between two groups.

Measure: The time to oxygen saturation recovery to normal level (≥97%)

Time: Day -1 to 10

Description: The proportion of patients with normal level of oxygen saturation(≥97%) after treatment will be calculated finally based on that record and compared between two groups.

Measure: The proportion of patients with normal level of oxygen saturation(≥97%)

Time: Day -1 to 10

Secondary Outcomes

Description: From screening to the end of treatment, for all patients randomized, the symptoms will be assessed 2 times daily, and the time to achievement of remission for each symptom will be calculated finally based on the record and compared between two groups.

Measure: The degree of remission of symptoms of patients, including: fatigue, nausea, vomiting, chest tightness, shortness of breath, etc.

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal will be calculated finally based on the record and compared between two groups.

Measure: The time to the myocardial enzyme spectrum recovery to normal after treatment

Time: Day -1, 3, 7 and 10

Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal myocardial enzyme spectrum after treatment will be calculated finally based on the record and compared between two groups.

Measure: The proportion of the patients with normal myocardial enzyme spectrum after treatment

Time: Day -1, 3, 7 and 10

Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal level will be calculated finally based on the record and compared between two groups.

Measure: The time to the electrocardiogram recovery to normal level after treatment

Time: Day -1, 3, 7 and 10

Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal electrocardiogram will be calculated finally based on the record and compared between two groups.

Measure: The proportion of the patients with normal electrocardiogram after treatment

Time: Day -1, 3, 7 and 10

Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the hemodynamics recovery to normal will be calculated finally based on the record and compared between two groups.

Measure: The time to the hemodynamics recovery to normal after treatment

Time: Day -1 and 10

Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal hemodynamics will be calculated finally based on the record and compared between two groups.

Measure: The proportion of the patients with normal hemodynamics after treatment

Time: Day -1 and 10

Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The time to exacerbation or remission of the disease will be calculated finally based on the record and compared between two groups.

Measure: The time to exacerbation or remission of the disease after treatment;

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The proportion of patients whose disease get aggravated or alleviated will be calculated finally based on the record and compared between two groups.

Measure: The proportion of the patients with exacerbation or remission of disease after treatment

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, the need for additional treatment will be recorded and compared between two groups.

Measure: The proportion of patients who need other treatment (e.g. heparin, anticoagulants) due to microcirculation disorders

Time: Day -1 to 10

Description: For all patients, the mortality will be recorded in each group and the rate will be compared between two groups.

Measure: The all-cause mortality rate

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, the proportion of patients with acidosis will be compared between two groups based on the hemodynamics results.

Measure: The proportion of patients with acidosis

Time: Day -1 and 10

Description: For all patients, the duration of hospitalization will be recorded in each group and compared between two groups.

Measure: The total duration of the patients in-hospital

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, the total duration of oxygen inhalation during oxygen treatment will be assessed and compared, if applicable, between two groups.

Measure: The total duration of oxygen inhalation during treatment

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, the oxygen flow rate during oxygen treatment will be assessed and compared, if applicable, between two groups.

Measure: The oxygen flow rate during treatment

Time: Day -1 to 10

Description: From screening to the end of treatment, for all patients randomized, the oxygen concentration during oxygen treatment will be assessed and compared, if applicable, between two groups.

Measure: The oxygen concentration during treatment

Time: Day -1 to 10
31 Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID19 Infection: a Randomized Clinical Trial

The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on COVID-19 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.

NCT04290858
Conditions
  1. Coronavirus Infections
  2. Pneumonia, Viral
  3. Dyspnea
Interventions
  1. Drug: Nitric Oxide
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Dyspnea
HPO:Dyspnea Pneumonia Respiratory distress

Primary Outcomes

Description: The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.

Measure: Reduction in the incidence of intubation and mechanical ventilation

Time: 28 days

Secondary Outcomes

Description: Mortality from all causes

Measure: Mortality

Time: 28 days

Description: Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or a nasopahryngeal swab

Measure: Negative conversion of COVID-19 RT-PCR from upper respiratory tract

Time: 7 days

Description: Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air) and alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent).

Measure: Time to clinical recovery

Time: 28 days
32 Clinical Progressive Characteristics and Treatment Effects of 2019-novel Coronavirus(2019-nCoV)

Objects: The purpose of this study was to observe the characteristics of morbidity, disease progression and therapeutic effects of 2019-novel coronavirus pneumonia patients with different clinical types. Method: A single center, retrospective and observational study was used to collect COVID-19 patients admitted to Wuhan Infectious Diseases Hospital (Wuhan JinYinTan Hospital) from January 2020 to March 2020. The general information, first clinical symptoms, hospitalization days, laboratory examination, CT examination, antiviral drugs, immune enhancers, traditional Chinese medicine treatment and other clinical intervention measures were recorded, and the nutritional status and prognosis of the patients were recorded. confirm COVID-19 's disease progression, clinical characteristics, disease severity and treatment effects. To compare the characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Outcomes: The characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Conclusion: The characteristics of disease progression, clinical features and therapeutic effect of different types of COVID-19.

NCT04292327
Conditions
  1. Pneumonia Caused by Human Coronavirus
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The mortality of COVID-19 in 28 days

Measure: Mortality

Time: 28 day

Description: The time interval of COVID-19 form nucleic acid confirmed to the nucleic acid detection turn into negative.

Measure: The time interval of Nucleic acid detection become negative

Time: 28 day
33 Human Umbilical Cord Mesenchymal Stem Cells Treatment for Pneumonia Patients Infected by 2019 Novel Coronavirus

The 2019 novel coronavirus pneumonia outbroken in Wuhan, China, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, there is no effective treatment in clinical practice. The present clinical trial is to explore the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for novel coronavirus pneumonia patients.

NCT04293692
Conditions
  1. COVID-19
Interventions
  1. Biological: UC-MSCs
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of Pneumonia change

Measure: Size of lesion area by chest imaging

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Evaluation of Pneumonia change

Measure: Blood oxygen saturation

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Secondary Outcomes

Description: Marker for efficacy of treatment

Measure: Rate of mortality within 28-days

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: 0-4 score, the higher the score is, the poor of the prognosis will be.

Measure: Sequential organ failure assessment

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Number of participants with treatment-related adverse events

Measure: Side effects in the UC-MSCs treatment group

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Markers of the heart function

Measure: Electrocardiogram, the changes of ST-T interval mostly

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Markers of infection

Measure: Concentration of C-reactive protein C-reactive protein, immunoglobulin

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Marker of Immunology and inflammation

Measure: CD4+ and CD8+ T cells count

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Marker of Immunology and inflammation

Measure: Concentration of the blood cytokine (IL-1β, IL-6, IL-8,IL-10,TNF-α)

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Markers of the heart function

Measure: Concentration of the myocardial enzymes

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
34 Multicenter Clinical Study on the Efficacy and Safety of Xiyanping Injection in the Treatment of New Coronavirus Infection Pneumonia (General and Severe)

In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Xiyanping injection has anti-inflammatory and immune regulation effects. This study is a Randomized, Parallel Controlled Clinical Study to treat patients with COVID-19 infection.

NCT04295551
Conditions
  1. COVID-19
Interventions
  1. Drug: Lopinavir / ritonavir tablets combined with Xiyanping injection
  2. Drug: Lopinavir/ritonavir treatment
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The time from study drug use to complete fever reduction and cough recovery is measured in hours.

Measure: Clinical recovery time

Time: Up to Day 28
35 Analysis of Safety Related Factors of Endotracheal Intubation in Patients With Severe Covid-19 Pneumonia

To analyze the intubation with severe covid-19 pneumonia, the infection rate of anesthesiologist after intubation, and summarizes the experience of how to avoid the infection of anesthesiologist and ensure the safety of patients with severe covid-19 pneumonia.

NCT04298814
Conditions
  1. COVID-19
  2. Endotracheal Intubation
Interventions
  1. Other: severe covid-19 pneumonia with ET
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The data of Success rate of intubation with severe COVID-19 pneumonia patients

Measure: Success rate of intubation

Time: the time span between 1hour before intubation and 24h after intubation

Description: Infection rate of Anesthesiologist who performed the endotracheal intubation for severe COVID-19 pneumonia patients

Measure: Infection rate of Anesthesiologist

Time: the time span between 1hour before intubation and 14days after intubation

Secondary Outcomes

Description: Extubation time of intubated severe COVID-19 pneumonia patients

Measure: Extubation time

Time: the time span between 1hour before intubation and 30days after intubation
36 Clinical Application of Stem Cell Educator Therapy for the Treatment of Viral Inflammation Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Currently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.

NCT04299152
Conditions
  1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Combination Product: Stem Cell Educator-Treated Mononuclear Cells Apheresis
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Inflammation
HPO:Pneumonia

Primary Outcomes

Description: The feasibility will be evaluated by the number of Covid-19 patients who were unable to complete SCE Therapy.

Measure: Determine the number of Covid-19 patients who were unable to complete SCE Therapy

Time: 4 weeks

Secondary Outcomes

Description: Measurements of immune markers' changes will be preformed by flow cytometry such as activated T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.

Measure: Examine the percentage of activated T cells after SCE therapy by flow cytometry

Time: 4 weeks

Description: Measurements of immune marker's changes will be preformed by flow cytometry such as the percentage of Th17 cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.

Measure: Assess the percentage of Th17 cells after SCE therapy by flow cytometry

Time: 4 weeks

Description: Patients will be monitored for their chest imaging every 3 - 5 days for 4 weeks after receiving SCE therapy.

Measure: Chest imaging changes by computed tomography (CT) scan of the chest

Time: 4 weeks

Description: To determine the viral load by real time RT-PCR, samples of blood, sputum, nose / throat swab will be collected from patients during the follow-up studies after receiving SCE therapy.

Measure: Quantification of the SARS-CoV-2 viral load by real time RT-PCR

Time: 4 weeks
37 Clinical Study of Novel Coronavirus Induced Severe Pneumonia Treated by Dental Pulp Mesenchymal Stem Cells

Evaluation of novel coronavirus induced severe pneumonia by dental pulp mesenchymal stem cells

NCT04302519
Conditions
  1. COVID-19
Interventions
  1. Biological: Dental pulp mesenchymal stem cells
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Kaplan-meier method was used to calculate the median glassy shadow time in all subjects

Measure: Disppear time of ground-glass shadow in the lungs

Time: 14 days

Secondary Outcomes

Description: Kaplan-meier method was used to calculate the median lung shadow absorption of all subjects on 7, 14, 28, and 360 days

Measure: Absorption of Lung shadow absorption by CT Scan-Chest

Time: 7, 14, 28 and 360 days

Description: T test was used to compare the blood oxygen values of each subject at day 3, 7 and 14

Measure: Changes of blood oxygen

Time: 3, 7 and 14 days
38 Accurate Classification System for Patients With COVID-19 Based on Prognostic Nomogram

The COVID-19 has a clustering morbidity trend and older people with chronic diseases are more likely to die, such as chronic renal insufficiency and chronic cardiovascular disease. We set up a COVID-19 pneumonia grading scale. The COVID-19 score system was validated to predict the clinical outcome of a patient.

NCT04302688
Conditions
  1. Pneumonitis
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: survival status as of February 24, 2020

Measure: survival status

Time: 10 December 2019 to 10 February 2020
39 The Efficacy and Safety of Bevacizumab in Severe or Critical Patients With COVID-19--a Multicenter Randomized Controlled Clinical Trial

The novel coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019, which causes epidemic worldwide. Novel coronavirus disease (COVID-19) causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the severe and critically severe patients. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patients died from COVID-19 reported that, pulmonary mucus exudation was severe, more obvious than SARS infection. Pulmonary CT scanning and pathological findings also suggest that pulmonary edema caused by inflammatory exudation is a distinguished feature of COVID-19. However, specific pharmacotherapy is lacking.Vascular endothelial growth factor (VEGF) is known as the most potent inducing factors to increase vascular permeability. Bevacizumab is an anti VEGF recombinant humanized monoclonal antibody, which has been used in anti-tumor treatment for 16 years. Evidence suggest that Bevacizumab is a promising drug for severe and critical COVID-19 patients.

NCT04305106
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Bevacizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The time from randomization to an improvement of two points on a seven-category ordinal scale or live discharge from the hospital

Measure: The time from randomization to clinical improvement

Time: No more than 28 days
40 An Adaptive, Randomized, Double-blind, Parallel-controlled Clinical Trial of Yinhu Qingwen Granula for the Treatment of Severe CoVID-19

In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia caused by CoVID-19, and the number of cases of infection with CoVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally.Given no specific antiviral therapy for CoVID-19 infection and the availability of Yinhu Qingwen Granula as a potential antiviral Chinese medicine based on vivo antiviral studies in CoVID-19, this adaptive, randomized,double-blind,controlled trial will evaluate the efficacy and safety of Yinhu Qingwen Granula in patients hospitalized with severe CoVID-19.

NCT04310865
Conditions
  1. COVID-19
  2. Severe Pneumonia
  3. Chinese Medicine
Interventions
  1. Drug: Yinhu Qingwen Granula
  2. Drug: Yin Hu Qing Wen Granula(low does)
  3. Other: standard medical treatment
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: changes in the ratio of PaO2 to FiO2 from baseline

Time: Day 10

Secondary Outcomes

Measure: PaO2

Time: up to 30 days

Measure: blood oxygen saturation (SpO2)

Time: up to 30 days

Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

Measure: clinical status rating on the 7-point ordinal scale

Time: up to 30 days

Description: TTCI is defined as the time (in days) from initiation of study treatment (Yinhu Qingwen Granula or its low-dose granula) until a decline of two categories from status at randomisation on the 7-point ordinal scale of clinical status which ranges from 0 (death) to 6 (Not hospitalized, no limitations on activities).

Measure: Time to Clinical Improvement (TTCI)

Time: up to 30 days

Measure: Duration (hours) of non-invasive mechanical ventilation or high-flow nasal catheter oxygen inhalation use

Time: up to 30 days

Measure: Duration (hours) of invasive mechanical ventilation use

Time: up to 30 days

Measure: Duration (hours) of extracorporeal membrane oxygenation (ECMO) use

Time: up to 30 days

Measure: Duration (days) of Oxygen use

Time: up to 30 days

Measure: The proportion of the patients reporting 2019-nCoV RT-PCR negativity at Day 10 after treatment

Time: Day 10

Measure: The counts/percentage of Lymphocyte

Time: up to 30 days

Measure: Time to hospital discharge with clinical recovery from the randomisation

Time: up to 30 days

Description: Critical status is defined as: 1) respiratory failure with the need of invasive mechanical ventilation; or 2) shock; or 3) other system organ failure with ICU admission.

Measure: The incidence of critical status conversion in 30 days

Time: up to 30 days

Measure: All-cause mortality within 30 days

Time: up to 30 days

Measure: Frequency of severe adverse drug events

Time: up to 30 days
41 The Benefits of Artificial Intelligence Algorithms (CNNs) for Discriminating Between COVID-19 and Influenza Pneumonitis in an Emergency Department Using Chest X-Ray Examinations

This project aims to use artificial intelligence (image discrimination) algorithms, specifically convolutional neural networks (CNNs) for scanning chest radiographs in the emergency department (triage) in patients with suspected respiratory symptoms (fever, cough, myalgia) of coronavirus infection COVID 19. The objective is to create and validate a software solution that discriminates on the basis of the chest x-ray between Covid-19 pneumonitis and influenza

NCT04313946
Conditions
  1. COVID-19
  2. Pneumonia, Viral
  3. Influenza With Pneumonia
  4. Flu Symptom
  5. Flu Like Illness
  6. Pneumonia, Interstitial
  7. Pneumonia, Ventilator-Associated
  8. Pneumonia Atypical
Interventions
  1. Diagnostic Test: Scanning Chest X-rays and performing AI algorithms on images
MeSH:Pneumonia, Ventilator-Associated Influenza, Human Pneumonia, Viral Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Number of participants with pneumonitis on Chest X-Ray and COVID 19 positive

Measure: COVID-19 positive X-Rays

Time: 6 months

Description: Number of participants with pneumonitis on Chest X-Ray and COVID 19 negative

Measure: COVID-19 negative X-Rays

Time: 6 months
42 Tocilizumab (RoActemra) as Early Treatment of Patients Affected by SARS-CoV2 (COVID-19) Infection With Severe Multifocal Interstitial Pneumonia

In a Phase 2 Simon's Optimal Two-Stages Design intravenous tocilizumab will be administered as single 8mg/Kg dose in patients affected by severe multifocal interstitial pneumonia correlated to SARS-CoV2 infection. Aim of the study is to test the hypothesis that an anti-IL6 treatment can be effective in calming the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing naso-tracheal intubation and/or death.

NCT04315480
Conditions
  1. SARS Pneumonia
Interventions
  1. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: rate of patients with no need in increase of FiO2 to maintain stable SO2 and no need of intubation

Measure: arrest in deterioration of pulmonary function

Time: 7days

Description: rate of patients with change of oxygen saturation >3 percentage points or >10% or decrease in FiO2 need or reduction in pulmonary consolidations >30% at HR CT-scan

Measure: improving in pulmonary function

Time: 7 days

Secondary Outcomes

Description: rate of patients needed of intubation

Measure: need of oro-tracheal intubation

Time: +7 days

Description: rate of patients dead

Measure: death

Time: 14days
43 Exploratory Clinical Study to Assess the Efficacy of NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

This is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.

NCT04315987
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Biological: NestaCell®
  2. Biological: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Ordinal scale (WHO ordinal scale that measures illness severity over time)

Measure: Change in Clinical Condition

Time: 10 days

Secondary Outcomes

Description: Evaluation of Pneumonia change

Measure: Rate of mortality within 10-days

Time: 10 days

Description: Evaluation of Pneumonia change

Measure: Change of Clinical symptoms - respiratory rate

Time: 10 days

Description: oxygen saturation

Measure: Hypoxia

Time: 10 days

Description: oxygen saturation

Measure: PaO2 / FiO2 ratio

Time: 10 days

Description: Marker of Immunological function

Measure: CD4+ and CD8+ T cell count

Time: Days 1, 2, 4, 6 and 8.

Description: PaO2 / FiO2 ratio

Measure: Changes of blood oxygen

Time: 10 days

Description: Number of participants with treatment-related adverse events

Measure: Side effects in the treatment group

Time: 10 days

Description: Complete blood count, ALT, AST, GGT, CK, CKmB and creatinine

Measure: Complete blood count, cardiac, hepatic and renal profiles;

Time: Days 1, 2, 4, 6 and 8.
44 Predictors of Respiratory Failure Requiring ICU Admission Among Hospitalized Patients With SARS-Cov-2 Infection

The emergence of SARS-CoV-2 is currently engaging and consuming most of resources of efficient healthcare systems in Europe, and several hospitals are currently experiencing a shortage of ICU beds for critically-ill patients with SARS-CoV-2 pneumonia. A risk stratification based on clinical, radiological and laboratory parameters seems necessary in order to better identify those patients who may need ICU admission and/or those who may benefit from a prompt antiviral therapy

NCT04316949
Conditions
  1. SARS-CoV-2 Pneumonia
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: Composite of ICU admission or SpO2<92% with 100% FiO2 of oxygen treatment (reservoir mask or CPAP or NIV), respiratory rate >30 bpm, respiratory distress

Measure: Respiratory failure

Time: 14 days

Secondary Outcomes

Description: Incidence of bacterial superinfection among ventilated patients with SARS-CoV-2 pneumonia

Measure: Occurence of bacterial superinfection

Time: 14 days
45 Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia

This study project includes a single-arm phase 2 study and a parallel cohort study, enrolling patients with COVID-19 pneumonia.

NCT04317092
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Tocilizumab Injection
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: 2-week lethality is defined as the ratio of the number of subjects dead within 14 days from study start out of phase 2 patients with baseline information.

Measure: Lethality rate two weeks after registration

Time: up to 15 days

Description: 1-month lethality is defined as the ratio of the number of subjects dead within 30 days from study start out of phase 2 patients with baseline information.

Measure: Lethality rate one month after registration

Time: up to 1 month

Secondary Outcomes

Description: IL-6 levels will be assessed using commercial ELISA method.

Measure: Interleukin-6 level

Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

Description: Lymphocyte count assessed by routinely used determination of blood count

Measure: Lymphocyte count

Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

Description: CRP is assessed by routinely used determination of CRP

Measure: CRP (C-reactive protein) level

Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

Description: calculated from arterial blood gas analyses (values from 300 to 100)

Measure: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)

Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

Description: It evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24.

Measure: Change of the SOFA (Sequential Organ Failure Assessment)

Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

Description: graded according to CTCAE citeria (v5.0)

Measure: Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0

Time: during treatment and up to 30 days after the last treatment dose

Description: Thoracic CT scan or Chest XR

Measure: Radiological response

Time: at baseline (optional), after seven days and if clinically indicated (up to 1 month)

Description: Days of hospitalization

Measure: Duration of hospitalization

Time: from baseline up to patient's discharge (up to 1 month)

Description: time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation

Measure: Remission of respiratory symptoms

Time: up to 1 month

Description: time to definitive extubation calculated from intubation (any time occurred) to extubation in days

Measure: Remission of respiratory symptoms

Time: up to 1 month

Description: time to independence from non-invasive mechanical ventilation calculated in days

Measure: Remission of respiratory symptoms

Time: up to 1 month

Description: time to independence from oxygen therapy in days

Measure: Remission of respiratory symptoms

Time: up to 1 month
46 Automated Oxygen Titration - Monitoring and Weaning in Patients With Infectious Pneumonia Requiring Oxygen - Impact on the Number of Interventions for Healthcare Workers. An Innovative Device to Manage Patients With COVID-19 Pneumonia COVID Study (Closed-Loop Oxygen to Verify That Healthcare Workers Interventions Decreaseduring Pneumonia)

There is a high risk of transmission of COVID-19 to healthcare workers. In a recent cohort, 29% of the patients hospitalized were healthcare workers. Among the WHO's primary strategic objectives for the response to COVID-19, the first was to limit human-to-human transmission, including reducing secondary infections among close contacts and health care workers. Automated oxygen titration, weaning and monitoring (FreeO2 device) may be a solution to reduce the number of interventions of healthcare workers related to oxygen therapy, to reduce complications related to oxygen and to improve monitoring.

NCT04320056
Conditions
  1. Coronavirus
  2. Pneumonia
  3. Oxygen Toxicity
Interventions
  1. Other: Standard administration of oxygen flow
  2. Device: Automated oxygen administration - FreeO2
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The number of interventions required by healthcare workers to manage oxygen therapy (titration, weaning and monitoring) during 4 hours

Measure: The number of interventions

Time: Hour0 to Hour4

Description: The number of interventions required by healthcare workers to manage oxygen therapy (titration, weaning and monitoring) during 4 hours

Measure: Duration of interventions

Time: Hour0 to Hour24

Secondary Outcomes

Description: The Mean oxygen flow during study duration to evaluate oxygen consumption

Measure: Mean oxygen flow

Time: Hour0 to Hour24 (1 day)

Description: Time within SpO2 between 90 and 94%

Measure: Time within theSpO2 target

Time: Hour0 to Hour24 (1 day)

Description: Time within SpO2 < 88%

Measure: Time with hypoxemia

Time: Hour0 to Hour24 (1 day)

Description: Time within SpO2 > 96%

Measure: Time with hyperoxemia

Time: Hour0 to Hour24 (1 day)

Description: Rate of ICU admission

Measure: Rate of ICU admission

Time: Hour0 to Hour24 (1 day)

Description: Rate of needed non invasive respiratory support Non invasive ventilation or High Flow Nasal Therapy

Measure: Rate of needed non invasive respiratory support

Time: Hour0 to Hour24 (1 day)

Description: Rate of intubation

Measure: Rate of intubation

Time: Hour0 to Hour24 (1 day)

Description: Evaluation of NEWS 2 score evolution (National Early Warning score) correlate to patient evolution. The NEWS2 score will be calculate but no intervention will be made based on this score. Patient evolution will be compare at NEWS 2 interpretation. Interpretation A low score (NEWS 1-4) should prompt assessment by a competent registered nurse who should decide if a change to frequency of clinical monitoring or an escalation of clinical care is required. A medium score (ie NEWS of 5-6 or a RED score) should consider whether escalation of care to a team with critical-care skills is required (ie critical care outreach team). A high score (NEWS ≥7) should prompt emergency assessment by a clinical team/critical care outreach team with critical-care competencies and usually transfer of the patient to a higher dependency care area.

Measure: NEWS 2 score evolution

Time: Hour0 to Hour24 (1 day)

Description: Evaluation of EWSO2 score(Early Warning ScoreO2) evolution correlate to patient evolution The EWSO2 score will be calculate but no intervention will be made based on this score. Patient evolution will be compare at EWSO2 interpretation. Interpretation Favorable clinical outcome in patients with a score <5.3 A patient with a score >18.6 will experience a poor outcome.

Measure: EWSO2 score evolution

Time: Hour0 to Hour24 (1 day)

Description: Cost effectiveness ratio (cost per SpO2 unit)

Measure: Cost-effectiveness

Time: From date of randomization until the date of hospital discharge

Description: Duration of the hospital length of stay

Measure: length of stay

Time: up to 90 days. Hospital stay - hospital admission through hospital discharge or until death if occured
47 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.

NCT04320615
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Tocilizumab (TCZ)
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Clinical Status Assessed Using a 7-Category Ordinal Scale

Time: Day 28

Secondary Outcomes

Measure: Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of Time: Up to 60 days

Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

Time: Up to 60 days

Measure: Incidence of Mechanical Ventilation

Time: Up to 60 days

Measure: Ventilator-Free Days to Day 28

Time: Up to Day 28

Measure: Incidence of Intensive Care Unit (ICU) Stay

Time: Up to 60 days

Measure: Duration of ICU Stay

Time: Up to 60 days

Measure: Time to Clinical Failure

Time: From first dose to time of death, mechanical ventilation, ICU admission, or study withdrawal (whichever occurs first, for up to 60 days). If already in ICU on ventilation, failure = a one-category worsening on the ordinal scale, withdrawal, or death

Measure: Mortality Rate

Time: Days 7, 14, 21, 28, and 60

Measure: Time to Hospital Discharge

Time: Up to 60 days

Measure: Time to Recovery

Time: Up to 60 days

Measure: Duration of Time on Supplemental Oxygen

Time: Up to 60 days

Measure: Percentage of Participants with Adverse Events

Time: Up to 60 days

Measure: COVID-19 (SARS-CoV-2) Viral Load Over Time

Time: Up to 60 days

Measure: Time to Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Virus Negativity

Time: Up to 60 days

Measure: Proportion of Participants with Post-Treatment Infection

Time: Up to 60 days

Measure: Serum Concentration of IL-6

Time: Up to 60 days

Measure: Serum Concentration of sIL-6R

Time: Up to 60 days

Measure: Serum Concentration of Ferritin

Time: Up to 60 days

Measure: Serum Concentration of C-Reactive Protein (CRP)

Time: Up to 60 days

Measure: Serum Concentration of TCZ

Time: Up to 60 days
48 Evaluation of the Safety and Clinical Efficacy of Hydroxychloroquine Associated With Azithromycin in Patients With Pneumonia Caused by Infection by the SARS-CoV2 Virus - Coalition COVID-19 Brasil II - SEVERE - Patients

The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.

NCT04321278
Conditions
  1. Coronavirus Infections
  2. Pneumonia, Viral
Interventions
  1. Drug: Hydroxychloroquine + azithromycin
  2. Drug: Hydroxychloroquine
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

Measure: Evaluation of the clinical status

Time: 15 days after randomization

Secondary Outcomes

Description: All-cause mortality rates at 29 days after randomization

Measure: All-cause mortality

Time: 29 days after randomization

Description: Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

Measure: Evaluation of the clinical status

Time: 7 and 29 days after randomization

Description: Number of days free from mechanical ventilation at 29 days after randomization

Measure: Number of days free from mechanical ventilation

Time: 29 days after randomization

Description: Number of days that the patient was on mechanical ventilation after randomization

Measure: Duration of mechanical ventilation

Time: 29 days after randomization

Description: Length of hospital stay on survivors

Measure: Duration of hospitalization

Time: 29 days after randomization

Description: Presence of other secondary infections

Measure: Other secondary infections

Time: 29 days after randomization

Description: Time from treatment start to death

Measure: Time from treatment start to death

Time: 29 days after randomization

Description: Morbimortality, daily life activities, mental health, and quality of life

Measure: Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life

Time: 3, 6, 9 and 12 months

Description: Leucocyte transcriptome

Measure: Assess whether the tested therapies may be affected by leucocyte phenotype

Time: Baseline

Other Outcomes

Description: Occurrence of QT interval prolongation

Measure: QT interval prolongation

Time: 29 days after randomization

Description: Occurrence of gastrointestinal intolerance

Measure: Gastrointestinal intolerance

Time: 29 days after randomization

Description: Occurrence of laboratory hematimetric parameters, creatinine and bilirubin

Measure: Laboratory abnormalities

Time: 29 days after randomization

Description: Occurrence of adverse events related to the use of the investigational products

Measure: Adverse events

Time: 29 days after randomization
49 Proposal for International Standardization of the Use of Lung Ultrasound for COVID-19 Patients; a Simple, Quantitative, Reproducible Method

Growing evidences are showing the usefulness of lung ultrasound in patients with COVID-19. Sars-CoV-2 has now spread in almost every country in the world. In this study, the investigators share their experience and propose a standardized approach in order to optimize the use of lung ultrasound in covid-19 patients. The investigators focus on equipment, procedure, classification and data-sharing.

NCT04322487
Conditions
  1. Coronavirus
  2. Epidemic Disease
  3. Pneumonia, Viral
Interventions
  1. Diagnostic Test: Lung ultrasound
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Scoring procedures Score 0: The pleura line is continuous, regular. Horizontal artifacts (A-line) are present. These artifacts are generally referred as A-lines. Score 1: The pleura line is indented. Below the indent, vertical areas of white are visible. Score 2: The pleura line is broken. Below the breaking point, small to large consolidated areas (darker areas) appear with associated areas of white below the consolidated area (white lung). Score 3: The scanned area shows dense and largely extended white lung with or without larger consolidations At the end of the procedure, the clinician will write for each area the highest score obtained.

Measure: Lung ultrasound grading system for COVID-19 pneumonia

Time: At enrollment.
50 Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia

Cytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with SARS or MERS . The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and increased NLR in infected patients are correlated with the severity of the disease and adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19 pathogenesis. Importantly, previous studies showed that viroporin E, a component of SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome activation . The mechanisms are unclear. Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome, thereby reducing the release of IL-1b and an array of other interleukins, including IL-6, that are formed in response to danger signals. Recently, colchicine has been successfully used in two cases of life-threatening post-transplant capillary leak syndrome. These patients had required mechanically ventilation for weeks and hemodialysis, before receiving colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].

NCT04322565
Conditions
  1. Coronavirus Infections
  2. Pneumonia, Viral
Interventions
  1. Drug: Colchicine
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time to clinical improvement: defined as time from randomization to an improvement of two points from the status at randomization on a seven-category ordinary scale

Measure: Clinical improvement

Time: Day 28

Description: Live discharge from the hospital (whatever comes first)

Measure: Hospital discharge

Time: Day 28

Secondary Outcomes

Description: Number of death patients

Measure: Death

Time: Day 28

Description: 7-category ordinal scale

Measure: Clinical status

Time: Day 7, Day 14

Description: Number of patients with mechanical ventilhation

Measure: Mechanical ventilhation

Time: Day 28

Description: Days of hospitalization

Measure: Hospitalization

Time: Day 28

Description: Days to death from treatment initiation

Measure: Time from treatment initiation to death

Time: Day 28

Description: negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart

Measure: Time to Negativization COVID 19

Time: Day 21

Description: Time to remission of fever in patients with T>37.5°C at enrollment

Measure: Fever

Time: Day 1,4,7,14,21,28
51 Use of Ascorbic Acid in Patients With COVID 19

Different studies showed that ascorbic acid (vitaminC) positively affects the development and maturation of T-lymphocytes, in particular NK (natural Killer) cells involved in the immune response to viral agents. It also contributes to the inhibition of ROS production and to the remodulation of the cytokine network typical of systemic inflammatory syndrome. Recent studies have also demonstrated the effectiveness of vitamin C administration in terms of reducing mortality, in patients with sepsis hospitalized in intensive care wards. Given this background, in the light of the current COVID-19 emergency, since the investigators cannot carry out a randomized controlled trial, it is their intention to conduct a study in the cohort of hospitalized patients with covid-19 pneumonia, administering 10 gr of vitamin C intravenously in addition to conventional therapy.

NCT04323514
Conditions
  1. Hospitalized Patients With Covid-19 Pneumonia
Interventions
  1. Dietary Supplement: Vitamin C
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Change of hospital mortality

Measure: In-hospital mortality

Time: 72 hours

Secondary Outcomes

Description: Reduction of PCR levels > 50% in comparison with PCR levels at the admission, within 72 hours after the administration

Measure: PCR levels

Time: 72 hours

Description: Change of the lactate clearance

Measure: Lactate clearance

Time: 72 hours

Description: Change of hospital stay days

Measure: Hospital stay

Time: 72 hours

Description: Resolution of symptoms (Fever, Cough, Shortness of breath or difficulty breathing)

Measure: Symptoms

Time: 72 hours

Description: Change of duration of positive swab (nasopharynx and throat)

Measure: Positive swab

Time: 72 hours

Description: Resolution of tomography imaging (example, patches located in the subpleural regions of the lung)

Measure: Tomography imaging

Time: 72 hours
52 Efficacy and Safety of Chloroquine Diphosphate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV2: a Phase IIb, Double-blind, Randomized Adaptive Clinical Trial

In December 2019, the Municipal Health Committee of Wuhan, China, identified an outbreak of viral pneumonia of unknown cause. This new coronavirus was called SARS-CoV-2 and the disease caused by that virus, COVID-19. Recent numbers show that 222,643 infections have been diagnosed with 9115 deaths, worldwide. Currently, there are no approved therapeutic agents available for coronaviruses. In this scenario, the situation of a global public health emergency and evidence about the potential positive effect of chloroquine (CQ) in most coronaviruses, including SARS-CoV-1, and recent data on small trials on SARS-CoV-2, the investigators intend to investigate the efficacy and the safety of CQ diphosphate in the treatment of hospitalized patients with severe acute respiratory syndrome in the scenario of SARS-CoV2. Preliminary in vitro studies and uncontrolled trials with low number of patients of CQ repositioning in the treatment of COVID-19 have been encouraging. The main hypothesis is that CQ diphosphate will reduce mortality in 50% in those with severe acute respiratory syndrome infected by the SARS-COV2. Therefore, the main objective is to assess whether the use of chloroquine diphosphate reduces mortality by 50% in the study population. The primary outcome is mortality in day 28 of follow-up. According to local contingency plan, developed by local government for COVID-19 in the State of Amazonas, the Hospital Pronto-Socorro Delphina Aziz, located in Manaus, is the reference unit for the admission of serious cases of the new virus. The unit currently has 50 ICU beds, with the possibility of expanding to 335 beds, if needed. The hospital also has trained multiprofessional human resources and adequate infrastructure. In total, 440 participants (220 per arm) will receive either high dose chloroquine 600 mg bid regime (4x150 mg tablets, every 12 hours, D1-D10) or low dose chloroquine 450mg bid regime (3x150mg tablets + 1 placebo tablet every 12 hours on D1, 3x150mg tablets + 1 placebo followed by 4 placebo tablets 12h later from D2 to D5, and 4 placebo tablets every 12 hours, D6-D10). Placebo tablets were used to standardize treatment duration and blind research team and patients. All drugs administered orally (or via nasogastric tube in case of orotracheal intubation). Both intervention and placebo drugs will be produced by Farmanguinhos. Clinical and laboratory data during hospitalization will be used to assess efficacy and safety outcomes.

NCT04323527
Conditions
  1. SARS-CoV Infection
  2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Drug: Chloroquine diphosphate
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

Description: proportion of deaths at day 28 between groups compared

Measure: Mortality rate reduction of 50% by day 28

Time: 28 days after randomization

Secondary Outcomes

Description: number of deaths at days 7 and 14 between groups compared

Measure: Absolute mortality on days 7 and 14

Time: 7 and 14 days after first dose

Description: clinical status

Measure: Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28

Time: 14 and 28 days after first dose

Description: clinical status

Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization

Time: during and after intervention, up to 28 days

Description: supplemental oxygen

Measure: Duration of supplemental oxygen (if applicable)

Time: during and after intervention, up to 28 days

Description: mechanical ventilation

Measure: Duration of mechanical ventilation (if applicable)

Time: during and after intervention, up to 28 days

Description: hospitalization

Measure: Absolute duration of hospital stay in days

Time: during and after intervention, up to 28 days

Description: adverse events grade 3 and 4

Measure: Prevalence of grade 3 and 4 adverse events

Time: during and after intervention, up to 28 days

Description: adverse events

Measure: Prevalence of serious adverse events

Time: during and after intervention, up to 28 days

Description: increase or decrease in serum creatinine compared to baseline

Measure: Change in serum creatinine level

Time: during and after intervention, up to 28 days

Description: increase or decrease in serum troponin I compared to baseline

Measure: Change in serum troponin I level

Time: during and after intervention, up to 28 days

Description: increase or decrease in serum aspartate aminotransferase compared to baseline

Measure: Change in serum aspartate aminotransferase level

Time: during and after intervention, up to 28 days

Description: increase or decrease in serum aspartate aminotransferase compared to baseline

Measure: Change in serum CK-MB level

Time: during and after intervention, up to 28 days

Description: virus clearance from respiratory tract secretion

Measure: Change in detectable viral load in respiratory tract swabs

Time: during and after intervention, up to 28 days

Description: viremia in blood detected through RT-PCR

Measure: Viral concentration in blood samples

Time: during and after intervention, up to 28 days

Description: death

Measure: Absolute number of causes leading to participant death (if applicable)

Time: during and after intervention, up to 28 days
53 Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

COVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution to the lack of ICU beds and increasing deaths day after day. A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically ill patients. Moreover, the Italian Infectious Disease leading institution guidelines for COVID-19 clinical management included as an option for patients with "incipient worsening of respiratory functions" methylprednisolone treatment at an approximate dose of 80mg. The main objective of this multi-centre observational trial is to analyse the association of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome with composite primary end-point (ICU referral, need for intubation, in-hospital death at day 28).

NCT04323592
Conditions
  1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  2. Coronavirus Infections
  3. ARDS, Human
Interventions
  1. Drug: Methylprednisolone
  2. Other: standard care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Distress Syndrome, Adult Syndrome
HPO:Pneumonia

Primary Outcomes

Description: We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.

Measure: Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28

Time: 28 days

Description: We reported below the number of participants who died within 28 days, during the hospital stay.

Measure: In-hospital Death Within 28 Days

Time: 28 days

Description: We reported below the number of participants admitted to ICU within 28 days.

Measure: Admission to Intensive Care Unit (ICU)

Time: 28 days

Description: We reported below the number of participants who needed endotracheal intubation during ICU admission

Measure: Endotracheal Intubation (Invasive Mechanical Ventilation)

Time: 28 days

Secondary Outcomes

Description: Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.

Measure: Change in C-reactive Protein (CRP)

Time: 7 days

Description: number of days free from mechanical ventilation (both invasive and non-invasive) by day 28

Measure: Number of Days Free From Mechanical Ventilation

Time: 28 days
54 Cytokine Adsorption in Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation

In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).

NCT04324528
Conditions
  1. Coronavirus
  2. COVID-19
  3. SARS-CoV Infection
  4. Respiratory Failure
  5. Cytokine Storm
Interventions
  1. Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)
  2. Device: vv-ECMO only (no cytokine adsorption)
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)

Measure: interleukin-6 (IL-6) level after 72 hours

Time: 72 hours

Secondary Outcomes

Description: survival after 30 days

Measure: 30-day-survival

Time: 72 hours

Description: needed dosage of norepinephrine and other vasopressors

Measure: vasopressor dosage

Time: 72 hours

Description: fluid balance levels during cytokine adsorption

Measure: fluid balance

Time: 72 hours

Description: serum-lactate levels during cytokine adsorption

Measure: lactate

Time: 72 hours
55 Time of Recovery and Prognostic Factors of COVID-19 Pneumonia

It has been reported that nearly half of the patients who are hospitalized for Covid-19 pneumonia have on admission old age or comorbidities. In particular, hypertension was present in 30% of the cases, diabetes in 19%, coronary heart disease in 8% and chronic obstructive lung disease in 3% of the patients. Amazingly, in the two major studies published in the Lancet (Zhou F et al Lancet 2020) and in the New England Journal of Medicine (Guan W et al 2020), the weight of the subjects as well their body mass index (BMI) were omitted. However, obesity, alone or in association with diabetes, can be a major predisposition factor for Covid-19 infection. The primary end-point of our prospective, observational study is to assess the recovery rate in patients with diagnosis of Covid-19 pneumonia. Among the other secondary end-points, we intend to find the predictors of the time to clinical improvement or hospital discharge in patients affected by Covid-19 pneumonia.

NCT04324684
Conditions
  1. Pneumonia, Viral
  2. Hypertension
  3. Diabetes Mellitus
  4. Obesity
  5. Cardiovascular Diseases
  6. Obstructive Lung Disease
MeSH:Pneumonia, Viral Pneumonia Lung Diseases Lung Diseases, Obstructive Cardiovascular Diseases
HPO:Abnormal lung morphology Abnormality of the cardiovascular system Pneumonia Pulmonary obstruction

Primary Outcomes

Description: mean rate of recovery in patients with diagnosis of Covid-19 pneumonia, who present with complications at the time of hospital admission (such as diabetes, obesity, cardiovascular disease, hypertension or respiratory failure), with the mean recovery rate in patients without any of the above-mentioned complications.

Measure: rate of recovery

Time: 3 weeks

Secondary Outcomes

Description: comparison of the survival curves (times to improvement) in the two groups (patients with and without complications) and among patients presenting with different types of complications

Measure: time to improvement

Time: 3 weeks

Description: the efficacy of different pharmaceutical treatment against Covid-19

Measure: efficacy of treatments

Time: 3 weeks

Description: liver, kidney or multiorgan failure, cardiac failure

Measure: organ failure

Time: 3 weeks
56 Proflaxis for Healthcare Professionals Using Hydroxychloroquine Plus Vitamin Combining Vitamins C, D and Zinc During COVID-19 Pandemia: An Observational Study

Healthcare professionals mainly doctors, nurses and their first degree relatives (spouse, father, mother, sister, brother, child) who have been started hydroxychloroquine(plaquenil) 200mg single dose repeated every three weeks plus vitaminC including zinc once a day were included in the study. Study has conducted on 20th of march. Main purpose of the study was to cover participants those who are facing or treating COVID19 infected patients in Ankara.

NCT04326725
Conditions
  1. Pneumonitis
  2. Coronavirus Infection
Interventions
  1. Drug: Plaquenil 200Mg Tablet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: persons who took this medication should not have an infection

Measure: Protection against COVID-19

Time: 4 months
57 PCR-COVID-19 Predictors of Positivity in Patients Admitted to ICU for Respiratory Infection: A Prospective Observational Cohort Study

Coronavirus 2019 (COVID-19) is a respiratory tropism virus transmitted through droplets emitted into the environment of infected persons. The symptoms can be extremely varied and the course can range from spontaneous healing without sequelae to death. Currently, the diagnosis of certainty for resuscitation patients (by definition "severe") is based on searching for a fragment of virus genetic material within the epithelial cells of the respiratory tree, up and/or down, by PCR. It is to be expected that the epidemic peak will make it difficult (if not impossible) to respect the stereotypical path that is currently in place, due to the lack of space in the specific unit. This will require optimization of care pathways and use of the specific sectors. It is therefore necessary to define the simple criteria, available from the moment patients are admitted, to predict the result of the COVID-19 PCR.

NCT04327180
Conditions
  1. Infection Viral
  2. Coronavirus
  3. ARDS
  4. Pneumonia
MeSH:Infection Communicable Diseases Virus Diseases Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Correlation between nasal and deep PCR positivity for Covid-19 patients performed and all predictors for Covid-19 patients performed within 24 hours of admission to ICU

Time: within 24 hours of admission to ICU

Secondary Outcomes

Description: Assessment of viral, bacterial, fungal and parasitic rate in confirmed and unconfirmed patients for COVID-19

Measure: Coinfections

Time: during ICU stay, up to 28 days

Description: it will be reported the evolution of respiratory dysfunction in patients infected with COVID-19 admitted to ICU during their stay and requiring mechanical ventilation (during, Pao2/FIO2 ratio,,features of artificial ventilation features of extra-bodied respiratory assistance)

Measure: Respiratory dysfunction requiring mechanical ventilation

Time: during ICU stay, up to 28 days

Description: the SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure).

Measure: Sequential Organ Failure Assessment (SOFA) Score

Time: during ICU stay, up to 28 days

Description: APS II was designed to measure the severity of disease for patients admitted to Intensive care units 24 hours after admission to the ICU, the measurement has been completed and resulted in an integer point score between 0 and 163 and a predicted mortality between 0% and 100%.

Measure: SAPS II score

Time: at admission

Description: The DIC Score was developed by the The International Society of Thrombosis and Haemostasis (ISTH.) The DIC score calculator accounts of the following four parameters.Each of the four parameters evaluated above have values that are weighted with a number of points varying from 0 to 3. By summing the points given to the choices, a final result between 0 and 8 is obtained

Measure: Disseminated Intravascular Coagulation (DIC) score

Time: during ICU stay, up to 28 days

Measure: Number of days on vasopressive amines

Time: during ICU stay, up to 28 days

Measure: Occurrence of an event of venous or arterial thromboembolic disease

Time: during ICU stay, up to 28 days

Measure: Number of days with extra renal treatment (ERA)

Time: during ICU stay, up to 28 days

Measure: Number of patients alive after ICU stay less than 28 days will be tracked

Time: At 28 day

Description: measuring the long-term impact of confirmed COVID-19 infection. assessment of quality of life according to 8 areas: physical activity (and related limitations), body pain, perception of one's own health, mental health (and related limitations), social life and vitality.

Measure: Short Form 36

Time: at 9 months +/- 3 months after ICU stay

Description: The scale allows to detect anxiety and depression using 14 items rated from 0-3. Measuring the long-term impact of confirmed COVID-19 infection

Measure: Hospital anxiety and depression scale (HADS)

Time: at 9 months +/- 3 months after ICU stay

Description: 22-item self-report measure that assesses subjective distress caused by traumatic events Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88) Measuring the long-term impact of confirmed COVID-19 infection

Measure: Impact of Event Scale - revised (IES-R)

Time: at 9 months +/- 3 months after ICU stay

Description: Question the stressful experience or event, followed by 20 multiple-choice questions. Measuring the long-term impact of confirmed COVID-19 infection

Measure: Post-traumatic stress disorder Checklist version DSM-5 (PSL-5)

Time: at 9 months +/- 3 months after ICU stay

Description: The mMRC Dyspnea Scale stratifies severity of dyspnea in respiratory diseases Measuring the long-term impact of confirmed COVID-19 infection

Measure: Modified Medical Research Council (MMRC) Dyspnea Scale

Time: at 9 months +/- 3 months after ICU stay

Measure: Correlation between number of patient deaths and all predictors for Covid-19 including anamnestic, clinical, biological, radiological parameters

Time: until day 28 after admission of ICU

Description: Evolution of viral clearance in nasal and depp PCR during ICU

Measure: Viral clearance

Time: through study completion, an average of 28 days
58 Non-invasive Detection of Pneumonia in Context of Covid-19 Using Gas Chromatography - Ion Mobility Spectrometry (GC-IMS)

On Dec 31, 2019, a number of viral pneumonia cases were reported in China. The virus causing pneumonia was then identified as a new coronavirus called SARS-CoV-2. Since this time, the infection called coronavirus disease 2019 (COVID-19) has spread around the world, causing huge stress for health care systems. To diagnose this infection, throat and nose swabs are taken. Unfortunately, the results often take more than 24 hrs to return from a laboratory. Speeding diagnosis up would be of great help. This study aims to look at the breath to find signs that might allow clinicians to diagnose the coronavirus infection at the bedside, without needing to send samples to the laboratory. To do this, the team will be using a machine called a BreathSpec which has been adapted to fit in the hospital for this purpose.

NCT04329507
Conditions
  1. COVID-19
  2. Respiratory Disease
Interventions
  1. Diagnostic Test: Breath test
MeSH:Pneumonia Respiration Disorders Respiratory Tract Diseases
HPO:Pneumonia

Primary Outcomes

Description: breath sample collection

Measure: To perform a study in patients with clinical features of pneumonia/chest infection to identify a signature of Covid-19 pneumonia in patients exposed to SARS-CoV-2, compared to unexposed patients or those without.

Time: up to daily during hospital admission

Secondary Outcomes

Description: breath sample collection

Measure: Detection of markers of Covid-19 pneumonia in non-invasive breath samples.

Time: multiple samples up to 60 days

Description: breath sample collection

Measure: Relationship of this biomarker signature to the presence of SARS-CoV-2 in nasal and throat swabs.

Time: multiple samples up to 60 days

Description: breath sample collection

Measure: Subsequently, the signature's relationship to other biomarkers of SARS-CoV-2 infection which are currently being explored

Time: multiple samples up to 60 days

Description: breath sample collection

Measure: In a smaller group of participants, ideally daily non-invasive breath samples will be collected to determine if there are changes between SARS-CoV-2 positive patients and those that are negative until hospital discharge or undue participant burden .

Time: multiple samples up to 60 days
59 Phase 2, Randomized, Open-label Study to Compare Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID19 Pneumonia

In our center up to 25% of the hospitalized patients with COVID-19 progress and need an intensive care unit. It is urgent to find measures that can avoid this progression to severe stages of the disease. We hypothesize that the use of anti-inflammatory drugs used at the time they start hyperinflammation episodes could improve symptoms and prognosis of patients and prevent their progression sufficiently to avoid their need for be admitted to an Intensive Care Unit.

NCT04329650
Conditions
  1. COVID-19
Interventions
  1. Drug: Siltuximab
  2. Drug: Methylprednisolone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Proportion of patients requiring ICU admission at any time within the study period.

Time: 29 days

Secondary Outcomes

Measure: Days of stay in the ICU during the study period.

Time: 29 days

Measure: Days until resolution of fever defined as body temperature (axillary ≤ 36.6 ° C, oral ≤ 37.2 ° C, or rectal or tympanic ≤ 37.8 ° C) for at least 48 hours, without administration of antipyretics or until hospital discharge.

Time: 29 days

Measure: Proportion of patients with a worsening requirement of supplemental oxygen at 29 days. days.

Time: 29 days

Measure: Days with hypoxemia (SpO2 <93% in ambient air or requiring oxygen supplemental or mechanical ventilation support) at 29 days.

Time: 29 days

Measure: Proportion of patients using mechanical ventilation at 29 days.

Time: 29 days

Measure: Days with use of mechanical ventilation at 29 days.

Time: 29 days

Measure: Days until the start of use of mechanical ventilation, non-invasive ventilation or use of high flow nasal cannula (if the patient have not previously required these interventions at the inclusion of the study) at 29 days.

Time: 29 days

Measure: Days of hospitalization among survivors at 29 days.

Time: 29 days

Measure: Mortality rate from any cause at 29 days.

Time: 29 days

Measure: Proportion of patients with serious adverse events at 29 days.

Time: 29 days

Measure: Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic with grade 4 neutropenia (count neutrophil absolute <500 / mm3) at 29 days.

Time: 29 days

Measure: Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic at 29 days.

Time: 29 days

Measure: Proportion of patients with grade 2 or higher adverse reactions related to the infusion of the sudy treatments at 29 days.

Time: 29 days

Measure: Proportion of patients with hypersensitivity reactions of grade 2 or higher related to the administration of the study treatments at 29 days.

Time: 29 days

Measure: Proportion of patients with gastrointestinal perforation at 29 days.

Time: 29 days

Measure: Proportion of patients with secondary severe infections confirmed by laboratory or worsening of existing infections at 29 days.

Time: 29 days

Measure: Changes from baseline in plasma leukocyte levels at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Changes from baseline in plasma hemoglobin levels at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Changes from baseline in plasma platelet at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Changes from baseline in plasma creatinine levels at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Changes from baseline in plasma total bilirubin levels at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Proportion of patients with ALT≥ 3 times ULN (for patients with initial values normal) or> 3 times ULN AND at least 2 times more than the initial value (for patients with abnormal initial values) at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Changes from baseline in plasma biomarkers (PCR, lymphocytes, ferritin, d-dimer and LDH) at days 1, 3, 5, 7 and 9.

Time: Days 1, 3, 5, 7 and 9

Measure: Changes from baseline in chest Rx at days 1, 3 and 5.

Time: Days 1, 3 and 5
60 Clinical Characteristics and Outcomes of Children Potentially Infected by Severe Acute Respiratory Distress Syndrome (SARS)-CoV-2 Presenting to Pediatric Emergency Departments

Rationale: The clinical manifestations of SARS-CoV-2 infection in children are poorly characterized. Preliminary findings indicate that they may be atypical. There is a need to identify the spectrum of clinical presentations, predictors of severe disease (COVID-19) outcomes, and successful treatment strategies in this population. Goals: Primary - Describe and compare characteristics of confirmed SARS-CoV-2 infected children with symptomatic test-negative children. Secondary - 1) Describe and compare confirmed SARS-CoV-2 infected children with mild versus severe COVID-19 outcomes; 2) Describe healthcare resource utilization for, and outcomes of, screening and care of pediatric COVID-19 internationally, alongside regional public health policy changes. Methods: This prospective observational study will occur in 50 emergency departments across 11 countries. We will enroll 12,500 children who meet institutional screening guidelines and undergo SARS-CoV-2 testing. Data collection focuses on epidemiological risk factors, demographics, signs, symptoms, interventions, laboratory testing, imaging, and outcomes. Collection will occur at enrollment, 14 days, and 90 days. Timeline: Recruitment will last for 12 months (worst-case model) and will begin within 7-14 days of funding notification after ongoing expedited review of ethics and data sharing agreements. Impact: Results will be shared in real-time with key policymakers, enabling rapid evidence-based adaptations to pediatric case screening and management.

NCT04330261
Conditions
  1. COVID-19
  2. SARS-CoV-2 Infection
  3. Pediatric ALL
  4. Pneumonia, Viral
  5. Pandemic Response
Interventions
  1. Other: Exposure (not intervention) - SARS-CoV-2 infection
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical characteristics among children presenting to a participating hospital's EDs who meet each site's local SARS-CoV-2 screening criteria, will be described and compared between children with confirmed SARS-CoV-2 (i.e. test-positive) versus suspected (i.e. test-negative) infections.

Measure: Clinical characteristics of children with SARS-CoV-2

Time: 18 months

Description: Factors associated with severe outcomes [i.e. positive pressure ventilation (invasive or noninvasive) OR intensive care unit admission with ventilatory or inotropic support OR death; other outcomes may be added as the understanding of the epidemic evolves) will be identified in confirmed paediatric COVID-19 cases.

Measure: Factors associated with severe COVID-19 outcomes

Time: 18 months

Secondary Outcomes

Description: Health care resource utilization for patient management (e.g. frequencies of isolation, laboratory testing, imaging, and supportive care, with associated costs) of both suspected and confirmed SARS-CoV-2 infected children according to changes in national and regional policies.

Measure: Health care resource utilization for COVID-19 patient management

Time: 18 months

Description: The sensitivity and specificity of various case screening policies for the detection of confirmed symptomatic SARS-CoV-2 infection (i.e. COVID-19) in children (e.g. addition of vomiting/diarrhoea).

Measure: Sensitivity and specificity of COVID-19 case screening policies

Time: 18 months
61 Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)

A phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.

NCT04331613
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Virus; Pneumonia
  4. Acute Lung Injury
Interventions
  1. Biological: CAStem
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment

Measure: Adverse reaction (AE) and severe adverse reaction (SAE)

Time: Within 28 days after treatment

Description: Evaluation by chest CT

Measure: Changes of lung imaging examinations

Time: Within 28 days after treatment

Secondary Outcomes

Description: Marker for SARS-CoV-2

Measure: Time to SARS-CoV-2 RT-PCR negative

Time: Within 28 days after treatment

Description: The duration of a fever above 37.3 degrees Celsius

Measure: Duration of fever (Celsius)

Time: Within 28 days after treatment

Description: Marker for efficacy

Measure: Changes of blood oxygen (%)

Time: Within 28 days after treatment

Description: Marker for efficacy

Measure: Rate of all-cause mortality within 28 days

Time: Within 28 days after treatment

Description: Counts of lymphocyte in a litre (L) of blood

Measure: Lymphocyte count (*10^9/L)

Time: Within 28 days after treatment

Description: Alanine aminotransferase in unit (U)/litre(L)

Measure: Alanine aminotransferase (U/L)

Time: Within 28 days after treatment

Description: Creatinine in micromole (umol)/litre(L)

Measure: Creatinine (umol/L)

Time: Within 28 days after treatment

Description: Creatine kinase in U/L

Measure: Creatine kinase (U/L)

Time: Within 28 days after treatment

Description: C-reactive in microgram (mg)/litre(L)

Measure: C-reactive protein (mg/L)

Time: Within 28 days after treatment

Description: Procalcitonin in nanogram (ng)/litre(L)

Measure: Procalcitonin (ng/L)

Time: Within 28 days after treatment

Description: Lactate in millimole(mmol)/litre(L)

Measure: Lactate (mmol/L)

Time: Within 28 days after treatment

Description: IL-1beta in picogram(pg)/millilitre(mL)

Measure: IL-1beta (pg/mL)

Time: Within 28 days after treatment

Description: IL-2 in pg/mL

Measure: IL-2 (pg/mL)

Time: Within 28 days after treatment

Description: IL-6 in pg/mL

Measure: IL-6 (pg/mL)

Time: Within 28 days after treatment

Description: IL-8 in pg/mL

Measure: IL-8 (pg/mL)

Time: Within 28 days after treatment
62 A Single Arm Open-label Clinical Study to Investigate the Efficacy and Safety of Ruxolitinib for the Treatment of COVID-19 Pneumonia

The purpose of this study is to determine the safety and efficacy of the drug ruxolitinib in people diagnosed with COVID-19 pneumonia by determining the number of people whose conditions worsen (requiring machines to help with breathing or needing supplemental oxygen) while receiving the drug. This is a sub-study of the U-DEPLOY study: UHN Umbrella Trial Defining Coordinated Approach to Pandemic Trials of COVID-19 and Data Harmonization to Accelerate Discovery. U-DEPLOY helps to facilitate timely conduct of studies across the University Health Network and other centers.

NCT04331665
Conditions
  1. COVID-19
  2. Pne
  3. Pneumonia
Interventions
  1. Drug: Ruxolitinib
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Proportion of patients with COVID-19 pneumonia who become critically ill (defined as requiring mechanical ventilation and/or FiO2 of 60% of more)

Time: 6 months

Measure: Number of adverse events

Time: 9 months

Secondary Outcomes

Measure: All cause mortality rate

Time: 9 months

Measure: Average duration of hospital stay

Time: 9 months
63 Early Institution of Tocilizumab Titration in Non-Critical Hospitalized COVID-19 Pneumonitis

Coronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. Hypotheses: 1. Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death. 2. Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death. Objectives: 1. To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize. 2. To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.

NCT04331795
Conditions
  1. COVID-19
Interventions
  1. Drug: Tocilizumab
  2. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Tmax Response: Resolution of fever (from Tmax > 38C in 24H period to Tmax < 38C in following 24H period, with Tmax measured by commonly accepted clinical methods [forehead, tympanic, oral, axillary, rectal]). Maximum temperature within 24-hour period of time (0:00-23:59) on the day prior to, day of, and every 24 hours after tocilizumab administration. The primary endpoint is absence of Tmax greater than or equal to 38ºC in the 24-hour period following tocilizumab administration.

Measure: Clinical response

Time: Assessed for the 24 hour period after tocilizumab administration

Description: CRP normalization rate: Calculated as the ratio of the number of patients who achieve normal CRP value following tocilizumab administration and total number of patients who receive tocilizumab. Time to CRP normalization: Calculated as the number of hours between tocilizumab administration and first normal CRP value.

Measure: Biochemical response

Time: Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administration

Secondary Outcomes

Description: 28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.

Measure: Overall survival

Time: 28 days

Description: This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.

Measure: Survival to hospital discharge

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).

Measure: Progression of COVID-19 pneumonitis

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.

Measure: Rate of non-elective mechanical ventilation

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).

Measure: Duration of mechanical ventilation

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.

Measure: Time to mechanical ventilation

Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.

Measure: Rate of vasopressor/inotrope utilization

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).

Measure: Duration of vasopressor/inotrope utilization

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.

Measure: Time to vasopressor or inotropic utilization

Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration

Description: Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.

Measure: Number of ICU days

Time: Hospitalization, up to 4 weeks after tocilizumab administration

Description: Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.

Measure: Duration of Increased Supplemental Oxygen Requirement from Baseline

Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration
64 TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia

Immune-mediated lung injury plays a pivotal role in severe interstitial pnemumonia related to SARS-CoV2 infection. Tofacitinib, a JAK1/3-Inhibitor, could mitigate alveolar inflammation by blocking IL-6 signal. The aim of this prospective single cohort open study is to test the hypotesis that early administration of tofacitinib in patients with symptomatic pneumonia could reduce pulmonary flogosis, preventing function deterioration and the need of mechanical ventilation and/or admission in intensive care units.

NCT04332042
Conditions
  1. SARS-COv2 Related Interstitial Pneumonia
Interventions
  1. Drug: Tofacitinib
MeSH:Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150 or, if PaO2 data not available, to maintain SO2>94% with FiO2 0,5.

Measure: need of mechanical ventilation

Time: day 14

Secondary Outcomes

Description: Rate of patients needing admission to the intensive care unit for oro-tracheal intubation and/or evidence of Multiple Organ Disfunction

Measure: need of admission in intensive care unit

Time: day 14

Description: rate of patients dead

Measure: death

Time: day 28

Description: rate and type of adverse events

Measure: rate of adverse events

Time: day 28
65 Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study

The current spread of the COrona VIrus Disease-2019 (COVID-19) epidemic in Italy, and the current lack of effective and approved drugs for its treatment, poses the problem of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients management, especially those who underwent to experience COVID-19 complications, such as CRS. This unmet need becomes more severe if the investigator consider that, the COVID-19 mortality stands around 2% in the general population, but it rises to 49% when considering intensive care unit (ICU) patients. To increase the chances of survival of these patients, the compassionate use of the available drugs is required, based on literature data, to the best of our abilities. ICU patients with cytokine release syndrome (CRS) secondary to COVID-19, show increased production of pro-inflammatory cytokines, including interleukin (IL-6), IL-2, IL-7, IL-10, tumor necrosis factor (TNF)-α and interferon (INF)γ, similar to that found in patients who develop CRS secondary to Chimeric Antigen Receptor-T (CAR-T) therapy. Although immuno-modulatory therapy is not routinely recommended in COVID-19 pneumonia, tocilizumab might have a rationale in those patients who develop CRS, blocking the complications caused by high levels of IL-6, and possibly preventing the development of a multi-organ failure. Reassuring data in this sense, come from the first studies conducted in China. In a Chinese pilot study, Xiaoling Xu and collaborators used tocilizumab (at a dosage of 400 mg iv in a single dose, with a possible second dose in case of no clinical response) in patients with COVID-19 in the presence of one of the following criteria: i) respiratory rate ≥ 30 acts/min; ii) SpO2 ≤ 93% in ambient air; iii) PaO2/FiO2 ≤ 300 mmHg. In the 21 patients treated with tocilizumab a significant reduction in IL-6 levels and fever, with improvement in lung function, was demonstrated. Besides, 90% of treated patients showed an improvement in the radiological picture, in terms of a decrease in the frosted glass areas, and a return to normal lymphocytes count in the peripheral blood. This is a prospective observational clinical study and it is aimed at verifying tocilizumab efficacy and safety in patients with COVID-19 complicated by acute distress respiratory syndrome (ARDS) and CRS.

NCT04332913
Conditions
  1. COVID-19 Pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours; SpO2 normalization criterion: SpO2> 94% for at least 72 hours

Measure: Percentage of patients with complete recovery defined as fever disappearance and return to normal peripheral oxygen saturation values (SpO2) after 14 days from the end of treatment with tocilizumab.

Time: 14 days

Secondary Outcomes

Measure: Percentage of patients achieving a score <3 on the Brescia-COVID respiratory severity scale (BCRSS) after the last tocilizumab administration.

Time: 24 hours

Description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours

Measure: Percentage of patients with partial recovery defined as the disappearance of fever 14 days after the end of treatment with tocilizumab.

Time: 14 days

Description: days

Measure: Duration of hospitalization

Time: 14 days

Description: days

Measure: Time to the first negative SARS-CoV-2 negative RT-PCR test

Time: 14 days

Description: number/microliter

Measure: Changes from the baseline in the white blood cell count

Time: 7, 14 days

Description: number/microliter

Measure: Changes from the baseline in the lymphocyte populations (cluster of differentiation (CD)3+CD4+, CD3+CD8+, CD19+, Th17)

Time: 7, 14 days

Measure: Changes from the baseline of c-reactive protein (CRP) values

Time: 7, 14 days

Measure: Changes from the baseline of Ferritin values

Time: 7, 14 days

Measure: Changes from the baseline of BNP values

Time: 7,14 days

Measure: Changes from the baseline of CK-MB values

Time: 7,14 days

Measure: Changes from the baseline of Troponin values

Time: 7,14 days

Measure: Changes from the baseline of LDH values

Time: 7,14 days

Measure: Changes from the baseline of myoglobulin values

Time: 7,14 days

Description: (ST segments elevation or depression, T-wave changes)

Measure: Changes in myocardial ischemia signs at the electrocardiographic trace (YES or NO)

Time: 7,14 days

Measure: Rate of adverse events report during and after tocilizumab

Time: 14 days

Measure: Mortality (number of Partecipants, cause and timing)

Time: 12 weeks

Measure: Percentage of patients who develop autoimmune diseases

Time: 1 year
66 Evaluating Convalescent Plasma to Decrease Coronavirus Associated Complications. A Phase I Study Comparing the Efficacy and Safety of High-titer Anti-Sars-CoV-2 Plasma vs Best Supportive Care in Hospitalized Patients With Interstitial Pneumonia Due to COVID-19

Currently there are no proven treatment option for COVID-19. Human convalescent plasma is an option for COVID-19 treatment and could be available from people who have recovered and can donate plasma.

NCT04333251
Conditions
  1. Pneumonia, Interstitial
Interventions
  1. Biological: high-titer anti-Sars-CoV-2 plasma
  2. Other: oxygen therapy
MeSH:Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: reduction in oxygen and ventilation support

Measure: reduction in oxygen and ventilation support

Time: through study completion, an average of 4 weeks
67 A Pragmatic Adaptive Randomized, Controlled Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia

Phase II & Phase III: This is a pragmatic, adaptive, randomized, multicenter phase II/III study evaluating IFX-1 for the treatment of COVID-19 related severe pneumonia. The study consists of two parts: Phase II, an open-label, randomized, 2-arm phase evaluating best supportive care (BSC) + IFX-1 (Arm A) and BSC alone (Arm B); and Phase III, a double-blind, placebo-controlled, randomized phase comparing standard of care (SOC) + IFX-1 (Arm A) versus SOC + placebo-to-match (Arm B)

NCT04333420
Conditions
  1. Severe COVID-19 Pneumonia
Interventions
  1. Drug: SOC + IFX-1
  2. Drug: SOC + Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: 28-day all-cause mortality

Measure: Mortality

Time: Day 28

Secondary Outcomes

Description: Frequency, severity, and relatedness to study drug of serious and non-serious TEAEs

Measure: Treatment Emergent Adverse Events

Time: Day1 to Day 60

Description: Proportion of patients with an improvement in the 8-point ordinal scale

Measure: Safety Parameters

Time: Day 15, Day 28
68 Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia : a Multicenter, Parallel-group, Open-label, Randomized Controlled Trial

The novel coronavirus SARS-CoV-2 (COVID-19) is an emerging respiratory virus that causes pneumonia. WHO data reported admission to the intensive care unit (ICU) for 6% of patients, with a mortality rate reaching 45%. To date, apart from therapeutic trials, ICU management is symptomatic, based on organ failure support therapies. In the initial phase, the therapeutic management also includes empiric antimicrobial therapy (90% of patients, in accordance with LRTI guidelines (ATS 2019) and SRLF Guidelines (2020). One challenge for the ICU physicians is the timing for discontinuation of antimicrobial treatment, especially in case of shock or ARDS, considering that a substantial proportion of COVID-19 pneumonia patients may have pulmonary bacterial coinfection/superinfection. In order to avoid unnecessary prolonged antimicrobial therapy, and subsequent selective pressure, two tests could be combined in a personalized antibiotic strategy: - Procalcitonin (PCT): PCT is a useful tool to guide antibiotics discontinuation in community-acquired pneumonia) and viral pneumonia (PMID24612487). - Respiratory multiplex PCR FA-PPP (Biomérieux®): panel has been enlarged, including 8 viruses and 18 bacteria (quantitative analysis). The turnaround time is short. Sensitivity is high (99%, PMID32179139). It may contribute, in combination with conventional tests, to accelerate and improve the microbiological diagnosis during severe COVID-19 pneumonia. The hypothesize of the study is that the combination of the mPCR FA-PPP and PCT could be used to reduce antibiotics exposure in patients with severe confirmed COVID-19 pneumonia, with a higher clinical efficacy and safety as compared with a conventional strategy.

NCT04334850
Conditions
  1. Covid19
  2. Pneumonia
Interventions
  1. Procedure: Combined use of a respiratory broad panel multiplex PCR and procalcitonin
  2. Other: Usual antibiotic treatment
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: the number of days alive without any antibiotics at Day 28. The D28 time point is usual in studies assessing antibiotics saving in ICU patients.

Measure: Number of antibiotic free days

Time: Day 28

Secondary Outcomes

Measure: Mortality rates

Time: Day 28 and Day 90

Measure: Number of defined daily dose (DDD) per 100 patient-days of broad- and narrow-spectrum antibiotics.

Time: day 28

Description: Total exposure to antibiotics

Measure: Antibiotics duration at D28

Time: Day 28

Measure: Number of organ-failure free days (based on SOFA)

Time: Day 28

Measure: Incidence rates of bacterial super-infections

Time: day 28

Measure: Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections

Time: Day 28

Measure: ICU and hospital lengths of stay

Time: Day 28

Description: using a quality of life questionnaire (EQ5D5L)

Measure: Quality of life Quality of life

Time: Day 90
69 Interest of the Use of Pulmonary Ultrasound in the Referral of Patients With or Suspected COVID-19 +

The recent pandemic due to the SARS-CoV2 results in a pulmonary infection in major symptomatic patients. Because of the large number of patients and the risk of acute respiratory distress syndrome (which seems to occur in almost 5% of patients), there is a real challenge to improve physician ability to screen between patients those who will require specific surveillance and those who can be sent back home. The recent French official recommendation of the French radiology society prescribe that chest X-ray do not have any place in the COVID-19+ management whereas the WHO stipulate that ultrasound machines may be useful for these patients [1-2]. Moreover, scattered recent publications tend to stress the interest of quick ultrasound imaging for COVID-19 suspected patients for screening purpose [2-5]. The aim of this observational historico-prospective study is to assess the risk of severe clinical outcomes (admission in continuous care unit (USC), invasive respiratory assistance, death) in patients suspected or diagnosed COVID-19+ as a function of initial pulmonary ultrasound abnormalities. These clinical outcomes are assessed through phone calls at D5, D15, M1. The secondary objectives are: - Assessing the concordance between the severity of pulmonary lesions as detected by pulmonary ultrasound devices and the ones detected by CT-scanner, for patients who will undergo these two examinations. - Assessing the compared performances in detecting ultrasound pulmonary lesions for patients suspected or diagnosed COVID-19+, between an experimented operator and a newly trained operator.

NCT04335019
Conditions
  1. 2019-nCoV (COVID-19)
  2. Interstitial Pneumonia
Interventions
  1. Other: Pulmonary ultrasound
MeSH:Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Association of pulmonary lesions on ultrasound on D0 classified according to three stages of severity There are few B lines at the lung bases Bi-lateralization of B lines, numerous diffuse and / or curtain sign Presence of signs of pulmonary consolidation, hepatization of the lung and air bronchogram)

Measure: Association of pulmonary lesions on ultrasound on D0 classified according to three stages of severity

Time: at day0

Secondary Outcomes

Measure: Assessment of the agreement between a newly trained operator and an experienced operator of classification in one of the three stages of ultrasound gravity, by Cohen's kappa coefficient.

Time: at day0

Measure: Estimate in patients who had a CT-scan on D0, the agreement in the evaluation of the severity of lung lesions via ultrasound vs. CT-scan, by Cohen's kappa coefficient

Time: at day0

Measure: Measurement of the cumulative incidence of invasive mechanical ventilation and measurement of survival

Time: at day5

Measure: Measurement of the cumulative incidence of invasive mechanical ventilation and measurement of survival

Time: at day15

Measure: Measurement of the cumulative incidence of invasive mechanical ventilation and measurement of survival

Time: at day28
70 Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia

Phase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study

NCT04335201
Conditions
  1. Patients With COVID-19 Pneumonia Will Allow to Detect an Absolute Reduction in the Rate of Respiratory-failure
Interventions
  1. Drug: Defibrotide Injection
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: To demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines (protease inhibitors antiviral treatment and hydroxychloroquine (HCQ), and if needed, metilprednisolone is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia. Patients with a baseline PaO2/FiO2 >= 200: progression of respiratory failure is defined by: severe gas transfer deficit (PaO2/FiO2 < 200); persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements); transfer to the intensive care unit; death. The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+14 from treatment start.

Measure: to able to reduce the progression of acute respiratory failure

Time: 14 days

Secondary Outcomes

Description: To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0

Measure: Adverse events

Time: 7 days

Description: evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection

Measure: duration of hospitalization

Time: 14 days

Description: To evaluate the level of PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3 at day +7 and +14 after start of treatment with Defibrotide. performed per day. Laboratory values performed at day 7 and 14 will be analyzed and compared with each other to understand their progress.

Measure: systemic inflammation

Time: 14 days

Description: To evaluate the overall survival at day+28 after start treatment with Defibrotide

Measure: overall survival

Time: 28 days
71 A Randomized, Controlled, Open-Label, Phase II Trial to Evaluate the Efficacy and Safety of Tocilizumab Combined With Pembrolizumab (MK-3475) in Patients With Coronavirus Disease 2019 (COVID-19)-Pneumonia

This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial

NCT04335305
Conditions
  1. COVID-19
  2. Pneumonia, Viral
Interventions
  1. Drug: Tocilizumab
  2. Biological: Pembrolizumab (MK-3475)
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Assessed by hospital records

Measure: Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes

Time: through day 14 after study treatment initiation

Secondary Outcomes

Description: Assessed by hospital records

Measure: Proportion of patients discharged from the emergency department and classified as low risk

Time: through End of Study, defined as 90 ± 14 days after study entry

Description: Assessed by hospital records

Measure: Number of days of patient hospitalization

Time: through End of Study, defined as 90 ± 14 days after study entry

Description: The clinical status will be assessed by the SOFA scores

Measure: Change from baseline in organ failure parameters

Time: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first.

Description: Determined as percentage of dead patients

Measure: Proportion of mortality rate

Time: through End of Study, defined as 90 ± 14 days after study entry

Description: Determined as: Time to invasive mechanical ventilation (if not previously initiated); Time to independence from non-invasive mechanical ventilation; Time to independence from oxygen therapy.

Measure: Analysis of the remission of respiratory symptoms

Time: through End of Study, defined as 90 ± 14 days after study entry

Description: by using the same imaging technique (chest X-ray or thoracic CT scan)

Measure: Evaluation of the radiological response

Time: at days 1 and 28 (+/- 2 days)

Description: determined using oropharyngeal or anal swabs

Measure: Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test

Time: within 28 days from study inclusion

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of hemoglobin

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of platelets

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of activated partial thromboplastin time (aPTT)

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of creatinine

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of glucose

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of total bilirubin

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

Measure: Change from baseline of albumin

Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

Description: Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.

Measure: Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability)

Time: Up to End of Study, defined as 90 ± 14 days after study entry
72 Outcomes of Patients With COVID-19 in the Intensive Care Unit: A National Observational Study (Mexico COVID-19 ICU Study)

The objective of this study is to evaluate the clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to the intensive care unit. A Multicenter Observational Study.

NCT04336345
Conditions
  1. Coronavirus Infections
  2. COVID-19
  3. Viral Pneumonia Human Coronavirus
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Mortality 30 days following hospital admission

Measure: Hospital mortality

Time: 30 days

Secondary Outcomes

Description: The number of calendar days from the day of admission (counted as 1 day) to day of intensive care unit discharge

Measure: Length of stay in the intensive care unit

Time: Through study completion, an average of 30 days
73 Accuracy and Inter-observer Variability of Lung Ultrasound in COVID-19 Pneumonia

COVID-19 is a rapidly spreading and very contagious disease caused by a novel coronavirus that can lead to respiratory insufficiency. In many patients, the chest radiograph at first presentation be normal, and early low-dose CT-scan is advocated to diagnose viral pneumonia. Lung ultrasound (LUS) has similar diagnostic properties as CT for diagnosing pneumonia. However, it has the advantage that it can be performed at point-of-care, minimizing the need to transfer the patient, reducing the number of health care personnel and equipment that come in contact with the patient and thus potentially decrease the risk of spreading the infection. This study has the objective to examine the accuracy of lung ultrasound in patients with proven COVID-19 pneumonia.

NCT04338568
Conditions
  1. COVID-19 Pneumonia
  2. Lung Ultrasound
Interventions
  1. Diagnostic Test: Lung ultrasound
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The diagnostic accuracy of lung ultrasound is more than 90% compared to low-dose CT or chest X-ray for the detection of viral pneumonia in patients with COVID-19 infection.

Measure: Accuracy of the diagnosis of interstitial syndrome by lung ultrasound

Time: within 2 weeks after first subject included

Description: The interobserver variability by lung ultrasound between the 2 observers for the diagnosis of interstitial syndrome by lung ultrasound is > 0.6 measured by the Kappa score

Measure: Inter-observer variability

Time: within 2 weeks after first subject included
74 Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia

The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.

NCT04339660
Conditions
  1. COVID-19
Interventions
  1. Biological: UC-MSCs
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Improvement and recovery time of inflammatory and immune factors

Measure: The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP)

Time: Observe the immune function of the participants within 4 weeks

Description: Evaluation of Pneumonia change

Measure: Blood oxygen saturation

Time: Monitor blood oxygen saturation of the participants within 4 weeks

Secondary Outcomes

Description: Marker for efficacy of treatment

Measure: Rate of mortality within 28-days

Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

Description: Evaluation of Pneumonia change

Measure: Size of lesion area by chest imaging

Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

Description: Marker of Immunology and inflammation

Measure: CD4+ and CD8+ T cells count

Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

Description: Degree of infection

Measure: Peripheral blood count recovery time

Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

Description: Indirect response to lung function

Measure: Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.)

Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

Description: Clearance time of COVID-19 in participant

Measure: COVID-19 nucleic acid negative time

Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
75 French Multicentre Observational Study on SARS-Cov-2 Infections (COVID-19) ICU Management: the FRENCH CORONA Study

Since December 2019, a new agent, the SARS-Cov-2 coronavirus has been rapidly spreading from China to other countries causing an international outbreak of respiratory illnesses named COVID-19. In France, the first cases have been reported at the end of January with more than 60000 cases reported since then. A significant proportion (20-30%) of hospitalized COVID-19 patients will be admitted to intensive care unit. However, few data are available for this special population in France. We conduct a large observational cohort of ICU suspected or proven COVID-19 patients that will enable to describe the initial management of COVID 19 patients admitted to ICU and to identify factors correlated to clinical outcome.

NCT04340466
Conditions
  1. Pneumonia, Viral
  2. Critically Ill
  3. Corona Virus Infection
Interventions
  1. Other: No intervention
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Cr Critical Illness
HPO:Pneumonia

Primary Outcomes

Description: Mortality at day 28

Measure: Mortality at day 28

Time: day 28

Secondary Outcomes

Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No

Measure: severe complications

Time: up to day 28

Description: Delay in imaging in hours

Measure: Imaging

Time: day 1

Description: delay in microbiological diagnosis in hours

Measure: Delay in Microbiological diagnosis

Time: day 1

Description: Antiviral therapy Yes / no

Measure: Antiviral therapy

Time: up to day 28

Description: Antibiotic therapy Yes / No

Measure: Antibiotic therapy

Time: day 28

Description: Covid-19 treatments Yes / No

Measure: Covid-19 treatments

Time: up to day 28

Description: number

Measure: Patients receiving renal replacement therapy

Time: up to day 28

Description: number

Measure: Patients receiving mechanical ventilation

Time: up to day 28

Description: Patient alive at day 28 : yes / No

Measure: Vital status

Time: day 28
76 "Psychological Burden in ICU Survivors of Severe COVID-19 Pneumonia, Their Relatives and Their Healthcare Providers" "Impact Psychologique de l'épidémie COVID-19 Chez Les Patients, Familles et Soignants de Reanimation" "BURDENCOV"

Coronavirus disease 2019 (COVID-19) is an infectious disease responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is highly contagious requiring restrictive and stressful measures for patients, family members and ICU healthcare providers. To avoid contagion, patient isolation has become the rule. For patients, these measures add stress to the ICU environment and deprive them of unrestricted family visits. Family members are not only left with fear but also many unanswered questions. In end-of-life situations, many family members are unable to say good-bye and unable to provide support to their loved-one throughout the process. The impact of exclusion or limited inclusion certainly needs to be explored. Moreover, ICU caregivers are having to face new challenges and to work in a unknown situation, juggling with both professional issues such as increased workload, working longer hours and safety issues, and personal issues such as child care and transport as well as family transmission of the virus. The main objective of this study is to demonstrate that the COVID-19 pandemic, as compared to seasonal flu and community acquired pneumonia, significantly increases post-traumatic stress disorder (PTSD) in family members of critically ill patients. PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge. The IES-R is a 22-item self-report measure that assesses subjective distress caused by traumatic events. It will be compared across the three groups (COVID-19, FLU and CAP).

NCT04341519
Conditions
  1. Corona Virus Infection
  2. Post-traumatic Stress Disorder
Interventions
  1. Behavioral: PTSD
  2. Behavioral: Burnout
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Stress Disorders, Traumatic Stress Disorders, Post-Traumatic
HPO:Pneumonia

Primary Outcomes

Description: Proportion of Family members with IES-R> 22 PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge of corresponding patient. It si a scale ranging from 0 to 88. Weiss, DS.; Marmar, CR. The impact of event scale - revised. In: Wilson, JP.; Keane, TM., editors.Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. p. 399-411

Measure: PTSD Family members sup 22

Time: 90 days

Secondary Outcomes

Description: Among Family members PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

Measure: PTSD Family members

Time: 90 days

Description: Among Patients PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

Measure: PTSD Patients

Time: 90 days

Description: Among healthcare providers PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

Measure: PTSD healthcare providers

Time: 2 months after official end of the Covid-19 peak

Description: Among Family members Symptoms of anxiety and depression using the HADS scale

Measure: HADS Family members

Time: 90 days

Description: Among Patients Symptoms of anxiety and depression using the HADS scale

Measure: HADS Patients

Time: 90 days

Description: Among Patients Mental and physical health-related quality of life as assessed by the SF36

Measure: SF36 Patients

Time: 90 days

Description: Among Family members Questionnaire describing their experience of the patient's ICU hospitalization

Measure: Questionnaire Family members

Time: 90 days

Description: Among Patients Questionnaire describing their experience of the patient's ICU hospitalization

Measure: Questionnaire Patients

Time: 90 days

Description: Among healthcare providers Questionnaire describing their experience of the patient's ICU hospitalization

Measure: Questionnaire healthcare providers

Time: 2 months after official end of the Covid-19 peak

Description: Among healthSymptoms of burnout on MBI scale as assessed by the Maslash Burnout Inventorycare providers

Measure: MBI healthcare providers

Time: 2 months after official end of the Covid-19 peak

Description: Job Strain as assessed by the Karasec instrument

Measure: Karasec instrument healthcare providers

Time: 2 months after official end of the Covid-19 peak
77 Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (The SCOPE Trial)

The main objective of our study is to determine if treatment with sirolimus can improve clinical outcomes in hospitalized patients with COVID-19. The investigators will employ a randomized, double blind, placebo-controlled study design. 30 subjects will be randomized in a 2:1 fashion to receive sirolimus or placebo. Sirolimus will be given as a 6mg oral loading dose on day 1 followed by 2mg daily for a maximum treatment duration of 14 days or until hospital discharge, whichever happens sooner. Chart reviews will be conducted daily to determine changes in clinical status, concomitant medications and laboratory parameters. Study specific biomarkers will be measured at baseline and then at days 3, 7 and 14.

NCT04341675
Conditions
  1. COVID-19
Interventions
  1. Drug: Sirolimus
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group. * CPAP use for known obstructive sleep apnea will not be considered as disease progression.

Measure: Proportion of patients who are alive and free from advanced respiratory support measures at day 28.

Time: 28 days

Secondary Outcomes

Description: Progression to a higher level of care, e.g. ICU

Measure: Proportion of patients who require escalation in care

Time: 14 days

Description: Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)

Measure: Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)

Time: 14 days

Description: Survival to hospital discharge

Measure: Proportion of patients surviving to hospital discharge

Time: days

Description: Incidence and type of adverse events

Measure: Drug safety profile

Time: 14 days

Description: Number of days spent on advanced respiratory support measures

Measure: Duration of advanced respiratory support

Time: days

Description: Length of hospitalization (in patients who survive to discharge)

Measure: Duration of hospital stay

Time: days

Description: Number of days between study initiation and death (in the subset of patients who die during the hospitalization)

Measure: Time from treatment initiation to death

Time: days

Description: Time (in days) to resolution of fever

Measure: Time to resolution of fever

Time: 14 days

Description: Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians

Measure: Proportion of patients who require initiation of off-label therapies

Time: 14 days
78 Prospective Descriptive Study on the Evolution of Pulmonary Ultrasound in Patients Hospitalized for Covid19

Clinical thoracic ultrasound plays an important role in the exploration, diagnosis and follow-up of thoracic pathologies. The COVID (Coronavirus Disease) epidemic is leading to a large influx of patients in the emergency department with respiratory disorders. The rapid diagnosis of respiratory disorders in infected patients is important for further management. Chest ultrasound has already demonstrated its value in the diagnosis of pneumonia in the emergency department with superiority over chest X-ray. However, there is little data on the thoracic ultrasound semiology of viral pneumonia in general and of COVID in particular.

NCT04341766
Conditions
  1. Pneumonia, Viral
  2. COVID-19
Interventions
  1. Other: No special intervention
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: description of ultrasound abnormalities for Covid-19 patients

Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

Time: Day one

Secondary Outcomes

Description: description of ultrasound abnormalities for Covid-19 patients

Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

Time: Day 3

Description: description of ultrasound abnormalities for Covid-19 patients

Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

Time: Day 14

Description: description of CT-scan abnormalities for Covid-19 patients

Measure: Charateristics of pulmonary CT-scan for Covid-19 patients

Time: Day 1

Description: description of CT-scan abnormalities for Covid-19 patients

Measure: Charateristics of pulmonary CT-scan for Covid-19 patients

Time: Day 3

Description: description of CT-scan abnormalities for Covid-19 patients

Measure: Charateristics of pulmonary CT-scan for Covid-19 patients

Time: Day 14
79 Phase IIb Study to Evaluate the Efficacy and Safety of Chloroquine Diphosphate in the Treatment of Patients With Comorbidities, Without Severe Acute Respiratory Syndrome, Under the New Coronavirus (SARS-CoV2): a Double-blind, Randomized, Placebo-controlled Clinical Trial

This is a double-blind, randomized, placebo-controlled clinical trial. A total of 210 individuals aged over 18 years old, without a diagnosis of severe respiratory disease, who came to the study site with clinical and radiological suspicion of SARS-CoV2, will be randomized into two treatment groups at a 1:1 ratio to receive a 5-day CQ diphosphate tablets or placebo (tablet without active ingredient produced with the same physical characteristics).

NCT04342650
Conditions
  1. COVID-19
  2. SARS-CoV Infection
  3. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  4. Clinical Trial
Interventions
  1. Drug: Chloroquine Diphosphate
  2. Drug: Placebo oral tablet
MeSH:Infection Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Evaluate if CQ diphosphate prevents the onset of SARS in patients on intervention group through standardized questionnaires.

Measure: Proportion of patients with onset of severe acute respiratory syndrome (SARS)

Time: 7 days after randomization

Secondary Outcomes

Description: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization

Measure: Mortality rate

Time: after randomization, up to 28 days

Description: Proportion of participants in need and duration of intensive care support after randomization

Measure: Number of participants in need of intensive care support

Time: during and after intervention, up to 28 days

Description: Viral load change in blood and oropharyngeal swab samples

Measure: Viral concentration

Time: After randomization, up to 7 days

Description: Incidence of serious adverse events during and after treatment

Measure: Cumulative incidence of serious adverse events

Time: During and after intervention, up to 28 days

Description: Incidence of grade 3 and 4 adverse events during and after treatment

Measure: Cumulative incidence of grade 3 and 4 adverse events

Time: During and after intervention, up to 28 days

Description: proportion of discontinuation or temporary suspension of treatment (for any reason)

Measure: Proportion of patients with discontinued treatment

Time: after randomization, up to 28 days

Description: proportion of patients with increased levels of troponin I

Measure: Incidence of cardiac lesions

Time: after randomization, up to 120 days

Description: proportion and magnitude of QTcF interval increases higher than 500ms

Measure: Incidence of cardiac disfunctions

Time: after randomization, up to 120 days

Description: Changes measured on day 120 will be compared to baseline, through spirometry.

Measure: Change in respiratory capacity

Time: Day 120 after randomization
80 A Randomized, Double-blind, Placebo-controlled, Clinical Trial of LY3127804 in Patients Who Are Hospitalized With Pneumonia and Presumed or Confirmed COVID-19

A randomized, double-blind, placebo-controlled, clinical trial of LY3127804 in participants who are hospitalized with pneumonia and presumed or confirmed COVID-19. The study may last up to 9 weeks and include daily visits up to day 28, and follow-up visits by phone.

NCT04342897
Conditions
  1. COVID-19
  2. Pneumonia
Interventions
  1. Drug: LY3127804
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of days on which a participant breathes without assistance

Measure: Number of Ventilator Free Days

Time: Day 1 to Day 28

Secondary Outcomes

Description: The scale is an assessment of clinical status. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities

Measure: Number of Participants Reporting Each Severity Rating on the National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Assessment

Time: Day 1 to Day 28

Description: Survival without Respiratory Failure

Measure: Percentage of Participants who are Alive and Respiratory Failure Free

Time: Day 1 to Day 28

Description: Mortality

Measure: Mortality

Time: Day 1 to Day 28

Description: Days of Hospitalization

Measure: Length of Hospitalization

Time: Day 1 to Day 28

Description: Number of Participants with any Serious Adverse Event (SAE)

Measure: Number of Participants with any Serious Adverse Event (SAE)

Time: Day 1 to Day 28

Description: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

Measure: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

Time: Day 1 to Day 28
81 Efficacy of Injectable Methylprednisolone Sodium Succinate in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome Under the New Coronavirus (SARS-CoV2): a Phase IIb, Randomized, Double-blind, Placebo-controlled, Clinical Trial.

This is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 416 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MP (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

NCT04343729
Conditions
  1. SARS-CoV Infection
  2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Drug: Methylprednisolone Sodium Succinate
  2. Drug: Placebo solution
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Mortality rate on day 28, after randomization

Measure: Mortality rate at day 28

Time: on day 28, after randomization

Secondary Outcomes

Description: Proportion of patient that died on days 7, 14 and 28.

Measure: Mortality rate on days 7, 14 and 28

Time: after randomization, up to 28 days.

Description: proportion of patients requiring orotracheal intubation

Measure: Incidence of orotracheal intubation

Time: after randomization, up to 7 days.

Description: Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.

Measure: Change in oxygenation index

Time: after randomization, up to 7 days.
82 Corticosteroids During Covid-19 Viral Pneumonia Related to SARS-Cov-2 Infection

Infection with the SARS-Cov-2 virus, responsible of severe acute respiratory distress syndrome (SARS), is an emerging infectious disease called Covid-19 and declared as pandemic by the World Health Organization on March 11, 2020. This pandemic is responsible of significant mortality. In France, several thousand patients are hospitalized in intensive care units, and their number continues to increase. Mortality during Covid-19 is mainly linked to acute respiratory distress syndrome, which frequency is estimated in France to occur in 6% of infected patients. Comorbidities such as cardiovascular conditions, obesity and diabetes increase susceptibility to severe forms of Covid-19 and associated mortality. Therapeutic management has three components: symptomatic management, including supplementary oxygen therapy and in case of respiratory distress mechanical ventilation; the antiviral approach; and immunomodulation, aiming at reducing inflammation associated with viral infection, which is considered to take part in severe presentations of the disease. During Covid-19 viral pneumonia related to SARS-COv-2, there is a significant release of pro-inflammatory cytokines in the acute phase of viral infection, which could participate in viral pneumonia lesions. In children with less mature immune system than adults, SARS-Cov-2 infection is less severe. The current prevailing assumption is that severe forms of Covid-19 may not only be related to high viral replication, but also to an excessive inflammatory response favoring acute lung injury and stimulating infection. The investigators hypothesize that early control of the excessive inflammatory response may help reducing the risk of acute respiratory distress syndrome. The investigators will evaluate the benefit, safety and tolerability of corticosteroid therapy to reduce the rate of subjects hospitalized for Covid-19 viral pneumonia who experience clinical worsening with a need of high-flow supplemental oxygen supplementation or transfer in intensive care units for respiratory support.

NCT04344288
Conditions
  1. Viral Pneumonia Human Coronavirus
  2. COVID-19
Interventions
  1. Drug: Prednisone
  2. Other: Control group
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask. measured twice at 5-15 min intervalsThe average value of the two measurements will be calculated.

Measure: Number of patients with a theoretical respiratory indication for transfer to intensive care unit evaluated by a SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask.

Time: 7 days

Secondary Outcomes

Description: level1: not hospitalized no limited activities, level 7: death

Measure: disease severity assessed on a 7-level ordinal scale

Time: 7 days

Measure: number of patients with a supplemental oxygen use

Time: 7 days

Description: Reduction of radiological signs on chest imaging

Measure: radiological signs on chest imaging

Time: 7 days

Measure: number of patients transferred to intensive care unit

Time: 21 days

Measure: number of patients requiring invasive ventilation

Time: 21 days

Description: duration on days

Measure: Duration of oxygen therapy

Time: 21 days

Measure: number of adverse events induced by corticosteroid treatment

Time: 21 days

Measure: number of patients with infections other than SARS-CoV-2

Time: 21 days

Measure: number of deaths

Time: 21 days
83 Management by Hyperbaric Oxygen Therapy of Patients With Hypoxaemic Pneumonia With SARS-CoV-2 (COVID-19)

Several patients with hypoxaemic SARS-CoV2 pneumonia were able to benefit from hyperbaric oxygen treatment (HBOT) in China. In a clinical case published in the Chinese journal of hyperbaric medicine, treatment with repeated HBO sessions prevented admission to intensive care unit with mechanical ventilation in a patient aged 69 who presented with signs of respiratory decompensation. HBOT is the most powerful oxygenation modality in the body today. HBOT can dramatically increase the amount of dissolved oxygen in the blood. HBOT not only promotes blood transport but also its tissue delivery. Furthermore, HBOT has specific immunomodulatory properties, both humoral and cellular, making it possible, for example, to reduce the intensity of the inflammatory response and to stimulate antioxidant defenses by repeating sessions. A virucidal capacity of HBOT might also be involved. HBOT is generally regarded as safe with very few adverse events. Following this feedback, it is proposed in the context of crisis management related to SARS-CoV2 to assess the value of HBO treatment of patients with CoV2 pneumonia. Indeed, it seems essential to propose therapeutic strategies to limit the risk of respiratory decompensation requiring admission to intensive care unit for patients with SARS-CoV2 pneumonia.

NCT04344431
Conditions
  1. Covid-19
Interventions
  1. Combination Product: Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device)
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time to normalize the oxygen requirement (oxygeno-dependence), i.e. allowing a pulse oximetry value in ambient air greater than or equal to 92% and / or arterial blood gas with a PaO2 value greater than 60mmHg in ambient air.

Measure: Time to normalize the oxygen requirement (oxygeno-dependence)

Time: 1 month

Secondary Outcomes

Description: Number of days with oxygen need, taking into account the predictors of bad outcome

Measure: Days of hospitalization between the HBO group and the control group.

Time: 1 month

Description: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% between the OHB group and the control group.

Measure: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% values between the HBO group and the control group.

Time: 1 month

Description: Days on invasive mechanical ventilation

Measure: Days on invasive mechanical ventilation

Time: 1 month

Description: Mortality

Measure: Mortality

Time: 1 month

Other Outcomes

Description: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation

Measure: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation

Time: 1 month
84 Microbial Etiology of Ventilator-associated Pneumonia (VAP) in COVID-19 Infected Patients

National multicentric observational retrospective case-control study comparing the relative frequency of the various microorganisms responsible for VAP in patients infected or not by SARS-CoV-2 and their resistance to antibiotics.

NCT04344509
Conditions
  1. Ventilator Associated Pneumonia
Interventions
  1. Other: Bacterial species isolated
MeSH:Pneumonia, Ventilator-Associated Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Prevalence of the microorganisms responsible for VAP among patients infected or not by the SARS-CoV-2

Time: 1 month

Secondary Outcomes

Measure: Prevalence of multi-drug resistant bacteria responsible for VAP among patients infected or not by the SARS-CoV-2

Time: 1 month
85 Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS

The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality. Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival. The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.

NCT04344730
Conditions
  1. Acute Hypoxemic Respiratory Failure
  2. COVID-19
Interventions
  1. Drug: Dexamethasone injection
  2. Drug: placebo
  3. Procedure: conventional oxygen
  4. Procedure: CPAP
  5. Procedure: HFNO
  6. Procedure: mechanical ventilation
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: The time-to-death from all causes within the first 60 days after randomization.

Measure: The time-to-death from all causes

Time: day-60

Description: the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.

Measure: The time to need for mechanical ventilation (MV)

Time: day-28.

Secondary Outcomes

Description: The cycle threshold for SARS-CoV-2 PCR at baseline, day 7 and day 10 in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)

Measure: The viral load in the respiratory tract

Time: day-10

Description: Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28

Measure: Number of patient with at least one episode of healthcare-associated infections

Time: day-28

Description: To compare the exposition to mechanical ventilation

Measure: Number of days alive without mechanical ventilation

Time: day-28

Description: Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)

Measure: Measure of SOFA score

Time: day-28

Description: to compare the exposition to renal replacement therapy

Measure: Number of days alive without renal replacement therapy

Time: day-28

Description: To compare the lengths of ICU

Measure: Lengths of ICU-stay

Time: day-60

Description: To compare the lengths of hospital-stay

Measure: Lengths of hospital-stay

Time: day-60

Description: Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation

Measure: Number of patients with severe hypoxemia,

Time: day 60

Description: Proportion of patients with cardiac arrest within 1 hour after intubation

Measure: Number of patients with cardiac arrest within 1 hour after intubation

Time: day 60
86 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-COAG Trial

COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent Covid-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. This protocol CORIMUNO19-COAG will evaluate the efficacy and safety of active anticoagulation using heparin: Tinzaparin (INNOHEP®) or unfractionated heparin (Calciparine®, Héparine Sodique Choay®) in COVID-19 patients hospitalized in conventional or intensive care units. It will use a phase 2 randomized open-label multicentre clinical trial, where patients will be randomly allocated to anticoagulation versus Standard of Care.

NCT04344756
Conditions
  1. COVID19 Pneumonia
Interventions
  1. Drug: Tinzaparin or unfractionated heparin
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: group 1

Measure: Survival without ventilation (VNI or mechanical ventilation)

Time: day 14

Description: group 2

Measure: ventilator free survival

Time: day 28

Secondary Outcomes

Description: range from 0 (healthy) to 10 (death) values below or equal to 5 correspond to the absence of any oxygen supply beside nasal or facial mask

Measure: World Health Organisation(WHO) progression scale ≤5

Time: day 4

Description: range from 0 (healthy) to 10 (death)

Measure: World Health Organisation(WHO) progression scale

Time: day 4, 7 and 14

Measure: overall survival

Time: day 14, 28 and 90

Measure: Length of hospital stay

Time: day 28

Measure: Length of ICU stay

Time: day 28

Measure: time to oxygenation supply independency

Time: day 28

Measure: time to ventilator (non invasive or invasive)

Time: day 28

Description: according to Acute Kidney Injury (AKIN) classification system

Measure: rate of acute kidney injury

Time: day 28

Measure: time to Renal Replacement Therapy (RRT) initiation

Time: day 28

Description: confirmed by objective testing

Measure: rate of clinically overt pulmonary embolism or proximal deep vein thrombosis

Time: day 14 and day 90

Description: confirmed by objective testing

Measure: Rate of clinically overt arterial thrombosis

Time: day 14 and day 90

Measure: Rate of unscheduled central venous catheter replacement for catheter dysfunction

Time: day 28

Description: as a thrombus extending from the catheter into the lumen of the deep vein where the catheter is inserted diagnosed with radiologic imaging in case of a clinical suspicion of upper/lower limb DVT or pulmonary embolism or compulsory catheter removal

Measure: Rate of central venous catheter-related deep vein thrombosis (CVC-DVT)

Time: day 28

Measure: Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction

Time: day 28

Measure: Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not

Time: day 28

Measure: Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

Time: day 28

Measure: Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

Time: day 28

Measure: Incidence of adverse events

Time: day 28
87 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-19- BEVA Trial

Bevacizumab, ZERIBEV® (Pfizer)/AVASTIN® (Roche) 25 mg/ml ®, is a recombinant humanised monoclonal IgG1 antibody It seems interesting to use bevacizumab in severe patients infected with SARS-CoV-2 requiring hospitalization in conventional unit or in ICU. This protocol CORIMUNO19-BEVA will evaluate the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) COVID-19 patients hospitalized in conventional units. This phase 2 randomized clinical trial aimed at evaluating the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) alone versus standard of care (SoC) in patients hospitalized in conventional units.

NCT04344782
Conditions
  1. COVID19 Pneumonia
Interventions
  1. Drug: Bevacizumab Injection
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Proportion of surviving patients without need for intubation for respiratory support

Time: day 14

Secondary Outcomes

Description: value of a healthy individual occurs between 95 - 100

Measure: Saturation of Oxygen in the blood (SaO2)

Time: day 14

Description: value of a healthy individual occurs between 75-100 mmHg

Measure: Arterial oxygen partial pressure (paO2)

Time: day 14

Description: Normal level should be >500 Index of severity of acute respiratory distress syndrome (ARDS) mild if 200-300 moderate if 100-200 severe if < 200

Measure: Ratio of arterial oxygen partial pressure to fractional inspired oxygen (paO2/FiO2)

Time: day 14

Description: based on a Likert scale with scores ranging from 1 to 5 (1-definitely no; 2-probably no; 3-equivocal; 4-probably yes; 5-definitely yes)

Measure: CT-scan score

Time: day 14

Description: measured on an visual analog scale (VAS), ranging from 0 (no dyspnea) to 10 (major dyspnea)

Measure: dyspnea

Time: day 28

Measure: overall survival

Time: day 14 and 28

Measure: admissionn to the intensive care unit (ICU)

Time: day 14 and day 28

Measure: incidence of mechanical ventilation

Time: day 14 and day 28

Measure: hospital length of stay

Time: day 28

Measure: incidence of adverse event

Time: day 28

Measure: VEGF plasma concentration

Time: day 28
88 Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial

This is an open label clinical study to evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection. The study aims to document possible prevention of pneumonia in patients staying at home and in improving the symptoms of SARS-CoV-2 pneumonia in patients who will be hospitalised.

NCT04344951
Conditions
  1. Pneumonia, Viral
  2. Covid-19
Interventions
  1. Drug: UNIKINON (Chloroquine phosphate) 200mg tablets
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Achieving 50% reduction in symptom score for patients with lower respiratory tract infection on day 8 visit from study initiation.

Measure: 50% reduction in symptom score for patients with lower respiratory tract infection

Time: Day 8 visit from study initiation

Description: Lack of progression to lower respiratory tract infection in patients enrolled in the study due to upper respiratory tract infection on day 8 visit from study initiation.

Measure: Lack of progression for patients with upper respiratory tract infection

Time: Day 8 visit from study initiation

Secondary Outcomes

Description: Lower respiratory tract infection rating takes place. The symptoms checked are: Cough, Chest pain, Dyspnea, expectoration. For each symptom score is given from 0 to 3 depending on the intensity and they are summed.

Measure: Comparison of the primary endpoint with respective patients not receiving the treatment

Time: Day 14 visit from study initiation

Description: It is defined as the presence of both of the following: Respiratory quotient (pO2 / FiO2) less than 150 Need for treatment with CPAP or mechanical ventilation

Measure: Serious respiratory failure until day 14. This will be compared with respective patients not receiving the treatment.

Time: Day 14 visit from study initiation

Description: Frequency of AEs and SAEs

Measure: Frequency of AEs and SAEs

Time: Day 14 visit from study initiation
89 Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial

CCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled trial, which aims to assess the safety and efficacy of treatment with convalescent plasma for patients with moderate-severe COVID-19. Participants will be randomized 2:1 to two parallel treatment arms: Convalescent plasma, and intravenous placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.

NCT04345289
Conditions
  1. COVID
  2. Corona Virus Infection
  3. Viral Pneumonia
Interventions
  1. Biological: Convalescent anti-SARS-CoV-2 plasma
  2. Other: Infusion placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Composite outcome

Measure: All-cause mortality or need of invasive mechanical ventilation

Time: 28 days

Secondary Outcomes

Description: Number of participants with adverse events with possible relation to study drug

Measure: Frequency of adverse events

Time: 90 days

Description: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines

Measure: Frequency of severe adverse events

Time: 90 days

Description: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities

Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status

Time: 90 days

Description: Number of days without mechanical ventilation

Measure: Ventilator-free days

Time: 28 days

Description: Number of days without organ-failure

Measure: Organ failure-free days

Time: 28 days

Description: Number of days in ICU

Measure: Duration of ICU stay

Time: 90 days

Description: Number of deaths by any cause

Measure: Mortality rate

Time: 7, 14, 21, 28 and 90 days

Description: Days from the date of hospital admission for COVID-19 to the date of discharge

Measure: Length of hospital stay

Time: 90 days

Description: Days requiring supplement oxygen

Measure: Duration of supplemental oxygen

Time: 90 days
90 A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia (CARDEA)

Part 1 of this trial enrolled 30 patients to receive Auxora (formerly CM4620) in a 2:1 randomized, open label trial of patients with severe and critical COVID-19 pneumonia. Part 2 will consist of a randomized, double blind, placebo-controlled (RCT) study that will evaluate efficacy, safety, and the pharmacokinetic profile of Auxora in patients with severe COVID-19 pneumonia. Four hundred patients will be randomized 1:1 to receive Auxora or matching placebo. Patients with an estimated PaO2/FiO2 of 75-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. The number of patients with an imputed PaO2/FiO2 >200 randomized into the study will be capped at 80. Subgroup analyses will be performed to explore how time to recovery is influenced by baseline variables and to evaluate the treatment effect at different levels of each of these variables. The dose of Auxora will be 2.0 mg/kg (1.25 mL/kg) administered at 0 hour, and then 1.6 mg/kg (1 mL/kg) at 24 hours and 1.6 mg/kg (1 mL/kg) at 48 hours from the SFISD. The dose of placebo will be 1.25 mL/kg administered at 0 hour and then 1 mL/kg at 24 hours and 1 mL/kg at 48 hours from the SFISD. Remdesivir, corticosteroids and convalescent plasma will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides informed consent.

NCT04345614
Conditions
  1. Pneumonia
Interventions
  1. Drug: Auxora
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Defined as the number of days hospitalized but not requiring supplemental oxygen or ongoing medical care, or; discharged and requiring supplemental oxygen, or; discharged, not requiring supplemental oxygen.

Measure: Number of days from the Start of the First Infusion of Study Drug (SFISD) to recovery

Time: From start of first infusion of study drug to day 30

Secondary Outcomes

Measure: Proportion of patients requiring invasive mechanical ventilation or dying

Time: from start of start of first infusion of study drug and up to day 30

Measure: Proportion of patients requiring invasive mechanical ventilation

Time: from start of start of first infusion of study drug and up to day 30

Description: The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen

Measure: Differences in outcomes as measured by an 8-point ordinal scale

Time: from randomization through Days 12 and 30

Measure: Proportion of patients who have died at day 30 (mortality)

Time: Day 30

Measure: Number of days in the hospital

Time: from admission into the hospital until discharge from the hospital

Measure: Number of days in the Intensive Care Unit (ICU)

Time: from admission into ICU until discharge from ICU

Measure: Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE)

Time: from randomization and through day 30

Description: Concentration measured using a validated assay

Measure: CM4620-IE serum concentration

Time: enrollment through 72 hours
91 Randomized Trial Assessing Efficacy and Safety of Hydroxychloroquine Plus Azithromycin Versus Hydroxychloroquine for Hospitalized Adults With COVID-19 Pneumonia

Double blinded randomized clinical trial designed to evaluate the efficacy and safety of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with confirmed COVID-19 pneumonia.

NCT04345861
Conditions
  1. Coronavirus Infection
  2. Pneumonia, Viral
Interventions
  1. Drug: Hydroxychloroquine + placebo
  2. Drug: hydroxychloroquine + azithromycin
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points (score range from 1 to 7 , with 7 being the worst score)

Measure: Time to clinical improvement of at least 1 level on the ordinal scale between Day 1 (day of the first administration of study drug) to Day 11 (day after last day of treatment).

Time: up to Day 11

Secondary Outcomes

Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points at day 15 and day 29

Measure: Clinical status assessed by ordinal scale

Time: up to Day 29

Description: Necessity for transfer to Intensive care unit

Measure: transfer to ICU

Time: up to Day 29

Description: days from admission to hospital discharge

Measure: Length of hospital day

Time: up to Day 29

Description: incidence of all-cause mortality

Measure: Hospital Mortality

Time: Day 29

Description: Need to mechanical ventilation

Measure: Need to Mechanical Ventilation

Time: up to Day 29

Description: adverse reactions

Measure: Occurence of grade 3-4 adverse event

Time: up to Day 29

Description: ECG

Measure: QTc Lengthening

Time: up to Day 11

Description: Thoracic CT scan : number and size of ground-glass opacifications on day 1 and day 11 Two independent pulmonary imagery experts will assess abnormalities according to a standardized framework

Measure: Evolution of pulmonary CT scan images

Time: up to Day 11
92 Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Baricitinib, Imatinib or Supportive Treatment in Patients With SARS Cov2 Pneumonia

In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak. For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases. The study aims to compare Imatinib 400mg, Baricitinib 4mg or supportive treatment, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment. Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1

NCT04346147
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Imatinib tablets
  2. Drug: Baricitinib Oral Tablet
  3. Other: Supportive tratment
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: time from inclusion to improvement by 2 points on the "seven-category ordinal scale" or high, whichever comes first

Measure: time to clinical improvement

Time: baseline to day 14

Secondary Outcomes

Description: number of serious adverse effects and premature discontinuation of treatment

Measure: Safety of treatments

Time: through study completion, an average of 1 month

Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

Measure: Tolerability of treatments

Time: during treatment and up to 30 days after the last treatment dose

Other Outcomes

Description: Possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 using high-performance techniques with serum DNA from the participants

Measure: Biomarkers and genetic markers of susceptibility to SARS-CoV-2

Time: baseline
93 An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.

NCT04346355
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours

Measure: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation

Time: two weeks from participants' allocation to study arm

Secondary Outcomes

Description: Death

Measure: Death from any cause

Time: Two weeks from participants' allocation to study arm

Description: Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale

Measure: Tocilizumab toxicity

Time: Two weeks from participants' allocation to study arm

Description: Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment

Measure: Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment

Time: Two weeks from participants' allocation to study arm

Description: Changes from baseline of the PaO2 / FiO2 ratio

Measure: Evaluate the progress of the PaO2 / FiO2 ratio

Time: Two weeks from participants' allocation to study arm

Description: Changes from baseline of the lymphocyte count

Measure: Evaluate the trend over time of the lymphocyte count

Time: Two weeks from participants' allocation to study arm
94 A Pilot Study to Explore the Efficacy and Safety of Rescue Theraphy With Antibodies From Convalescent Patients Obtained With Double -Filtration Plasmapheresis (DFPP) and Infused in Critically Ill Ventilated Patients With Coronavirus Disease 2019 (COVID-19)

The 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID 19), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite any attempted treatment.. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Plasma-exchange is expensive and requires large volumes of substitution fluid. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The aforementioned limitations of plasma therapy can be overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP).DFPP is a modality of plasma purification that performs an initial plasma separation from blood, and the subsequent separation of specific molecules, on the basis of their specific molecular weight (cut-off), by using a fractionation filter. The Fractionation Filter 2A20, because of its membrane sieving cut-off, retains larger molecules and returns plasma along with smaller molecules to the circulation, including the major part of the albumin. The selection of the membrane 2A20 is related to the appropriate Sieving Coefficient for IgG that allows to efficiently collect antibodies from patients which are recovered from COVID-19, with negligible fluid losses and limited removal of albumin. The total amount of antibodies obtained during one DFPP session exceeds by three to four times the total amount provided to recipients with one unit of plasma obtained during one plasma-exchange session from one COVID-19 convalescent donor. This should result in more effective viral inhibition and larger benefit for the patient achieved with one unit of enriched immunoglobulin solution obtained with DFPP than with one unit of plasma obtained with plasma exchange. These observations provide the background for a pilot study aimed to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for critically ill patients with severe coronavirus (COVID-19) pneumonia requiring mechanical ventilation.

NCT04346589
Conditions
  1. Pneumonia, Ventilator-Associated
  2. Coronavirus Infection
Interventions
  1. Biological: Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients
MeSH:Pneumonia, Ventilator-Associated Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Number of mechanical ventilation days.

Time: Through study completion, an average of 6 months.

Secondary Outcomes

Measure: Survival

Time: Through study completion, an average of 6 months.

Measure: Shift to Continuous Positive Airway Pressure (CPAP) ventilation

Time: Through study completion, an average of 6 months.

Measure: Referral to a sub-intensive care unit or discharge

Time: Through study completion, an average of 6 months.

Measure: Viral titer

Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

Measure: Anti COVID 19 IgG antibodies

Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

Measure: Anti COVID 19 IgM antibodies

Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

Description: Marker of complement activation in plasma.

Measure: C5a concentration

Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

Description: Marker of complement activation in plasma.

Measure: C3a concentration

Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

Description: Marker of complement activation in plasma.

Measure: Serum C5b-9 concentration

Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
95 An Open Randomized Study of the Effectiveness of the Drug Dalargin for the Prevention and Treatment of Symptoms of Pulmonary Complications in Patients With Coronavirus Infection (SARS-COVID-19)

The purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019 ). Test drug that will be administered to patients are: - Dalargin, solution for inhalation administration, - Dalargin, solution for intravenous and intramuscular administration.

NCT04346693
Conditions
  1. Acute Respiratory Tract Infection
  2. Acute Respiratory Insufficiency
  3. Pneumonia
  4. Septic Shock
  5. Hypoxemia
Interventions
  1. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation.
  2. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection
  3. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation
  4. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation
MeSH:Infection Respiratory Tract Infections Pneumonia Respiratory Insufficiency Pulmonary Valve Insufficiency Hypoxia
HPO:Hypoxemia Pneumonia Pulmonary insufficiency Respiratory tract infection

Primary Outcomes

Description: Estimated by Polymerase chain reaction (PCR)

Measure: The change of viral load in patients with SARS-COVID-19.

Time: Upon patient inclusion in the study, after 96 hours and on the 10day;

Description: Assessed through the entire patient participation in the study

Measure: The frequency of development of Acute Respiratory Distress Syndrome (ADRS)

Time: up to 10 days

Description: The number of days a patient is hospitalized

Measure: Duration of hospitalization

Time: up to 10 days

Description: Early mortality from all causes will be estimated

Measure: The frequency of early mortality

Time: up to 30 days

Description: Late mortality from all causes will be estimated

Measure: The frequency of late mortality

Time: up to 90 days

Description: Clinical status at the time of completion of participation in the study will be estimated based upon the following criteria: Death; Hospitalization is extended, on invasive mechanical ventilation of the lungs with extracorporeal membrane oxygenation; Hospitalization extended, on non-invasive ventilation; Hospitalization is extended, needs additional oxygen; Hospitalization is extended, additional oxygen is not required; Discharged.

Measure: Clinical status at the time of completion of participation in the study

Time: an average of 10 days
96 An Open Randomized Study of the Effectiveness of the Drug Mefloquine, Tablets 250 mg, Produced by FSUE SPC "Farmzashita" of the Federal Medical Biological Agency, FMBA of Russia (Russia) for the Treatment of Patients With COVID19

Study of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" Farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.

NCT04347031
Conditions
  1. Pneumonia, Viral
  2. Respiratory Failure
Interventions
  1. Drug: Mefloquine
  2. Drug: Hydroxychloroquine
  3. Combination Product: Mefloquine + azithromycin + / - tocilizumab
  4. Combination Product: Hydroxychloroquine + azithromycin + / - tocilizumab
MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: The number of patients with development of respiratory failure requiring transfer to the ICU.

Measure: 1st primary endpoint for group 1

Time: up to 10 days

Description: The period of clinical recovery.

Measure: 2nd primary endpoint for group 1

Time: up to 10 days

Description: The period of clinical recovery.

Measure: 1st primary endpoint for group 2

Time: up to 10 days

Description: Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)

Measure: 2nd primary endpoint for group 2

Time: through study completion, an average of 3 months

Secondary Outcomes

Description: A change in viral load by conducting PCR assay through different timeframes

Measure: 1st secondary endpoint for group 1

Time: on days 5 and 10

Description: Frequency of clinical cure on day 10 from the start of therapy

Measure: 2nd secondary endpoint for group 1

Time: on day 10

Description: The retention time of the reaction temperature from the start of the treatment.

Measure: 3d secondary endpoint for group 1

Time: up to 10 days

Description: Concentration of C-reactive protein in blood plasma.

Measure: 4th secondary endpoint for group 1

Time: up to 10 days

Description: Respiratory index.

Measure: 5th secondary endpoint for group 1

Time: up to 10 days

Description: Frequency appearance unwanted phenomena and serious unwanted phenomena

Measure: 6th secondary endpoint for group 1

Time: up to 10 days

Description: A change in viral load by conducting PCR assay through different timeframes

Measure: 1st secondary endpoint for group 2

Time: on days 5 and 10

Description: Respiratory index.

Measure: 2nd secondary endpoint for group 2

Time: up to 10 days

Description: The retention time of the reaction temperature from the start of treatment.

Measure: 3d secondary endpoint for group 2

Time: up to 10 days

Description: Concentration of C-reactive protein in blood plasma.

Measure: 4th secondary endpoint for group 2

Time: up to 10 days

Description: Number of patients required transition to alternative therapy schedule

Measure: 5th secondary endpoint for group 2

Time: up to 10 days

Description: Frequency of adverse events and serious adverse events

Measure: 6th secondary endpoint for group 2

Time: up to 10 days
97 EVALUATION OF THE EFFICACY OF THE HYDROXYCHLOROQUINE-AZITHROMYCIN COMBINATION IN THE IN THE PREVENTION OF COVID-19 RELATED SDRA

Since end of December, a new coronavirus, close to the 2002 SARS coronavirus, cause serious pneumonias throughout world. There is currently no strong evidence of an efficient specific treatment. Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients. This study wants to evaluate the clinical impact of adding Azithromycin to Hydroxychloroquine in the treatment of Sars-CoV-2 pneumonia

NCT04347512
Conditions
  1. Sars-CoV-2, Community-Acquired Pneumonia,COVID-19
Interventions
  1. Drug: Hydroxychloroquine and azithromycin treatment arm.
  2. Drug: Hydroxychloroquine
  3. Drug: Control arm
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A significant hypoxemia is an arterial partial pressure of oxygen of less than 60 mmHg despite an oxygen flow of more than 6 L/min, patient at rest.

Measure: Rate of patients reaching a significant hypoxemia, in each arms.

Time: From day 0 to day 7
98 How COVID-19 Virus Outbreak Affects Antimicrobial Resistance in a Low-middle-income Country's ICU?

A previous study showed a high incidence of ventilator-associated pneumonia to multidrug resistant pathogens in our ICU. That has been related to lack of compliance to hand hygiene among health care providers in ou ICU.

NCT04348227
Conditions
  1. Ventilator Associated Pneumonia
Interventions
  1. Behavioral: Enhanced hygiene measures
MeSH:Pneumonia, Ventilator-Associated Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Incidence of MDR bacteria in endotracheal aspirates

Measure: MDR pathogens in endotracheal aspirates

Time: 1 year

Secondary Outcomes

Description: Incidence of microorganisms in endotracheal aspirates

Measure: Microorganisms in endotracheal aspirates

Time: 1 year
99 Observational Study on the Use of Canakinumab Administered Subcutaneously in the Treatment of Patients With COVID-19 Pneumonia

The study is configured as a retrospective and prospective observational study. The study will be multi-center and will involve all COVID-19 pneumonia patients treated with canakinumab administered subcutaneously.

NCT04348448
Conditions
  1. COVID-19
Interventions
  1. Drug: Canakinumab 150 MG/ML [Ilaris]
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: percentage of patients treated with canakinumab sc who do not require intensive care treatment during hospitalization for COVID-19

Measure: intensive care treatment

Time: 9 months

Secondary Outcomes

Description: ICU stay times

Measure: ICU stay times

Time: 9 months

Description: percentage of patients who died 1 month after treatment

Measure: % died after 1 month after treatment

Time: 9 months

Description: time of hospitalization

Measure: hospitalization

Time: 9 months

Description: number of adverse event

Measure: adverse event

Time: 9 months
100 Open Label Randomized Controlled Trial of Ultraprotective Ventilation Without Extracorporeal Circulation in Patients With COVID 19 Pneumonia and Moderate to Severe ARDS

Mortality of COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) is extremely high in preliminary reports amounting to 50-60%. Duration of mechanical ventilation in these patients appears to exceed standard duration of mechanical ventilation in non-COVID-19 ARDS patients, suggesting that COVID-19 patients may be particularly at risk for ventilator-induced lung injury. Treatment of COVID-19 ARDS patients is to date mainly supportive with protective mechanical ventilation (ventilation with low tidal volume (VT) i.e. 6 ml/kg of predicted body weight (PBW) and plateau pressure control below 30 cm H2O). Mechanical ventilation with VT reduction below 6 ml/kg PBW in ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury. Investigators recently performed a multicenter pilot study on 34 moderately severe to severe ARDS patients. This study demonstrated that ultraprotective ventilation with ultra-low VT (≤4.2 ml/kg PBW) without extracorporeal circulation may be applied in approximately 2/3 of the patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients. Investigators hypothesized that ultraprotective ventilation without extracorporeal circulation may reduce the mortality at day-90 and increase the number of days free from mechanical ventilation (VFD) at day-60, as compared to protective ventilation.

NCT04349618
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID19
  3. Sars-CoV2
  4. Pneumonia
Interventions
  1. Other: PROTECTIVE VENTILATION
  2. Other: ULTRAPROTECTIVE VENTILATION
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
HPO:Pneumonia

Primary Outcomes

Description: For an alive patient at day 90, the score will be built as follow: a value +1 will be given for comparisons to dead patients and alive patients with a lower number of VFD. For comparisons to alive patients with a higher number of VFD a value -1 will be given and in case of identical number of VFD a value 0 will be given. For a dead patient a value -1 will be given for comparisons to alive patients and 0 for comparisons to dead patients. For a given patients the score will correspond to the sum of values resulting to the comparison to all patients of the other group. A higher score indicates a more favorable result.

Measure: A composite score based on all-cause mortality and the number of ventilator free-days (VFD)

Time: Day 90

Secondary Outcomes

Description: All-cause mortality with analysis in intention to treat, i.e. each patient will be analyzed in his initial randomization group regardless of whether the allocated strategy was effectively applied or not.

Measure: All-cause mortality (intention to treat)

Time: 90-day after inclusion

Description: VFD will be computed as follows from the day of inclusion: VFD= 0 if the patient dies between inclusion and day 60 VFD = 60-x if the patient is successfully weaned from invasive mechanical ventilation x days after inclusion. Successful weaning from mechanical ventilation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) VFD= 0 if the patient is mechanically ventilated for more than 60 days after inclusion

Measure: Ventilator-free days (VFD)

Time: day 60 after inclusion

Description: Per protocol analysis will be carried out by comparing the group of patients in whom median daily tidal volume from inclusion to weaning of deep sedation will be lower of equal to 4.2 ml/kg of predicted body weight to the group of patients in whom median tidal volume from inclusion to weaning of deep sedation will be greater than 4.2 ml/kg of predicted body weight, whatever the patients' initial randomization group. Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.

Measure: All-cause mortality with per protocol analysis

Time: 90-day

Description: Successful extubation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) Data will be right censored at 60 days and death will be taken into account as a competing risk.

Measure: Time to successful extubation

Time: 60 days

Description: Data will be right censored at 90 days and death will be taken into account as a competing risk.

Measure: Length of hospital stay

Time: 90 days

Description: Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.

Measure: Respiratory parameters assessed daily from inclusion to weaning of deep sedation or 14 days whichever comes first

Time: 14 days

Description: Doses of the following drugs used for deep sedation will be assessed daily: midazolam, propofol and opioid. Opioid dose will be expressed as morphine equivalent with the following conversion factor: 1µg of sufentanil = 10 µg of fentanyl = 1 mg of morphine

Measure: Daily sedation dose during the first 14 days of the study

Time: 14 days

Description: Rescue therapies are any therapy among the following ones: neuromuscular blocking agents, prone position, nitric oxide, recruitment maneuvers, ECMO

Measure: Rate of use of rescue therapies

Time: 14 days

Description: Severe mixed acidosis is defined by the association of pH<7.15 and PaCO2>45 mm Hg.

Measure: Incidence density rate of severe mixed acidosis

Time: ICU stay

Description: Ventilator associated pneumonia will be defined as any pneumonia acquired under mechanical ventilation after inclusion.

Measure: Incidence density rate of ventilator associated pneumonia

Time: ICU stay

Description: Acute cor pulmonale is defined by the association of right ventricle dilatation (right ventricle surface / left ventricle surface >0,6) and septal dyskinesia assessed by echocardiography

Measure: Incidence density rate of acute cor pulmonale

Time: ICU stay

Description: Barotrauma is defined by any pneumothorax OR pneumomediastinum OR subcutaneous emphysema, OR pneumatocele of more than 2 cm detected on image examinations.

Measure: Incidence density rate of barotrauma

Time: ICU stay

Description: Serious adverse event is any life threatening event OR any event resulting in death.

Measure: Incidence density rate of any serious adverse events

Time: ICU stay

Description: The Telephone Montreal Cognitive Assessment score will be assessed by phone call. The total score ranges from 0 to 30; higher scores being associated to a better outcome.

Measure: Cognitive impairment assessed by phone call using the Telephone Montreal Cognitive Assessment (T-MoCA) test

Time: Day 365 after inclusion

Description: The RAND 36-Item Health Survey (SF-36) score will be assessed by phone call. The score ranges from 0 to 100; higher scores being associated to a better outcome.

Measure: Quality of life assessed by the RAND 36-Item Health Survey (SF-36) score

Time: Day 365 after inclusion

Description: The Impact of Event Scale - revised (IES-R) score will be assessed by phone call. The total score ranges from 0 to 88; higher scores being associated to a worse outcome.

Measure: Post-traumatic stress disorder assessed by the Impact of Event Scale - revised (IES-R) score by phone call

Time: Day 365 after inclusion

Description: The cost-efficacy ratio will be computed as the ratio of cost difference on efficacy difference between the intervention arm and the reference arm. The costs taken into account will be the direct hospitalized costs. The efficacy will be assessed as the number of days alive free from mechanical ventilation.

Measure: Cost-efficacy ratio of the innovative strategy compared to the reference strategy

Time: Day 90 after inclusion
101 A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia

The primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care can alleviate the immune-mediated cytokine release syndrome (CRS) and reduce the time to recovery in hospitalized subjects with severe or critical COVID-19 pneumonia.

NCT04351152
Conditions
  1. Coronavirus Disease 2019 (COVID-19) Pneumonia
Interventions
  1. Biological: Lenzilumab
  2. Drug: Standard of Care
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time to recovery is defined as the first day on which a subject satisfies one of the following 3 categories from the 8-point ordinal scale (Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities).

Measure: Time to Recovery

Time: Up to 28 days

Secondary Outcomes

Measure: Incidence of Invasive Mechanical Ventilation and/or Death

Time: Up to 28 days

Measure: Incidence of severe acute respiratory distress syndrome (ARDS)

Time: Up to 28 days

Measure: Duration of Intensive Care Unit (ICU) Stay

Time: Up to 28 days

Measure: Ventilator-free Days

Time: Up to 60 days

Measure: Duration of Hospitalization

Time: Up to 28 days

Measure: Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale

Time: Up to Day 28

Measure: Time to Death

Time: Up to Day 28

Measure: Number of Subjects Alive and Off Oxygen

Time: Up to 60 days

Description: Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Measure: Percentage of Participants Experiencing Adverse Events

Time: Up to 60 days

Description: Using the NCI CTCAE version 5.0

Measure: Percentage of Participants Experiencing Serious Adverse Events

Time: Up to 60 days

Measure: Proportion of Subjects Discharged from Hospital

Time: Up to Day 60

Measure: All-cause Mortality and Proportion of Subjects Alive

Time: Day 28 and Day 60

Measure: Time to improvement in oxygenation for > 48 hours

Time: Up to Day 28

Measure: Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)

Time: Up to Day 28

Description: NEWS2 consists of: Physiological Parameters: respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), use of air or oxygen, systolic blood pressure (mmHg), pulse (per minute), consciousness and temperature (°C)

Measure: Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours

Time: Up to Day 28

Measure: Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale

Time: Up to Day 28

Measure: Duration of Time on Low-flow or High-flow Supplemental Oxygen

Time: Up to Day 28
102 IV Infusion of Autologous Adipose Derived Mesenchymal Cells for Abatement of Respiratory Compromise in SARS-CoV-2 Pandemic (COVID-19)

The aim of this study is to evaluate the safety and efficacy of autologous adipose-derived mesenchymal cells for treating confirmed or suspected patients with SARS-CoV-2 and compromised respiratory function requiring hospitalization. The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV to eligible patients will improve clinical outcomes of COVID 19 positive patients with severe pneumonia or ARDS by reducing or avoiding cytokine storm.

NCT04352803
Conditions
  1. Covid-19 Pneumonia
  2. Cyotokine Storm
Interventions
  1. Biological: Autologous Adipose MSC's
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Incidence of unexpected adverse events within 28 days following IV administration of MSCs.

Measure: Safety - Incidence of unexpected adverse events

Time: up to 28 days

Description: Changes in progression or rate of subjects progressing to mechanical ventilation

Measure: Efficacy - Frequency of progression to mechanical ventilation

Time: up to 28 days

Description: Changes in time subjects remain on mechanical ventilation

Measure: Efficacy - Changes in length of mechanical ventilation

Time: up to 28 days

Description: Changes in length of time subjects wean off of mechanical ventilation

Measure: Efficacy - Changes in length of weaning of mechanical ventilation

Time: up to 28 days

Description: Length of Hospital Stay

Measure: Efficacy - Changes in length of hospital stay

Time: up to 28 days

Description: Mortality rate from all causes

Measure: Efficacy - Changes in mortality rate

Time: up to 28 days
103 A Prospective International Lung UltraSound Analysis (ILUSA) Study in Tertiary Maternity Wards During the SARS-CoV-2 Pandemic

Currently there is a great need for an accurately and rapid assessment of patients suspected for Covid-19. Like CT, Lung Ultrasound (LUS) examination can potentially help with the initial triage of patients but also help track the evolution of the disease. LUS can be used in every setting, including settings with limited infrastructure, allowing the reduction of disparities in trials participation. LUS is also a practical approach that can be used by obstetricians/gynecologists, who are the primary care givers in the labour and delivery room. The International Lung UltraSound Analysis (ILUSA) Study is an international multicenter prospective explorative observational study to assess the predictive value of LUS in Covid-19 suspected and diagnosed pregnant patients.

NCT04353141
Conditions
  1. COVID
  2. Pregnancy Complications, Infectious
  3. Pregnancy Related
  4. Pregnancy, High Risk
  5. Pregnancy Disease
  6. Pneumonia
  7. Pneumonia, Viral
  8. Diagnoses Disease
Interventions
  1. Diagnostic Test: standardized Lung Ultrasound (LUS) examination
MeSH:Pregnancy Complications, Infectious Pneumonia, Viral Pneumonia Pregnancy Complications
HPO:Pneumonia

Primary Outcomes

Description: The primary endpoint is diagnostic performance in terms of the area under the receiver operating characteristic curve (AUC, also known as the c-statistic) and sensitivity and specificity with regard to the prediction of poor outcome. Outcome at one week from admission: good outcome includes discharge or inpatient breathing in free air; poor outcome includes patient with oxygen support, patients with CPAP/ high oxygen flow cannula, or patient with endotracheal intubation during the week.

Measure: Diagnostic performance of LUS to predict poor outcome

Time: outcome one week after enrollment into the study
104 Study of Biomarkers in the Long-term Impact of Coronavirus Infection in the Cardiorespiratory System: Effect of Hydroxychloroquine / Azithromycin Combined Therapy

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.

NCT04353245
Conditions
  1. COVID19
  2. Corona Virus Infection
  3. Myocardial Injury
  4. Pneumonia
Interventions
  1. Other: BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM
MeSH:Infection Communicable Diseases Coronavirus Infections Virus Diseases Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry

Measure: Fibrosis

Time: 12 months

Description: Decreased functional capacity on ergospirometers

Measure: Ergospirometers

Time: 12 monthes
105 Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia

In the current situation it is of great importance to discover a safe, cost-effective and available treatment strategy in order to limit the rapidly spreading SARS-Cov-2. Recent studies have shown that hydroxychloroquine could have a role in the treatment of infected patients. It is however not very likely that hydroxychloroquine alone could be adequate for treatment of Covid-19 disease. Effective therapy that prevents the virus entrance should contain at least TMPRSS2 inhibitor or a competitive inhibitor of viral ACE 2 binding. The use of bromhexine at the dose adequate to selectively inhibit the TMPRSS2, resulting in preventing of viral entrance via TMPRSS2-specific pathway, coud be an effective treatment of Covid-19. In our study we would like to explore the therapeutic potential of bromhexin and hydroxychloroquine in Covid-19 patients. Hypothesis 1. Combined treatment with bromhexin and hydroxychloroquine shortens the course of disease in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 2. Combined treatment with bromhexin and hydroxychloroquine lowers the incidence of secundary pulmonary infections in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 3. Combined treatment with bromhexin and hydroxychloroquine decreases the need for ICU admission in hospitalized Covid-19 patients compared to hydroxychloroquine alone.

NCT04355026
Conditions
  1. Covid-19
Interventions
  1. Drug: Bromhexine Oral Tablet and/or hydroxychloroquine tablet
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: number of days the patient is treated in the hospital

Measure: Duration of hospitalization

Time: through study completion, an average of 6 months

Description: Number of days from the onset of symptoms to hospital discharge

Measure: Duration of disease

Time: through study completion, an average of 6 months

Secondary Outcomes

Description: Incidence of HAP

Measure: Hospital-aquired pneumonia

Time: through study completion, an average of 6 months

Description: Number of days spent in the ICU

Measure: ICU stay duration

Time: through study completion, an average of 6 months

Description: number of days on oxygene therapy

Measure: Oxygene therapy duration

Time: through study completion, an average of 6 months

Description: Number of hours on mechanical ventilation

Measure: Mechanical ventilatory support duration

Time: through study completion, an average of 6 months
106 Efficacy of Captopril Nebulization in Covid-19 Patients Suffering of SARS CoV-2 Pneumonia. A Randomized Phase II Study

Captopril being an effective drug available in liquid preparation, administration by nebulization could be of interest for maximizing lung action and minimizing systemic side effects. Such a treatment might be used for "Covid-19" patients with pneumonia in order to avoid ARDS.

NCT04355429
Conditions
  1. Pneumonia
  2. Coronavirus Infection
  3. COVID-19
Interventions
  1. Drug: captopril 25mg
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To assess determine the efficacy of captopril nebulization addition to standard of care compared to standard of care in term of 14-day ventilation free survival

Measure: Efficacy of captopril nebulization addition to standard of care compared to standard of care.

Time: 14 Days
107 SOLIRIS® (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID 19) - An Expanded Access Program for Hospital-based Emergency Treatment

This protocol provides access to eculizumab treatment for participants with severe COVID-19.

NCT04355494
Conditions
  1. COVID-19
  2. Pneumonia, Viral
  3. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Interventions
  1. Biological: eculizumab
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

108 Treatment With Inhaled Corticosteroids in Patients Hospitalized Because of COVID19 Pneumonia

Randomized, prospective, controlled open label clinical trial aimed at investigating if the addition of inhaled corticosteroids (budesonide) reduces treatment failure (defined as a composite variable by the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) according to hospital standard of care guidance) at day 15 after initiation of therapeutic intervention.

NCT04355637
Conditions
  1. Coronavirus Infection
Interventions
  1. Drug: Inhaled budesonide
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: composite variable that includes the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) at day 15 after initiation of therapeutic intervention

Measure: Proportion of patients in both arms fulfilling the criteria for treatment failure

Time: 15 days after treatment

Secondary Outcomes

Description: Yes/no

Measure: ICU admission

Time: baseline, day 3, day 7, day 15, day 30

Description: yes/no and reason

Measure: ICU refusal

Time: baseline, day3, day 7, day 15, day 30

Description: infectious cardiovascular and /or metabolic complications as well as variation in the 7 point WHO scale.

Measure: Occurrence of complications

Time: baseline, day3, day 7, day 15, day 30

Description: U/L

Measure: lactate dehydrogenase (LDH)

Time: at baseline, day 3, day 7, day 15, day 30

Description: mg/dL

Measure: C Reactive Protein (CRP)

Time: at baseline, day 3, day 7, day 15, day 30

Description: ng/mL

Measure: ferritin

Time: at baseline, day 3, day 7, day 15, day 30

Description: ng/mL

Measure: D-dimer

Time: at baseline, day 3, day 7, day 15, day 30

Description: x10^9/L

Measure: leukocyte counts

Time: at baseline, day 3, day 7, day 15, day 30
109 Non-Invasive Monitoring of Respiratory Function in Spontaneously Breathing Patients With COVID-19 Infection

This study uses the AirGo band to monitor changes in tidal ventilation in spontaneously breathing patients with COVID-19 associated respiratory failure. It aims to recognize patterns of ventilation associated with worsening respiratory failure in this patient population. If successful, this study will lead to the development of new robust methods for real-time, continuous monitoring of respiratory function in patients with respiratory failure. In turn, such monitoring methods may enable improvements in the medical management of respiratory failure and timing of interventions.

NCT04356443
Conditions
  1. Respiratory Failure
  2. Ventil
  3. Ventilatory Failure
  4. COVID-19
  5. Pneumonia
  6. ARDS, Human
Interventions
  1. Device: AirGo Respiratory Monitor
MeSH:Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Hypoventilation
HPO:Hypoventilation Pneumonia

Primary Outcomes

Description: Progression of respiratory failure to require endotracheal intubation (and mechanical ventilation)

Measure: Endotracheal intubation during present hospitalization, recorded through chart review

Time: Up to three weeks

Secondary Outcomes

Description: Maintenance of SpO2 >=90% on no or low flow supplemental oxygen (=< 1 liter by nasal cannula or CPAP, or return of supplemental oxygen to baseline if required supplemental O2 for another indication, prior to onset of COVID-19 infection)

Measure: Improvement in hypoxemia as indicated by oxygen saturation and requirement for supplemental oxygen, recorded through chart review

Time: Up to three weeks

Description: Patient or care provider may request removal of the band for any reason prior to the patient reaching the outcome

Measure: Premature need for removal of the band, recorded through investigator report

Time: Up to three weeks

Description: Death from any cause while in the hospital

Measure: In-hospital mortality, recorded through chart review

Time: Up to 24 weeks
110 COVID-19: A Pilot Study of Adaptive Immunity and Anti-PD1

This is an open-label, controlled, single-centre pilot study of nivolumab in adult patients with COVID-19. This clinical study aims to evaluate efficacy of anti-PD1 antibody in relation to viral clearance and its safety.

NCT04356508
Conditions
  1. COVID-19
  2. SARS-CoV-2
  3. 2019-nCoV
  4. Pneumonia, Viral
Interventions
  1. Drug: Nivolumab
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Viral load changes in NPS based on SARS-CoV-2 RT-PCR

Measure: Viral clearance kinetics

Time: From diagnosis to recovery, assessed up to 6 months

Secondary Outcomes

Description: Incidence and severity of treatment-related adverse events

Measure: Treatment-related adverse events of nivolumab (Intervention arm only)

Time: Up to 1 year after nivolumab dosing

Description: Changes in lymphocyte counts

Measure: Lymphocyte kinetics

Time: On days 1, 4, 6, 8, 10 and 28 from study enrollment

Description: Changes in cytokine levels (e.g. IL-1B, IL-2, IL-6, TNFa)

Measure: Cytokine kinetics

Time: On days 1, 4, 6, 8 and 10 from study enrollment

Measure: Length of inpatient stay due to COVID-19

Time: From hospital admission to discharge, assessed up to 6 months
111 Efficacy of Pulmonary Physiotherapy on Hospitalized Patients With Novel Coronavirus 2019 Pneumonia

The aim of this study is to evaluate the efficacy of pulmonary physiotherapy on respiratory functions in hospitalized patients with Novel Coronavirus 2019 pneumonia. Patients will be randomized into 1) intervention group: receiving pulmonary physiotherapy technique to improve pulmonary function and walking training or 2) control group: Usual medical care. Patients in both groups will receive therapeutic incentive spirometer. Various outcome measurements of pulmonary functions will be evaluated before and after of interventions. Mortality rate, hospitalization duration and re-admission will be followed until one month after end of intervention. Also, patient's quality of life will be measured after one month.

NCT04357340
Conditions
  1. Covid-19
  2. Pneumonia
  3. SARS Pneumonia
Interventions
  1. Other: Pulmonary Physiotherapy Techniques
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Partial pressure of oxygen in mixed venous blood.

Measure: Mixed venous O2 pressure (PVO2)

Time: Baseline

Description: Partial pressure of oxygen in mixed venous blood.

Measure: Mixed venous O2 pressure (PVO2)

Time: Day 3

Description: Partial pressure of carbon dioxide in mixed venous blood.

Measure: Mixed venous CO2 pressure (PVCO2)

Time: Baseline

Description: Partial pressure of carbon dioxide in mixed venous blood.

Measure: Mixed venous CO2 pressure (PVCO2)

Time: Day 3

Description: Measure of the venous blood acidity or alkalinity

Measure: PH

Time: Baseline

Description: Measure of the venous blood acidity or alkalinity

Measure: PH

Time: Day 3

Description: The amount of bicarbonate ion in the venous blood

Measure: HCO3

Time: Baseline

Description: The amount of bicarbonate ion in the venous blood

Measure: HCO3

Time: Day 3

Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood

Measure: Oxygen saturation (O2 Sat) from VBG

Time: Baseline

Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood

Measure: Oxygen saturation (O2 Sat) from VBG

Time: Day 3

Description: The distance a patient can walk during three minute

Measure: Three minute walk test

Time: Baseline

Description: The distance a patient can walk during three minute

Measure: Three minute walk test

Time: Day 3

Measure: O2 Sat after one minute walking

Time: Baseline

Measure: O2 Sat after one minute walking

Time: Day 3

Measure: O2 Sat after two minutes use of Partial Rebreather

Time: Baseline

Measure: O2 Sat after two minutes use of Partial Rebreather

Time: Day 3

Measure: O2 Sat after two minutes free air breathing

Time: Baseline

Measure: O2 Sat after two minutes free air breathing

Time: Day 3

Measure: O2 sat/ Fio2

Time: Baseline

Measure: O2 sat/ Fio2

Time: Day 3

Secondary Outcomes

Description: The number of dead subjects compared to total patients

Measure: Mortality rate

Time: until one month

Description: Patients' hospitalization after discharge due to any reason

Measure: Number of participants with Rehospitalization

Time: until one moth

Description: Using Short-form 36 questionnaire. The minimum score is 0 and the maximum score is 100. Higher scores mean patient's better quality of life.

Measure: The Health-Related Quality of Life (HRQOL)

Time: One month after end of intervention

Description: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.

Measure: breathlessness

Time: Baseline

Description: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.

Measure: breathlessness

Time: Day 3
112 Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium

The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

NCT04357457
Conditions
  1. Covid 19
  2. Hypoxemic Respiratory Failure
Interventions
  1. Drug: Almitrine
  2. Drug: Placebo
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

Measure: Rate of endotracheal intubation

Time: 7 days

Secondary Outcomes

Measure: 28-day mortality

Time: 28 days

Measure: In-hospital mortality

Time: 28-day

Measure: Number of ventilator-free days

Time: 28 days

Measure: Number of days in the ICU

Time: 28 days

Measure: Number of days in the hospital

Time: 28 days

Description: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.

Measure: Discontinuation rate of the treatment

Time: 28 days
113 COVID-19 Epidemic Response Study: A National Observational Longitudinal Non-Interventional Protocol

A national, observational, longitudinal, non-interventional program aiming to identify prognostic parameters, to investigate the kinetics of the immune response, and to identify predictive biomarkers in SARS-CoV-2 infected patients.

NCT04357496
Conditions
  1. Fever
  2. Pneumonia
  3. Cough
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Blood samples drawn from the infected participants will be analysed for prognostic parameters.

Measure: Identification of prognostic parameters for SARS-CoV-2 infected participants.

Time: 7 months

Secondary Outcomes

Description: Systems from Abbott and Euroimmun will be used for IgG and IgM in SARS-CoV-2.

Measure: Investigation of the kinetics of immune activation and antibody production against SARS-CoV-2 and correlation with clinical course

Time: 7 months

Other Outcomes

Description: Genomic, proteomic, and transcriptomic analyses will be performed on the blood samples drawn from Covid-19 infected participants over the course of 6 months.

Measure: Identification of predictive biomarker/s for clinical course in mildly and severely affected Covid-19 patients using genomic, proteomic, and transcriptomic approach.

Time: 7 months
114 A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia

Study Objectives: Primary - To assess the efficacy (survival without organ failure on Day 14) of three doses of rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or 6 on the World Health Organization (WHO) 9-point severity scale - To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale Secondary - To further assess the efficacy of IV administered rhu-pGSN - To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN - To evaluate the effect of administered rhu-pGSN on survival rates - To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes - [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN Immunogenicity • To investigate the development of antibodies against rhu-pGSN post-treatment

NCT04358406
Conditions
  1. Sars-CoV2
Interventions
  1. Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

Measure: Efficacy: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

Time: Day 14

Description: Proportion of subjects with SAEs as judged by the investigator

Measure: Safety and Tolerability: Proportion of subjects with serious adverse events (SAEs)

Time: Continuous through Day 28

Secondary Outcomes

Description: Daily change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection

Measure: Efficacy: Daily change in the WHO 9-point severity score

Time: Daily through at least Day 14

Description: All cause mortality rate using Kaplan-Meier survival analysis

Measure: Efficacy: All cause mortality rate at Days 28 and 90

Time: At Days 28 and 90

Description: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit, new ongoing need for dialysis/renal replacement therapy

Measure: Efficacy: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy

Time: Days 7, 28, 60, and 90

Description: Proportion of subjects discharged to home or immediate prior residence

Measure: Efficacy: Proportion of subjects discharged to home or immediate prior residence

Time: Continuous through Day 28

Description: LOS of surviving subjects in the hospital and in ICU

Measure: Efficacy: Length of stay (LOS) of surviving subjects in the hospital and in ICU

Time: Continuous through day 28

Description: Proportion of subjects readmitted to the hospital

Measure: Efficacy: Proportion of subjects readmitted to the hospital

Time: Up to 90 days

Description: Proportion of subjects with adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Measure: Safety and Tolerability: Proportion of subjects with adverse events (AEs)

Time: Continuous through Day 28

Description: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

Measure: Safety and Tolerability: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

Time: Continuous through Day 28

Description: Proportion of subjects with rhu-pGSN antibodies

Measure: Immunogenicity: Proportion of subjects with rhu-pGSN antibodies

Time: Days 1, 28, and 90

Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

Measure: Pharmacokinetics: Maximum concentration (C max) of added rhu-pGSN

Time: Continuous through day 3

Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

Measure: Pharmacokinetics: Time to maximum concentration (T max) of added rhu-pGSN

Time: Continuous through day 3

Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

Measure: Pharmacokinetics: Half-life (T 1/2) of added rhu-pGSN

Time: Continuous through day 3

Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

Measure: Pharmacokinetics: Area under the curve from time 0 to 8 hours (AUC 0-8) of added rhu-pGSN

Time: Continuous through day 3

Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

Measure: Pharmacokinetics: Area under the curve from time 0 to infinity (AUC 0-inf) of added rhu-pGSN

Time: Continuous through day 3
115 Mortality Prediction Model for the Triage of COVID-19, Pneumonia and Mechanically Ventilated ICU Patients

The objective of this study is to develop and evaluate an algorithm which accurately predicts mortality in COVID-19, pneumonia and mechanically ventilated ICU patients.

NCT04358510
Conditions
  1. COVID-19
  2. Pneumonia
  3. Mechanical Ventilation
Interventions
  1. Device: COViage
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Deceased or not deceased

Measure: Mortality outcome in COVID-19 ICU patients

Time: Through study completion, an average of 2 months

Description: Deceased or not deceased

Measure: Mortality outcome in mechanically ventilated ICU patients

Time: Through study completion, an average of 2 months

Description: Deceased or not deceased

Measure: Mortality outcome in pneumonia ICU patients

Time: Through study completion, an average of 2 months
116 Expanded Access: Pulsed, Inhaled Nitric Oxide (iNO) for the Treatment of Patients With Mild or Moderate Coronavirus Disease (COVID-19)

The search for novel therapies to address the ongoing coronavirus (COVID-19) pandemic is ongoing. No proven therapies have been identified to prevent progression of the virus. Preliminary data suggest that inhaled nitric oxide (iNO) could have benefit in preventing viral progression and reducing reliance on supplemental oxygen and ventilator support. Expanded access allows for iNO to be delivered via the portable INOpulse delivery system for the treatment of COVID-19.

NCT04358588
Conditions
  1. Coronavirus Infection
  2. COVID-19
  3. Pneumonia, Viral
Interventions
  1. Drug: iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

117 Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact

Retrospective study on the efficacy of baricitinib in 12 COVID-19 patients with moderate pneumonia.

NCT04358614
Conditions
  1. COVID
  2. Pneumonia
Interventions
  1. Drug: Baricitinib 4 MG Oral Tablet
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: All adverse event recording

Measure: To assess the safety of baricitinib combined with antiviral (lopinavir-ritonavir) in terms of serious or non-serious adverse events incidence rate.

Time: 2 weeks

Secondary Outcomes

Description: The percentage of patients improving the clinical and respiratory parameters compared with controls.

Measure: To evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters.

Time: 2 weeks

Description: The percentage of ICU admission in baricitinib group as compared with controls.

Measure: ICU admission rate

Time: 2 weeks

Description: The percentage of discharged in baricitinib group as compared with controls.

Measure: Discharge rate.

Time: 2 weeks
118 Anxiety and Work Resilience Among Tertiary University Hospital Workers During the COVID-19 Outbreak: An Online Survey

For limiting COVID-19 spreading, the World Health Organisation (WHO) recommended worldwide confinement on 2010. In France, unessential institutions were closed on March 14th and population confinement was decided on March 17th. Quarantine and/or confinement could lead to psychological effects such as confusion, suicide ideation, post-traumatic stress symptoms or anger COVID-19 outbreak highlighted a considerable proportion of health care workers (HCW) with depression, insomnia, anxiety and distress symptoms. In front line, facing the virus with the fear of contracting it and contaminate their closest. During previous outbreaks (H1N1, SARS), HCWs have been shown to experience such negative psychological effects of confinement as well as work avoidance behaviour and physical interaction reduction with infected patients (4-7). In France, Covid 19 outbeak led to increase ICU bed capacity with a full reorganization of the human resources. Some caregivers were reassigned to newly setup units admitting or not Covid-19 patients. In the same time, non-caregivers were also encouraged to work at home whenever possible. Thus, every hospital staff member's private and professional life could be altered by the Covid-19 outbreak. As all these changes in the daily life could induce psychological disturbances, the present study was aimed at assessing the acute anxiety level (main objective) of the staff in our Tertiary University Hospital, (6300 employees). Secondarily, the self-reported insomnia, pain, catastrophism and work avoidance behaviour levels were assessed

NCT04358640
Conditions
  1. Critical Illness
  2. Sars-CoV2
  3. SARS Pneumonia
  4. Coronavirus Infection
  5. Stress Disorders, Post-Traumatic
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Critical Illness Stress Disorders, Post-Traumatic
HPO:Pneumonia

Primary Outcomes

Description: Mesured by STAY Scale

Measure: Anxiety

Time: 15 to 45 days after the beginning of the outbreak

Secondary Outcomes

Description: Participant suffering of Insomnia

Measure: Insomnia

Time: 15 to 45 days after the beginning of the outbreak

Description: Participant suffering of catastrophism

Measure: Catastrophism

Time: 15 to 45 days after the beginning of the outbreak
119 Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Plasma From Patients Cured of COVID-19 Compared to the Best Available Therapy in Subjects With SARS-CoV-2 Pneumonia

In early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.

NCT04358783
Conditions
  1. Coronavirus Infection
Interventions
  1. Biological: Plasma
  2. Other: Best Available Therapy
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: any cause mortality during the first 14 days of treatment

Measure: Early all-cause mortality

Time: 14 days

Secondary Outcomes

Description: (48-hour sampling interval from day 3 of hospitalization to two consecutive negatives).

Measure: Time in days for SARS-CoV-2 RT-PCR negatives

Time: 90 days

Description: In subjects of both arms at day 0, 3, 7, 14 and 90.

Measure: The serum anti-SARS-CoV-2 antibody titres

Time: 90 days

Description: Comparison of anti-SARS-CoV-2 antibody titers

Measure: Detection of serum antibodies

Time: days 0, 3, 7, 14 and 90.
120 Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia in Grand Ouest Interregion France

To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD). We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.

NCT04359511
Conditions
  1. COVID-19
Interventions
  1. Drug: Prednisone
  2. Drug: Hydrocortisone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The 7-category ordinal scale is as follow: Not hospitalized with resumption of usual activities Not hospitalized, but unable to resume usual activities Hospitalized, not requiring O2 Hospitalized, requiring O2 from 1 to 5 l/min Hospitalized, requiring O2 >6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death.

Measure: Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.

Time: 14 days

Secondary Outcomes

Measure: Proportion of patients free of oxygen at day 14 and 28

Time: 14 and 28 days

Measure: Proportion of patients discharged alive from hospital at day 14 and 28

Time: 14 and 28 days

Measure: Time to discharge for patients alive

Time: 28 days

Measure: Proportion of patients that were hospitalized to ICU or who died at day 14 and 28

Time: 14 and 28 days

Measure: 14 and 28 day mortality rate

Time: 14 and 28 days

Measure: The time until weaning from oxygen therapy

Time: 28 days

Measure: The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28

Time: 14 and 28 days
121 Prognostic Value of Serum Interleukin-6 (IL-6) and Soluble Interleukin-6 Receptor (sIL-6R) in Severe Coronavirus Disease (COVID-19) Pneumonia Treated With Tocilizumab - a Prospective Single Center Study (UHID-COVID19)

This is a single arm, prospective, observational, single center study to assess the role of interleukin-6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) as predictors of efficacy and safety outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab. At least 30 patients will be enrolled who are diagnosed with severe COVID-19 pneumonia and meet the entry criteria.

NCT04359667
Conditions
  1. COVID-19
  2. Severe Pneumonia
Interventions
  1. Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

Time: baseline

Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

Time: 24 hours post treatment

Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

Time: 48 hours post treatment

Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

Time: on Day 7

Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

Time: on Day 28
122 Bacterial and Fungal Microbiota of Patients With Severe Viral Pneumonia With SARS-CoV2

Observational pilot single-center study aiming to determine the microbiota of critically ill patients infected with SARS-CoV-2. COVID-19 patients will be compared to historical critically ill controls with no SARS-CoV-2 infection.

NCT04359706
Conditions
  1. Sars-CoV2
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: relative abundances and diversity indices

Measure: Composition of the fecal bacterial and fungal microbiota

Time: At 28 days

Secondary Outcomes

Description: Alterations in fecal microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls

Measure: Analysis of the faecal microbiota from rectal swab

Time: at baseline and every 7 days during 28 days

Description: Alterations in respiratory microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls

Measure: Analysis of the respiratory microbiota from the bronchoalveolar lavage liquid

Time: at baseline and every 7 days during 28 days

Description: Changes in blood, c-reactive protein, leucocyte, lymphocyte from baseline

Measure: Serum inflammatory markers changes

Time: at 28 days,

Description: changes in Cytokine/ chemokine from baseline

Measure: Inflammatory markers changes

Time: at 28 days,

Description: death

Measure: Mortality

Time: at 28 days,

Description: Number of days alive without mechanical ventilation

Measure: mechanical ventilation free days

Time: at 28 days,
123 PEEP Incremental and Decremental Alveolar Recruitment of Critically Ill COVID-19 Patients Under Electric Impedance Tomography (EIT)

COVID-19 originated from Severe Acut Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to critical condition due to hypoxemic respiratory failure with the background of viral pneumonia. Both alevolar recruitment and the subsequent optimal positive end-expiratory pressure (PEEP) adjustment has a pivotal role in the elimination of atelectasis developed by inflammation in the lung parenchyma The gold standard of the follow up of recruitment manoeuvre is the chest computed tomography (CT) examination. However, reduction of intrahospital transport and the exposure with healthcare workers are recommended because of the extremely virulent pathogen spreading easily by droplet infection. In this case bedside investigations have an utmost importance in the management of hygiene regulations. Electric impedance tomography (EIT) is a non-invasive, radiation free functional imaging technique easily applicable at the bedside.

NCT04360837
Conditions
  1. COVID-19
  2. Virus; Pneumonia
  3. Atelectasis
Interventions
  1. Procedure: alveolar recruitment
MeSH:Pneumonia, Viral Pneumonia Pulmonary Atelectasis
HPO:Atelectasis Pneumonia

Primary Outcomes

Description: Estimation of change in compliance (ml/cmH2O) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.

Measure: Changes in lung compliance

Time: 20 minutes

Description: Estimation of change in global impedance (%) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.

Measure: Change in global impedance

Time: 20 minutes

Description: Estimation of change in global impedance (%) on a daily manner.

Measure: Change in recruitability

Time: 7 days

Secondary Outcomes

Description: Change in arterial partial pressure of oxygen (PaO2) (mmHg) following recruitment

Measure: Gas exchange

Time: 20 minutes and 7 days

Description: Change in plateau pressure (cmH2O) following recruitment

Measure: Plateau pressure

Time: 20 minutes and 7 days

Description: Change in end expiratory lung impedance (%)

Measure: End expiratory lung impedance (EELI)

Time: 20 minutes and 7 days

Description: Change in antero-to-posterior ventilation ratio (%) following intervention

Measure: Antero-to-posterior ventilation ratio

Time: 20 minutes and 7 days

Description: Change in center of ventilation (%) following intervention

Measure: Center of ventilation

Time: 20 minutes and 7 days

Description: Change in global inhomogeneity index (%) following intervention

Measure: Global inhomogeneity index

Time: 20 minutes and 7 days
124 Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial

This trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.

NCT04360876
Conditions
  1. COVID-19
  2. ARDS
Interventions
  1. Drug: Dexamethasone injection
  2. Drug: Placebos
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.

Measure: Ventilator Free Days (VFD) at Day 28

Time: 28 Days

Secondary Outcomes

Description: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.

Measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.

Time: 14 Days

Measure: Clinical Status at day 28 as measured by WHO 7-point ordinal scale

Time: 28 Days

Measure: In-Hospital Mortality at day 28

Time: 28 Days

Measure: In-Hospital Mortality at day 90

Time: 90 Days

Measure: Time to Mortality to day 28

Time: 28 Days

Measure: ICU-free days to day 28

Time: 28 Days

Measure: Hospital Length of Stay among survivors to day 90

Time: 90 Days

Measure: Severity of ARDS to day 10

Time: 10 Days

Measure: Days to resolution of fever

Time: 28 Days

Measure: Change in C-Reactive Protein (CRP) level from baseline to day 10

Time: 10 Days

Measure: Vasopressor-free days to day 28

Time: 28 Days

Measure: Renal replacement-free days to day 28

Time: 28 Days

Measure: Duration of mechanical ventilation to day 28

Time: 28 Days

Measure: Oxygenation-free days to day 28

Time: 28 Days

Measure: Incidence of New Mechanical Ventilation to day 28

Time: 28 Days

Measure: Change in sequential organ failure assessment (SOFA) score from baseline to day 10

Time: 10 Days

Measure: In-hospital adverse events to day 28

Time: 28 Days

Measure: Discontinuation of study drug infusion

Time: 10 Days
125 Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)

Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

NCT04361942
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Biological: Mesenchymal Stromal Cells
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Index of therapy success to preserve Intensive Care Hospitalization space

Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation

Time: 0-7 days

Description: To measure global success

Measure: Rate of mortality

Time: 28 days

Secondary Outcomes

Description: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2

Measure: Proportion of patients who have achieved clinical response

Time: 0-7days

Description: Evaluation of pneumonia changes

Measure: Proportion of patients who have achieved radiological responses

Time: 0-28 days

Other Outcomes

Description: Haemogram and cell subpopulations

Measure: Blood white cell counts and their subpopulations.

Time: 0-180 days

Description: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs

Measure: Cellular markers of inflammation

Time: 0-180 days

Description: IL-10, IL-6, IP-10, TNF-alpha

Measure: Cytokines and chemokines in peripheral blood

Time: 0-180 days
126 Clinical Features and Risk Factors Associated With Worse Outcome in Patients Hospitalized for Covid-19 Pneumonia in France

The aim of the research is to improve patient management by rapidly identifying, based on the terrain and clinical and biological characteristics, those patients likely to present a severe form of ARDS at risk of leading to intensive care

NCT04362345
Conditions
  1. Covid-19
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Identification of risk factors for severity (death or transfer to resuscitation) of Covid-19 infection

Time: Files analysed retrospectively from March 1st, 2020 to April 15, 2020 will be examined]
127 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

NCT04362813
Conditions
  1. Pneumonia and Cytokine Release Syndrome (Covid-19)
Interventions
  1. Drug: Canakinumab
  2. Drug: Placebo
MeSH:Pneumonia Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.

Measure: Number of patients with clinical response

Time: Day 3 to Day 29

Secondary Outcomes

Description: COVID-19-related death during the 4-week period after study treatment.

Measure: COVID-19-related death rate during the 4-week period after study treatment

Time: 4 weeks

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the C-reactive protein (CRP)

Time: Baseline, Day 29

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the serum ferritin

Time: Baseline, Day 29

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the D-dimer

Time: Baseline, Day 29

Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).

Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs

Time: 127 days
128 Azithromycin With Amoxicillin/Clavulanate Versus Amoxicillin/Clavulanate Alone in COVID-19 Patients With Pneumonia and Hospitalized in a Non-intensive Care Unit Ward (AziA): a Superiority Open-label Randomized Controlled Trial

The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.1 As of April 14, 2020, there have been more than 1.5 million reported cases and 124 000 deaths in more than 200 countries. A recent open-label nonrandomized French study reporte that addition of azithromycin to hydroxychloroquine in 6 patients resulted in numerically superior viral clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%) or control (2/16, 12.5%). Azithromycin alone has never been tested, whereas azithromycin has immunomodulating and anti-inflammatory properties that could theoretically prevent or limit secondary worsening. Our hypothesis is that azithromycin combined with amoxicillin/clavulanate will be superior to amoxicillin/clavulanate alone to obtain viral clearance at Day 6 in COVID-19 patients with pneumonia and hospitalized in a non-intensive care unit ward.

NCT04363060
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Combination Product: Azithromycin with amoxicillin/clavulanate
  2. Drug: amoxicillin/clavulanate
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

Measure: Rate of positive SARS-CoV-2 RT-PCR

Time: Day 6

Secondary Outcomes

Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

Measure: Rate of positive SARS-CoV-2 RT-PCR

Time: Day 10

Description: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)

Measure: Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19

Time: day 6, day 10, and day 30

Description: Total duration of antibiotic treatment during the 30 days following inclusion

Measure: Total duration of antibiotic treatment during the 30 days following inclusion

Time: 30 days

Description: Number of all-cause mortality during the 30 days following inclusion

Measure: Number of all-cause mortality during the 30 days following inclusion

Time: 30 days

Description: Number of in-hospital mortality during the 30 days following inclusion

Measure: Number of in-hospital mortality during the 30 days following inclusion

Time: 30 days

Description: Number of patients transferred to intensive care unit during the 30-day follow-up

Measure: Number of patients transferred to intensive care unit during the 30-day follow-up

Time: 30 days

Description: Number of days without mechanical ventilation during the 30 days following inclusion

Measure: Number of days without mechanical ventilation during the 30 days following inclusion

Time: 30 days

Description: adverse events attributable to antibiotic treatment during the 30 days following inclusion

Measure: adverse events attributable to antibiotic treatment during the 30 days following inclusion

Time: 30 days

Description: Hospital length of stay during the 30 days following inclusion

Measure: Hospital length of stay during the 30 days following inclusion

Time: 30 days
129 Impact of Obstructive Sleep Apnea on Covid-19 Outcomes (OSACOVID-19 Study): A Prospective Observational Cohort Study

Covid-19 infection is an on-going pandemic with worse diagnosis in adults with comorbid conditions such as hypertension and cardiopulmonary diseases. Obstructive sleep apnea (OSA) is common in those comorbidities and may contribute to worse prognosis for the Covid-19 cases.

NCT04363333
Conditions
  1. COVID
  2. Obstructive Sleep Apnea
  3. Pneumonia
Interventions
  1. Diagnostic Test: Home Sleep Apnea Testing or In-hospital Polysomnography
MeSH:Apnea Sleep Apnea Syndromes Pneumonia Sleep Apnea, Obstructive
HPO:Apnea Obstructive sleep apnea Pneumonia Sleep apnea

Primary Outcomes

Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

Measure: The rate of clinical improvement

Time: 7 days

Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

Measure: The rate of clinical improvement

Time: 14 days

Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

Measure: The rate of clinical improvement

Time: 21 days

Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

Measure: The rate of clinical improvement

Time: 28 days

Secondary Outcomes

Description: Time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality

Measure: Clinical status - improvement

Time: 7, 14, 21, 28 days

Description: Defined as an increase in category on a 7-category ordinal scale from admission

Measure: Clinical status - worsening

Time: 7, 14, 21, 28 days

Other Outcomes

Description: Re-analysis of the correlation of obstructive sleep apnea (objectively verified) severity in terms of apnea-hypopnea index and oxygenation levels with the primary and secondary outcomes as described above (the rate of clinical improvement defined as a decline of 2 categories from admission on a 7-category ordinal scale; time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality as well as with the lung function, CO-diffusion capacity, cardiac function, CT thorax pathologies, biomarkers (cytokines, polymorphisms) and IgG-antibodies after 4 months.

Measure: Long-term outcomes

Time: 4-6 months after the initial hospital admission
130 A Phase-II, Open-Label, Randomized, Multicenter Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of 8 mg/kg or 4mg/kg Intravenous Tocilizumab in Patients With Moderate to Severe COVID-19 Pneumonia

This study will assess the pharmacodynamics, pharmacokinetics, safety and efficacy of two different doses of tocilizumab (TCZ) in combination with standard-of-care (SOC) in hospitalized adult participants with moderate to severe COVID-19 pneumonia.

NCT04363736
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Tociliuzumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Serum Concentration of interleukin-6 (IL-6) Following Administration of 8 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of 8 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of Ferritin Following Administration of 8 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of C-reactive Protein (CRP) Following Administration of 8 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of IL-6 Following Administration of 4 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of sIL-6R Following Administration of 4 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of Ferritin Following Administration of 4 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Measure: Serum Concentration of CRP Following Administration of 4 mg/kg IV TCZ

Time: At pre-defined intervals from first TCZ administration to Day 28

Secondary Outcomes

Measure: Pecentage of Participants with Adverse Events

Time: Up to Day 28

Measure: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time

Time: Up to Day 28

Measure: Time to Real-Time Polymerase Chain Reaction (RT-PCR) Virus Negativity

Time: Up to Day 28

Measure: Proportion of Participants with any Post-Treatment Infection

Time: Up to Day 28
131 A Prospective, Open-label, Randomized Pilot Study (Including a Control Group) of BACTEK-R (MV130), Administered Sublingually to Assess the Clinical Impact in Subjects With Mild Pneumonia Due to COVID-19

The purpose of the study is to confirm if BACTEK-R (MV130) provides clinical benefit in subject with mild pneumonia (CURB-65≤2) by COVID-19 admitted to the Hospital.

NCT04363814
Conditions
  1. COVID-19
Interventions
  1. Biological: Bactek-R
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of subjects presenting a improvement in their clinical condition from day 1 to 14 that lead their hospital discharged. Based on the measure of the secondary outcomes.

Measure: Clinical recovery

Time: 2 weeks

Description: Number of subjects presenting a worsening in their clinical condition from day 1 to 14 that leads to their admission to the intensive care unit or their death. Based on the measure of the secondary outcomes.

Measure: Clinical worsening

Time: 2 weeks

Secondary Outcomes

Description: Symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) will be daily record and classified as mild, moderate, severe.

Measure: Clinical severity

Time: 2 weeks

Description: Time of reduction or disappearance of the symptoms

Measure: Time to symptoms remission

Time: 2 weeks

Description: Record of all the medication administered to the subject

Measure: Medication Use

Time: 2 weeks

Description: Time from the subject's admission to the coronavirus unit until discharge

Measure: Hospitalization time

Time: 2 weeks

Description: Blood routine test will be carried out days 1 and 7

Measure: Blood routine test

Time: Days 1 and 7

Description: Heart rate will be followed everyday during time frame

Measure: Heart rate

Time: 2 weeks

Description: Blood pressure will be followed everyday during time frame

Measure: Blood pressure

Time: 2 weeks

Description: Cardiac auscultation will be recorded everyday during time frame

Measure: Cardiac auscultation

Time: 2 weeks

Description: Blood oxygen saturation will be followed everyday during time frame

Measure: Oxygen saturation

Time: 2 weeks

Description: Adverse events during treatment

Measure: Adverse events

Time: 2 weeks
132 A Phase I/II Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) for the Treatment of Adults With COVID-19

This study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in patients with moderate COVID-19 disease.

NCT04365101
Conditions
  1. Coronavirus
  2. Coronavirus Infection
  3. Severe Acute Respiratory Syndrome Coronavirus 2
  4. Pneumonia
  5. Pneumonia, Viral
  6. Lung Diseases
  7. Respiratory Tract Disease
  8. Respiratory Tract Infections
  9. Coronaviridae Infections
  10. Nidovirales Infections
  11. RNA Virus Infections
  12. Virus Disease
  13. Immunologic Disease
  14. ARDS
  15. Immunologic Factors
  16. Physiological Effects of Drugs
  17. Antiviral Agents
  18. Anti-infective Agents
  19. Analgesics
  20. Antimetabolites, Antineoplastic
Interventions
  1. Biological: CYNK-001
MeSH:Infection Communicable Diseases Respiratory Tract Infections Virus Diseases Coronavirus I Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral RNA Virus Infections Coronaviridae Infections Nidovirales Infections Pneumonia Lung Diseases Respiratory Tract Diseases Immune System Diseases
HPO:Abnormal lung morphology Pneumonia Respiratory tract infection

Primary Outcomes

Description: Number and severity of adverse events

Measure: Phase 1: Frequency and Severity of Adverse Events (AE)

Time: Up to 6 months

Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

Measure: Phase 1: Rate of clearance of SARS-CoV-2

Time: Up to 6 months

Description: Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score.

Measure: Phase 1: Rate of clinical improvement

Time: Up to 6 months

Description: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.

Measure: Phase 2: Time to Clearance of SARS-CoV-2

Time: Up to 28 days

Description: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.

Measure: Phase 2: Time to Clinical Improvement by NEWS2 Score

Time: Up to 28 days

Secondary Outcomes

Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

Measure: Rate of Clearance of SARS-CoV-2

Time: Up to 6 months

Description: Number and severity of adverse events

Measure: Phase 2: Frequency and Severity of Adverse Events (AE)

Time: up to 6 months

Description: Time to medical discharge as an assessment of overall clinical benefit

Measure: Overall Clinical Benefit by time to medical discharge

Time: up to 6 months

Description: Hospital utilization will be measured as an assessment of overall clinical benefit

Measure: Overall Clinical Benefit by hospital utilization

Time: up to 6 months

Description: Mortality rate will be measured as an assessment of overall clinical benefit

Measure: Overall Clinical Benefit by measuring mortality rate

Time: up to 6 months

Description: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.

Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score

Time: Up to 28 days

Description: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).

Measure: Time to Pulmonary Clearance

Time: Up to 28 days

Description: For ventilatory support subjects, the days with supplemental oxygen-free.

Measure: Supplemental oxygen-free days

Time: Up to 28 days

Description: Proportion of subjects who need invasive or non-invasive ventilation

Measure: Proportion of subjects requiring ventilation

Time: Up to 28 days
133 Protective Effect of Aspirin on COVID-19 Patients

COVID-19 has a high infection rate and mortality, and serious complications such as heart injury cannot be ignored. Cardiac dysfunction occurred in COVID-19 patients, but the law and mechanism of cardiac dysfunction remains unclear. The occurrence of progressive inflammatory factor storm and coagulation dysfunction in severe and fatal cases of NCP points out a new direction for reducing the incidence of severe and critically ill patients, shortening the length of duration in severe and critically ill patients and reducing the incidence of complications of cardiovascular diseases. Aspirin has the triple effects of inhibiting virus replication, anticoagulant and anti-inflammatory, but it has not received attention in the treatment and prevention of NCP. Although Aspirin is not commonly used in the guidelines for the treatment of NCP, it was widely used in the treatment and prevention of a variety of human diseases after its first synthesis in 1898. Subsequently, aspirin has been confirmed to have antiviral effect on multiple levels. Moreover, one study has confirmed that aspirin can inhibit virus replication by inhibiting prostaglandin E2 (PGE2) in macrophages and upregulation of type I interferon production. Subsequently, pharmacological studies have found that aspirin as an anti-inflammatory and analgesic drug by inhibiting cox-oxidase (COX). Under certain conditions, the platelet is the main contributor of innate immune response, studies have found that in the lung injury model in dynamic neutrophil and platelet aggregation. In summary, the early use of aspirin in covid-19 patients, which has the effects of inhibiting virus replication, anti-platelet aggregation, anti-inflammatory and anti-lung injury, is expected to reduce the incidence of severe and critical patients, shorten the length of hospital duration and reduce the incidence of cardiovascular complications.

NCT04365309
Conditions
  1. Novel Coronavirus Pneumonia
  2. Aspirin
  3. Treatment
Interventions
  1. Drug: Aspirin 100mg
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: TTCR is defined as the study treatment (oral aspirin enteric-coated tablet) began to fever, breathing rate, blood oxygen saturation recovery, and cough relieving for at least 72 hours.

Measure: clinical recovery time (TTCR)

Time: not more than 14 days

Description: Time of SARS-CoV2 in upper respiratory tract specimens overcasting detected by RT-PCR.

Measure: the time of SARS-CoV2 overcasting

Time: not more than 37 days
134 Effect of Treatments in Patients Hospitalized for Severe COVID-19 Pneumonia: a Multicenter Cohort Study

Several treatments have been used in during the Covid-19 pandemic of 2020. Using patients' registries from several hospitals in Paris, the investigators retrospectively analyzed associations between specific treatments, including but not limited to hydroxychloroquine, azithromycin, remdesivir, baricitinib, tocilizumab, sarilumab, lopinavir/ritonavir and oseltamivir; and clinical outcomes including, death and mechanical ventilation.

NCT04365764
Conditions
  1. Covid-19
  2. ARDS
  3. Pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Composite of death and mechanical ventilation (i.e. intubation)

Measure: Composite of death and mechanical ventilation

Time: 14-days follow-up

Secondary Outcomes

Description: Death

Measure: Death

Time: 14-days follow-up

Description: Enabled by intubation

Measure: Mechanical ventilation

Time: 14-days follow-up

Description: Composite of death and mechanical ventilation

Measure: Composite of death and mechanical ventilation

Time: 28-days follow-up

Description: World Health Organization score

Measure: World Health Organization score

Time: 14-days follow-up

Description: World Health Organization score

Measure: World Health Organization score

Time: 28-days follow-up
135 Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated With Modulation of the Gut Microbial Flora

Italy was the first European country affected by a severe outbreak of the Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic emerged from Wuhan region (China), with a high morbidity and mortality associated with the disease. In light of its pandemic spread and the very limited therapeutic options, COronaVIrus Disease 19 (COVID-19) is considered an unprecedented global health challenge. Therefore, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19. Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.

NCT04366089
Conditions
  1. COVID
  2. SARS-CoV 2
  3. Pneumonia, Viral
  4. Coronavirus Infection
Interventions
  1. Other: Oxygen-ozone therapy, probiotic supplementation and Standard of care
  2. Dietary Supplement: SivoMixx (200 billion)
  3. Drug: Azithromycin
  4. Drug: hydroxychloroquine
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Comparison between the two groups

Measure: Delta in the number of patients requiring orotracheal intubation despite treatment

Time: 21 days

Secondary Outcomes

Description: Comparison between the two groups

Measure: Delta of crude mortality

Time: 21 days

Description: Comparison between the two groups

Measure: Delta of length of stay for patients in hospital

Time: 90 days

Description: Comparison between the two groups

Measure: delta in the value of interleukin (IL)-1

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of IL-6

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of IL-10

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of Tumor Necrosis Factor (TNF)-alpha

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of CD8+ CD38/ HLA-DR

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of fecal calprotectin

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of lipopolysaccharide (LPS)

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of zonulin

Time: 21 days

Description: Comparison between the two groups

Measure: delta in the value of alpha1-antitrypsin

Time: 21 days
136 Phase I / II Clinical Trial, Multicenter, Randomized and Controlled, to Assess the Safety and Efficacy of Intravenous Administration of Allogeneic Adult Mesenchymal Stem Cells of Expanded Adipose Tissue in Patients With Severe Pneumonia Due to COVID-19

Phase I/II clinical trial to evaluate the safety and efficacy of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cells Expanded in patients with severe COVID-19 pneumonia

NCT04366323
Conditions
  1. Sars-CoV2
Interventions
  1. Drug: ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Safety of the administration of allogeneic mesenchymal stem cells derived from adipose tissue assessed by Adverse Event Rate

Time: 12 months

Measure: Efficacy of the administration of allogeneic mesenchymal stem cells derived from adipose tissue assessed by Survival Rate

Time: 28 days
137 Thrombo Embolic Events in Critical Care Patients With Covid-19 Serious Acute Pneumopathy

The understanding of haemostasis and inflammation cross-talk has gained considerable knowledge during the past decade in the field of arterial and venous thrombosis. Complex and delicately balanced interaction between coagulation and inflammation involve all cellular and humoral components. Elements of the coagulation system such as activated thrombin, fibrinogen or factor Xa may increase inflammation by promoting the production of pro-inflammatory cytokines, chemokines, growth factors and adhesion molecules that lead to a procoagulant state amplifying the pathological process. Recent evidence supports inflammation as a common pathogenic contributor to both arterial and venous thrombosis, giving rise to the concept of inflammation-induced thrombosis. Patients with infection of COVID-19 and severe pneumoniae seem to have higher risk of thromboembolism. Very few data are available regarding the biological disorders of coagulation in these patients. Th purpose of this project is to analyze hemostasis and coagulation of patients with infection of COVID-19 and severe pneumonia.

NCT04366752
Conditions
  1. COVID-19
  2. Pneumonia
  3. ARDS
  4. Hemostasis
  5. Coagulation
Interventions
  1. Other: venous ultrasound
  2. Other: blood sample
MeSH:Pneumonia Thromboembolism
HPO:Pneumonia Thromboembolism

Primary Outcomes

Description: The reference range for the thrombin time is usually less than 20 seconds (ie, 15-19 seconds)

Measure: Variation of thrombin time (in secondes) in Covid-19 patients with pneumonia admitted in ICU.

Time: up to 6 weeks

Description: Variation of factor V concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

Measure: Variation of factor V concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

Time: up to 6 weeks

Description: Variation of factor II concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

Measure: Variation of factor II concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

Time: up to 6 weeks

Description: Variation of concentration of fibrin and fibrinogen degradation products (≥ 10 µgm/mL) in Covid-19 patients with pneumonia admitted in ICU.

Measure: Variation of concentration of fibrin and fibrinogen degradation products (≥ 10 µgm/mL) in Covid-19 patients with pneumonia admitted in ICU.

Time: up to 6 weeks
138 The RESCUE 1-19 Trial: Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19

This phase I/II trial studies low-dose radiation therapy as a focal anti-inflammatory treatment for patients with pneumonia or SARS associated with COVID-19 infection.

NCT04366791
Conditions
  1. Pneumonia
  2. Coronavirus Infection in 2019 (COVID-19)
  3. Severe Acute Respiratory Syndrome (SARS) Pneumonia
Interventions
  1. Radiation: Low Dose Radiation Therapy
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The rate will be reported, along with a two-sided 95% exact binomial confidence interval, using the Clopper-Pearson method. The observed extubation rate will be compared to the null rate of 20% using a two-sided binomial test. Statistical significance is assessed at the 0.05 level.

Measure: Rate of extubation (for intubated patients)

Time: Screening up to 28 days after radiation therapy

Secondary Outcomes

Description: Temperature in degrees (F)

Measure: Clinical outcome - Temperature

Time: Screening up to 28 days after radiation therapy

Description: Heart rate in beats per minutes

Measure: Clinical outcome - Heart Rate

Time: Screening up to 28 days after radiation therapy

Description: Systolic blood pressure in mm Hg

Measure: Clinical outcome - Systolic blood pressure

Time: Screening up to 28 days after radiation therapy

Description: Oxygen saturation in percentage

Measure: Clinical outcome - Oxygenation

Time: Screening up to 28 days after radiation therapy

Description: Respiratory rate in breaths per minute

Measure: Clinical outcome - Respirations

Time: Screening up to 28 days after radiation therapy

Description: FI02 in percentage

Measure: Clinical outcome - FiO2

Time: Screening up to 28 days after radiation therapy

Description: Positive end expiratory pressure (PEEP) in cm H20

Measure: Clinical outcome - PEEP

Time: Screening up to 28 days after radiation therapy

Description: Tidal volume in mL

Measure: Clinical outcome - Tidal volume

Time: Screening up to 28 days after radiation therapy

Description: Extubation/intubation events in percentage

Measure: Clinical outcome - Intubation/Extubation events

Time: Screening up to 28 days after radiation therapy

Description: Survival in percentage

Measure: Clinical outcome - Overall survival

Time: Screening up to 28 days after radiation therapy

Description: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.

Measure: Radiographic outcome - Chest xray

Time: Screening up to 28 days after radiation therapy

Description: CT scans with volume of consolidation measured in cubic centimeters.

Measure: Radiographic outcome - CT can

Time: Screening up to 28 days after radiation therapy

Description: White blood cell count in cell count x 10^3/mcL

Measure: Serologic outcome - WBC

Time: Screening up to 28 days after radiation therapy

Description: Hemoglobin in gm/dL

Measure: Serologic outcome - Hgb

Time: Screening up to 28 days after radiation therapy

Description: Procalcitonin in ng/mL

Measure: Serologic outcome - Procalcitonin

Time: Screening up to 28 days after radiation therapy

Description: Absolute neutrophil count in cell count x 10^3/mcL

Measure: Serologic outcome - ANC

Time: Screening up to 28 days after radiation therapy

Description: Creatine kinase in units/L

Measure: Serologic outcome - Creatine kinase

Time: Screening up to 28 days after radiation therapy

Description: Myoglobin in ng/mL

Measure: Serologic outcome - Myoglobin

Time: Screening up to 28 days after radiation therapy

Description: Albumin in gm/dL

Measure: Serologic outcome - Albumin

Time: Screening up to 28 days after radiation therapy

Description: Coagulation pathway time in seconds

Measure: Serologic outcome - PT/PTT

Time: Screening up to 28 days after radiation therapy

Description: D-Dimer in ng/mL

Measure: Serologic outcome - D-Dimer

Time: Screening up to 28 days after radiation therapy

Description: Gamma-glutamyl transferase in units/L

Measure: Serologic outcome - GGT

Time: Screening up to 28 days after radiation therapy

Description: Trygliciericdes in mg/dL

Measure: Serologic outcome -Triglycerides

Time: Screening up to 28 days after radiation therapy

Description: Ferritin in ng/mL

Measure: Serologic outcome -Ferritin

Time: Screening up to 28 days after radiation therapy

Description: Fibrinogen in mg/dL

Measure: Serologic outcome -Fibrinogen

Time: Screening up to 28 days after radiation therapy

Description: Immune marker flow cytometry (refractive index)

Measure: Serologic Immune markers flow cytometry

Time: Screening up to 28 days after radiation therapy

Description: Bilirubin in mg/dL

Measure: Serologic outcome -Bilirubin

Time: Screening up to 28 days after radiation therapy

Description: Lactate Dehydrogenase in units/L

Measure: Serologic outcome - LDH

Time: Screening up to 28 days after radiation therapy

Description: Creatinine in mg/dL

Measure: Serologic outcome - Creatinine

Time: Screening up to 28 days after radiation therapy

Description: Estimated Glomerular Filtration Rate in mL/min/m2

Measure: Serologic outcome - EGFR

Time: Screening up to 28 days after radiation therapy

Description: C-Reactive Protein in mg/L

Measure: Serologic outcome - CRP

Time: Screening up to 28 days after radiation therapy

Description: Alanine Aminotransferase in units/L

Measure: Serologic outcome - ALT

Time: Screening up to 28 days after radiation therapy

Description: Asparatate Aminotransferase in units/L

Measure: Serologic outcome - AST

Time: Screening up to 28 days after radiation therapy

Description: Troponin-I in ng/mL

Measure: Serologic outcome - Troponin-I

Time: Screening up to 28 days after radiation therapy

Description: B-Natriuretic Peptid in pg/mL

Measure: Serologic outcome - BNP

Time: Screening up to 28 days after radiation therapy

Description: pH (no unit)

Measure: Serologic outcome - Blood Gases pH

Time: Screening up to 28 days after radiation therapy

Description: pressure of O2 in mm Hg

Measure: Serologic outcome - Blood Gases pO2

Time: Screening up to 28 days after radiation therapy

Description: pressure of CO2 in mm Hg

Measure: Serologic outcome - Blood Gases pCO2

Time: Screening up to 28 days after radiation therapy

Description: Lactic Acid in mmol/L

Measure: Serologic outcome - Lactic Acid

Time: Screening up to 28 days after radiation therapy

Description: Interleukin-6 in pg/mL

Measure: Serologic outcome - IL-6

Time: Screening up to 28 days after radiation therapy

Description: Potassium in mmol/L

Measure: Serologic outcome - Potassium

Time: Screening up to 28 days after radiation therapy
139 Evaluation of the Impact of Bacteriotherapy in the Treatment of COVID-19

In light of its high morbidity and mortality, COronaVIrus Disease 19 (COVID-19) pandemic spread is considered an unprecedented global health challenge. Given the very limited therapeutic options available against Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic at this time, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an observational, retrospective, non-profit study on the adjuvant use of bacteriotherapy in the early control of disease progression in patients affected by COVID-19 and treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of bacteriotherapy in reducing the clinical impact of acute diarrhea, containing the progression of COVID-19 and preventing the need for hospitalization in intensive care units.

NCT04368351
Conditions
  1. COVID
  2. Pneumonia
  3. Diarrhea
Interventions
  1. Dietary Supplement: SivoMixx (200 billion)
  2. Drug: Azithromycin
  3. Drug: hydroxychloroquine
MeSH:Pneumonia Diarrhea
HPO:Diarrhea Pneumonia

Primary Outcomes

Description: Comparison between the two groups. Acute diarrhea was defined as a stool with increased water content, volume, or frequency that lasts less than 14 days.

Measure: delta of time of disappearance of acute diarrhea

Time: 21 days

Secondary Outcomes

Description: Comparison between the two groups

Measure: Delta in the number of patients requiring orotracheal intubation despite treatment

Time: 21 days

Description: Comparison between the two groups

Measure: Delta of crude mortality

Time: 21 days

Description: Comparison between the two groups

Measure: Delta of length of stay for patients in hospital

Time: 21 days
140 Platelet Inhibition With GP IIb/IIIa Inhibitor in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). A Compassionate Use Protocol

This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).

NCT04368377
Conditions
  1. Pneumonia, Viral
  2. Corona Virus Infection
  3. Respiratory Failure
  4. Embolism and Thrombosis
Interventions
  1. Drug: Tirofiban Injection
  2. Drug: Clopidogrel
  3. Drug: Acetylsalicylic acid
  4. Drug: Fondaparinux
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency Thrombosis Embolism Embolism and Thrombosis
HPO:Pneumonia Thromboembolism

Primary Outcomes

Description: Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment

Measure: P/F ratio

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

Measure: PaO2 difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.

Measure: A-a O2 difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Secondary Outcomes

Description: Number of days on continuous positive end expiratory pressure (CPAP)

Measure: CPAP duration

Time: From the first day of study drugs administration (T0) until day 7 post study drugs administration

Description: Difference in intensity of the respiratory support (non invasive mechanical ventilation, CPAP, high flow nasal cannula (HFNC), Venturi Mask, nasal cannula, from higher to lower intensity, respectively) employed at baseline and at 72 and 168 hours after study treatment initiation

Measure: In-hospital change in intensity of the respiratory support

Time: At baseline and 72 and 168 hours after treatment initiation

Description: Difference in partial pressure of carbon dioxide in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

Measure: PaCO2 difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Difference in concentration of bicarbonate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

Measure: HCO3- difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Difference in concentration of lactate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

Measure: Lactate difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Difference in hemoglobin concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.

Measure: Hb difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Difference in platelet concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.

Measure: Plt difference

Time: At baseline and 24, 48 and 168 hours after treatment initiation

Description: Any major or minor adverse effect occuring during and after the administration of the study drug (e.g. bleeding)

Measure: Adverse effects

Time: From the first day of study drugs administration until day 30 post study drugs administration
141 Intelligence-based Remote Pulmonary Rehabilitation and Efficacy Among Discharged COVID-19 Patients

The noval coronavirus disease 2019 (COVID-19) would cause physical and psychological dysfunctions in infected patients. We expect that an intelligence-based remote pulmonary rehabilitation scheme could improve patients' health status after hospital discharge. The intelligence-based remote pulmonary rehabilitation program is designed in a real-world and prospective manner, aiming to evaluate the efficacy of rehabilitation among 200 patients in the epicenter of China (Wuhan City) according to their varied adherence. An eight-week rehabilitation scheme, including two weeks for physicians and physiotherapists remotely guided training, and six weeks for patient self-management, will be addressed. The primary outcome of current study is six-minute walking distance and lung function, and secondly respiratory muscle strength, physical fitness assessment, symptoms and quality of life, etc. will also be assessed. Recruited patients will be followed up at week 2, 4, 8 after enrollment and at month 1, 3, 6, 12 after the rehabilitation training completed, respectively. The study has been approved by the ethics committee of China-Japan Friendship Hospital and three participating centers in Wuhan City.

NCT04368793
Conditions
  1. COVID-2019 Pneumonia
  2. Pulmonary Rehabilitation
Interventions
  1. Behavioral: Remote pulmonary rehabilitation
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Walking distance within six minutes

Measure: Six-minute walking distance (6MWD)

Time: One year

Description: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), etc.

Measure: Pulmonary function

Time: One year

Secondary Outcomes

Description: Maximal inspiratory pressure, maximal expiratory pressure, etc.

Measure: Respiratory muscle strength

Time: One year

Description: Two-minute walking test, short physical performance battery, grip strength of both upper limbs, knee extension strength of both lower limbs, etc.

Measure: Physical fitness assessment

Time: One year

Description: Modified British Medical Research Council (mMRC) dyspnea scale, etc.

Measure: Symptom

Time: One year

Description: Self-training depression scale (SDS) and self-rating anxiety scale (SAS)

Measure: Psychological evaluation

Time: One year

Description: 36-item short-form health survey (SF-36), etc.

Measure: Quality of life

Time: One year

Description: International physical activity questionnaire (IPAQ)

Measure: Physical activity

Time: One year

Description: Proportions of returning to routine work and normal life

Measure: Proportion of returning to society

Time: One year
142 A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared With Best Supportive Care in Patients With COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult patients with Coronavirus Disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Patients will be randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the patients) or BSC alone (1/3 of the patients). Best supportive care will consist of medical treatment and/or medical interventions per routine hospital practice.

NCT04369469
Conditions
  1. COVID-19 Severe Pneumonia
  2. Acute Lung Injury
  3. Acute Respiratory Distress Syndrome
  4. Pneumonia, Viral
Interventions
  1. Biological: Ravulizumab
  2. Other: Best Supportive Care
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Measure: Survival (based on all-cause mortality) at Day 29

Time: Baseline, Day 29

Secondary Outcomes

Measure: Number of days free of mechanical ventilation at Day 29

Time: Baseline, Day 29

Measure: Duration of intensive care unit stay at Day 29

Time: Baseline, Day 29

Measure: Change from baseline in Sequential Organ Failure Assessment at Day 29

Time: Baseline, Day 29

Measure: Change from baseline in SpO2/FiO2 at Day 29

Time: Baseline, Day 29

Measure: Duration of hospitalization at Day 29

Time: Baseline, Day 29

Measure: Survival (based on all-cause mortality) at Day 60 and Day 90

Time: Baseline, Day 60, Day 90
143 A Trial of Ozone Auto-hemotherapy in Adults Hospitalized With Covid-19 Pneumonia

This is a multicenter, randomized, controlled, open-label clinical trial testing the use of ozone auto-hemotherapy in hospitalized patients with Covid-19 pneumonia. Eligible patients will be randomly assigned to receive either ozone auto-hemotherapy plus standard treatment, or standard treatment alone. Patients in the ozone auto-hemotherapy group will receive treatment mixing 100-200ml of blood with ozone at a concentration of 40 μg / mL with a gas volume of 200 ml. Treatment will occur every 12h during 5 days. Standard treatment will be the one used in each hospital participating in the trial. All analyses will be done according to the intention-to-treat principle

NCT04370223
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Biological: Ozone auto-hemotherapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

Measure: Rate of patients achieving improvement in clinical condition at day 14 after recruitment

Time: 14 days

Secondary Outcomes

Description: mortality

Measure: Mortality at day 28

Time: 28 days

Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

Measure: Rate of patients achieving improvement in clinical condition at day 28 after recruitment

Time: 28 days

Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

Measure: Rate of patients achieving improvement in clinical condition at day 7 after recruitment

Time: 7 days

Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

Measure: Time to clinical improvement or hospital discharge

Time: 28 days

Description: Ventilator-free days from last extubation day until day 28 after recruitment

Measure: Number of ventilator-free days at 28 days

Time: 28 days

Description: Days hospitalized

Measure: Hospital length of stay

Time: 28 days

Description: Number of days until a 2-fold decrease in ferritin (ng/mL)

Measure: Time to a 2-fold decrease in ferritin

Time: 14 days

Description: Number of days until a 2-fold decrease in C-Protein Reactive (mg/L)

Measure: Time to a 2-fold decrease in C-protein reactive

Time: 14 days

Description: Number of days until a 2-fold decrease in Dimer-D (ng/mL)

Measure: Time to a 2-fold decrease in Dimer-D

Time: 14 days

Description: Number of days until a 2-fold decrease in Lactate Dehydrogenase (U/L)

Measure: Time to a 2-fold decrease in Lactate Dehydrogenase

Time: 14 days

Description: Number of days until a 2-fold decrease in Neutrophils to Lymphocytes ratio

Measure: Time to a 2-fold decrease in Neutrophils to Lymphocytes ratio

Time: 14 days
144 Accuracy of Lung Ultrasound in the Diagnosis of covid19 Pneumonia: a Multicenter Study in the Italian Outbreak

Is Lung Ultrasound really useful in diagnosing COVID19? What can be the usefulness of the Lung Ultrasound in the COVID19 epidemic? In the current state of the art, Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Lung Ultrasound in the diagnosis of COVID-19 are not yet known. Alveolar-interstitial lung diseases such as viral pneumonia and ARDS seems to have a specific ultrasound pattern that distinguishes them from bacterial pneumonia, preferentially represented by B lines, morphological irregularity of the pleural line, and small subpleural consolidations, but they could share these patterns with other pathologies, reducing specificity. In Italy, the Lung Ultrasound represents a consolidated method for the evaluation and management of all patients who come to the ER, and what we are sure of is its high sensitivity in identifying pathological patterns. Our preliminary data suggest that Lung Ultrasound is highly reliable not to include but to exclude the diagnosis of COVID-19 in patients with respiratory symptoms.

NCT04370275
Conditions
  1. COVID-19
  2. Pneumonia, Viral
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Lung Ultrasound accuracy in rule-out of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards

Measure: Negative Predictive Value of Lung Ultrasound in the diagnosis of COVID-19

Time: 30 days

Secondary Outcomes

Description: Lung Ultrasound accuracy in rule-in of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards

Measure: Positive Predictive Value of Lung Ultrasound in the diagnosis of COVID-19

Time: 30 days

Measure: Sensitivity and Specificity of Lung Ultrasound in the diagnosis of COVID-19

Time: 30 days
145 Tocilizumab in Hospitalized Cancer Patients With Coronavirus 2019 (SARS-CoV-2) and Severe Complications of Coronavirus Disease 19 (COVID-19)

This phase II expanded access trial will study how well tocilizumab works in reducing the serious symptoms including pneumonitis (severe acute respiratory distress) in patients with cancer and COVID-19. COVID-19 is caused by the SARS-CoV-2 virus. COVID-19 can be associated with an inflammatory response by the immune system which may also cause symptoms of COVID-19 to worsen. This inflammation may be called "cytokine storm," which can cause widespread problems in the body. Tocilizumab is a medicine designed to block the action of a protein called interleukin-6 (IL-6) that is involved with the immune system and is known to be a key factor for problems with excessive inflammation. Tocilizumab is effective in treating "cytokine storm" from a type of cancer immunotherapy and may be effective in reducing the inflammatory response and "cytokine storm" seen in severe COVID-19 disease. Treating the inflammation may help to reduce symptoms, improve the ability to breathe without a breathing machine (ventilator), and prevent patients from having more complications.

NCT04370834
Conditions
  1. Hematopoietic and Lymphoid Cell Neoplasm
  2. Malignant Solid Neoplasm
  3. Pneumonia
  4. Pneumonitis
  5. Severe Acute Respiratory Distress Syndrome
  6. Symptomatic COVID-19 Infection Laboratory-Confirmed
Interventions
  1. Biological: Tocilizumab
MeSH:Laboratory Infection Neoplasms Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
HPO:Neoplasm Pneumonia

Primary Outcomes

Measure: Clinical outcome as evaluated by the 7-category Clinical Status Ordinal Scale

Time: At least 60 days, up to 1 year
146 A Double-blind, Randomized Study Versus Placebo of Avdoralimab (IPH5401), an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia

The primary objective of this trial is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).

NCT04371367
Conditions
  1. COVID
Interventions
  1. Biological: avdoralimab
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: improvement of WHO ordinal scale

Measure: Clinical improvement using WHO ordinal scale

Time: day 28

Description: Number of days without mechanical ventilation at Day 28 for COVID-19 related Acute Respiratory Distress Syndrome (ARDS) Patients hospitalized in ICU

Measure: Number of ventilator-free days at Day 28 (VFD28)

Time: day 28

Secondary Outcomes

Measure: Number of participants with treatment-related adverse events

Time: day 28
147 Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019

The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 has seen numerous patients experiencing severe acute lung injury (ALI), which developed into severe respiratory distress syndrome (ARDS). The mortality was as high as 20% -40%. Due to the lack of effective antiviral treatments, supporting treatment is the predominant therapy for COVID-19 pneumonia. Its cure is essentially dependent on the patient's immunity. While the immune system eliminates the virus, numerous inflammatory cytokines are produced and a cytokine storm occurs in severe cases. Mesenchymal stem cells (MSCs) play an important role in injury repair and immune regulation, showing advantageous prospects in the treatment of COVID-19 pneumonia. MSCs prevent cytokine storms by retarding the TNF-α pathway, alleviate sepsis by modulating macrophages, neutrophils, NK cells, DC cells, T lymphocytes and B lymphocytes. After infused, MSCs aggregate in the lungs, improve the lung microenvironment, protect alveolar epithelia, and improve pulmonary fibrosis and pulmonary function.

NCT04371601
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Oseltamivir
  2. Drug: hormones
  3. Device: oxygen therapy
  4. Procedure: mesenchymal stem cells
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Improvement of pulmonary function

Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test

Time: 12 months

Secondary Outcomes

Description: Cytokines level

Measure: Detection of TNF-α levels, IL-10 levels

Time: 1,3,6,12months

Description: Immunological status

Measure: Detection of immune cells that secret cytokines, including CXCR3+, CD4+, CD8+, NK+ cells, and regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells).

Time: 1,3,6,12months

Description: Improvement of pulmonary function

Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test

Time: 1,3,6months

Description: Infection biomarkers

Measure: Changes of c-reactive protein and calcitonin

Time: 1,3,6,12months
148 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia

This study (EMPACTA) will a) evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia, and b) include an optional substudy to explore the long-term sequelae of resolved COVID-19 pneumonia.

NCT04372186
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Placebo
  2. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28

Time: Up to Day 28

Secondary Outcomes

Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

Time: Up to Day 28

Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

Time: Up to Day 28

Measure: Mortality Rate by Day 28

Time: Up to Day 28

Measure: Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen)

Time: Up to Day 28

Measure: Percentage of Participants with Adverse Events

Time: Up to Day 60

Measure: Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection

Time: Up to Day 60

Measure: Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline)

Time: Up to Day 60
149 VALIDATION OF A SEVERITY SCORE TO IDENTIFY PATIENTS ADMITTED FOR COVID-19 PNEUMONIA AT HIGH RISK FOR AN INTENSIVE APPROACH

The outbreak of the coronavirus disease 2019 (COVID-19), first merged in China in December 2019, is now becoming a Public Health Emergency, recently confirmed as a pandemic disease by the World Health Organization. In particular, since February 2020, a rapidly growing number of cases has been identified in Italy. The clinical picture of ranges from asymptomatic cases, mild upper respiratory tract infections to severe pneumonia with respiratory failure and death. In most severe cases, COVID-19 disease may be complicated by acute respiratory distress syndrome (ARDS), septic shock and multiorgan failure. It results fundamental to early identify those subjects who rapidly may worsen their clinical status, often requiring an intensive care unit (ICU) admission. It has been showed that, mainly in more severe forms of SARS-Cov-2 disease, there is the development of an hyperinflammatory status resembling a cytokine storm syndrome, as already reported in SARS patients. A recent study by Haung et al. reported that patients with COVID-19 infection showed high amounts of IL1B, IFN-gamma, IP10 and MCP1, probably linked to activated T-helper1 (Th1) cell responses. Those requiring ICU admission had higher levels of cytokines than those subjects not requiring ICU admission, thus suggesting that cytokine storm was associated with disease severity. A similarity between cytokine profile of COVID-19 disease and secondary haemophagocytic syndrome (sHLH) has been reported. Therefore, it was suggested to screen all patients with severe COVID-19 infection both for hyperinflammatory markers (like ferritin), and the HScore commonly used to generate a probability for diagnosis of sHLH (8), which includes some laboratory parameters like triglycerides, fibrinogen, ferritin, serum aspartate aminostransferase. Based on our experience on patients affected by pneumonia from Covid19, we have observed that those subjects with a more severe prognosis might have some predictive markers. We intend to verify if these markers can identify those subjects with Covid19 infection who need a more intensive therapy and to find a prognosis score.

NCT04372199
Conditions
  1. COVID
  2. Pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: To identify the best predictors of critical coronavirus pneumonia and to realize a simple severity score able to early classify high-risk individuals admitted to Internal Medicine Department for COVID-19 disease, needing an intensive approach

Time: 1 month
150 Epidemiology and Outcome of Ventilator-associated Pneumonia Among Critically Ill COVID-19 Patients

The aim of this study is to determine the risk factors for development of ventilator-associated pneumonia (VAP) and to identify the prognostic factors of VAP among Coronavirus Disease 2019 (CoViD-19) patients. We hypothesized that CoViD-19 serves as a high risk factor for the development of VAP and it affects clinical outcome measures negatively.

NCT04372576
Conditions
  1. Ventilator Associated Pneumonia
  2. Corona Virus Infection
Interventions
  1. Diagnostic Test: Assessment of ventilator-associated pneumonia criteria
MeSH:Pneumonia, Ventilator-Associated Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: 28-day all-cause mortality

Time: at study completion, anticipated 5 months

Secondary Outcomes

Measure: Days of mechanical ventilation

Time: average time frame expected 2-3 weeks

Measure: ICU length-of-stay

Time: average time frame expected 3-4 weeks

Measure: Antibiotic utilization

Time: average time frame expected 3-4 weeks (at discharge from ICU)

Measure: Ventilator-associated pneumonia rate

Time: at study completion, anticipated 5 months
151 Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC), in Collaboration With Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4)

Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host inflammatory response and activation of coagulation pathways. Macro- and micro-vascular thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic, anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive randomized controlled trial will determine whether therapeutic anticoagulation with heparin (subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus usual care reduces the need for intubation or death in hospitalized patients with COVID-19. The trial uses an adaptive design which was chosen to overcome limitations in available data to inform a priori estimation of event rates and possible effect sizes. The adaptive design also includes response-adaptive randomization based on baseline D-dimer level, probing for differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian adaptive randomized trial will stop at a conclusion 1) when the posterior probability that the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when the posterior probability that the proportional odds ratio is greater than 1.2 is less than 10% (definition of futility) or; 3) when the posterior probability that the proportional odds ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a maximum of 3,000 patients, although in many simulations the trial may require fewer patients. The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to accelerate evidence generation.

NCT04372589
Conditions
  1. COVID-19
  2. Pneumonia
Interventions
  1. Drug: Heparin
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The primary endpoint in the trial is days alive and free of organ support at day 21. This endpoint is defined as the number of days that a patient is alive and free of organ support through the first 21 days after trial entry. Organ support is defined as receipt of invasive or non-invasive mechanical ventilation, high flow nasal oxygen (>30 L/min), vasopressor therapy, or ECMO support. Death at any time (including beyond 21 days) during the index hospital stay is assigned the worst possible score of -1.

Measure: Mortality and days free of organ support

Time: 21 days

Secondary Outcomes

Description: A composite endpoint of death, deep vein thrombosis, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke collected during hospitalization or at 28 days and 90 days after enrollment (whichever is earlier).

Measure: Arterial and venous thrombotic conditions

Time: 28 days and 90 days

Description: Ordered categorical endpoint with three possible outcomes based on the worst status of each patient through day 30 following randomization: no invasive mechanical ventilation, invasive mechanical ventilation, or death.

Measure: Intubation and mortality

Time: 30 days

Measure: All-cause mortality

Time: 28 days and 90 days

Description: Invasive mechanical ventilation.

Measure: Intubation

Time: 30 days

Description: Days alive outside of the hospital through 28 days following randomization.

Measure: Hospital-free days

Time: 28 days

Description: Days alive not on a ventilator assessed at 28 days following randomization.

Measure: Ventilator-free days

Time: 28 days

Measure: Myocardial infarction

Time: 28 days and 90 days

Measure: Ischaemic stroke

Time: 28 days and 90 days

Description: Symptomatic proximal venous thromboembolism (DVT or PE).

Measure: Venous thromboembolism

Time: 28 days and 90 days

Description: Days alive not on a vasopressor assessed at 28 days following randomization.

Measure: Vasopressor-free days

Time: 28 days

Description: Days alive not on renal replacement assessed at 28 days following randomization.

Measure: Renal replacement free days

Time: 28 days

Description: Hospital re-admission within 28 days.

Measure: Hospital re-admission

Time: 28 days

Description: As defined by KDIGO criteria.

Measure: Acute kidney injury

Time: Duration of study

Measure: Systemic arterial thrombosis or embolism

Time: 28 days and 90 days

Description: Use of extracorporeal membrane oxygenation (ECMO) support.

Measure: ECMO support

Time: Duration of study

Description: Dialysis or ECMO.

Measure: Mechanical circuit thrombosis

Time: Duration of study

Description: Peak scale over 28 days, scale at 14 days, and proportion with improvement by at least 2 categories compared to enrollment, at 28 days.

Measure: WHO ordinal scale

Time: 28 days

Description: As defined by the International Society on Thrombosis and Haemostasis (ISTH).

Measure: Major bleeding

Time: Intervention period (maximum 14 days)

Description: Laboratory-confirmed.

Measure: Heparin-induced thrombocytopenia (HIT)

Time: Intervention period (maximum 14 days)
152 Early Short Course Corticosteroids in Hospitalized Patients With COVID-19

The investigators intend to study the role of early use of methylprednisolone in the hospitalized patients with a diagnosis of COVID-19 pneumonia.

NCT04374071
Conditions
  1. COVID
  2. Pneumonia, Viral
Interventions
  1. Drug: Methylprednisolone
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of patients transferred to ICU is each of the groups

Measure: Transfer to Intensive care unit (ICU)

Time: 14 days followup for every patient in each group

Description: Number of patients that needed mechanical ventilation in each of the groups

Measure: Need for Mechanical Ventilation

Time: 14 days followup for every patient in each group

Description: Number of patients who died in each of the groups

Measure: Mortality

Time: 14 days followup for every patient in each group

Secondary Outcomes

Description: Number of patients who developed ARDS of varying severity per Berlin classification in each of the groups

Measure: Development and Severity of ARDS

Time: 14 days followup for every patient in each group

Description: LOS in each of the groups

Measure: Length of hospital stay (LOS).

Time: 14 days followup for every patient in each group
153 Efficacy and Safety of High-Titer Anti-SARS-CoV-2 (COVID19) Convalescent Plasma for Hospitalized Patients With Infection Due to COVID-19 to Decrease Complications: A Phase II Trial

This is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.

NCT04374565
Conditions
  1. Corona Virus Infection
  2. SARS-CoV 2
  3. SARS Pneumonia
  4. Pneumonia
Interventions
  1. Drug: High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.

Measure: Transfer to ICU

Time: Days 0 - 60

Description: Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.

Measure: 28 day mortality

Time: Days 0 - 60

Secondary Outcomes

Description: Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.

Measure: Cumulative incidence of serious adverse events

Time: Days 0 - 60

Description: Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.

Measure: Rates and duration of SARS-CoV-2

Time: Days 0, 7, 14, and 21

Description: Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.

Measure: Serum of plasma antibody titer to SARS-CoV-2

Time: Days 0, 7, 14, and 28

Description: Blood will be collected and analyzed for cellular and humoral response.

Measure: Cellular and humoral immune response

Time: Days 0, 7, 14, 28

Description: All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.

Measure: Supplemental oxygen free days

Time: Days 0-28

Description: All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.

Measure: Ventilator free days

Time: Days 0 - 28

Description: All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.

Measure: ICU free days

Time: Days 0 - 28

Description: The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.

Measure: Sequential organ failure assessment score

Time: days 0, 1, 4, 7, 14, 21, 28

Description: Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.

Measure: Need for vasopressors

Time: Days 0 - 60

Description: Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.

Measure: Need for renal replacement therapy

Time: Days 0 - 60

Description: Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.

Measure: Need for extracorporeal membrane oxygenation (ECMO)

Time: Days 0 - 60

Description: Will be calculated from the date the patient entered the hospital until they were discharged.

Measure: Hospital length of stay (LOS)

Time: Days 0-60

Description: Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.

Measure: ICU LOS

Time: days 0 - 60

Description: All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.

Measure: Grade 3 or 4 Adverse Events (AEs)

Time: days 0 - 60
154 The Role of Sodium Bicarbonate as Adjuvant Treatment of Computed Tomography Identified COVID-19 Pneumonia: A Preliminary Report of Short Term Follow up

To report the possible role of S.B 8.4% in the treatment of COVID-19pneumonia.

NCT04374591
Conditions
  1. Pneumonia
  2. Covid19
Interventions
  1. Drug: Sodium Bicarbonate
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: defined as return of body temperature and relief of cough for more than 72 hours measured in days

Measure: Time to clinical recovery

Time: 7 days

Secondary Outcomes

Description: assessed by Chest CT defined as exacerbated, unchanged, moderately improved (with less than 50% pneumonia resolved) and significantly improved (with more than 50% pneumonia resolved).

Measure: Pulmonary recovery status

Time: 7 days
155 Prevalence of Long-term Respiratory Complications of Severe SARS-CoV-2 Pneumonia

Studies performed after coronavirus epidemics (severe acute respiratory syndrome coronavirus, SARS-CoV and Middle East respiratory syndrome coronavirus, MERS-CoV) have shown a long-term impact on respiratory morbidity, musculoskeletal and psycho-social repercussions. Patients with SARS-CoV pneumonia had fibrotic pulmonary sequelae at 45 days (lower DLCO in 27.3% of cases and radiological lesions in 21.5% of cases). In the MERS-CoV pneumonia study, patients had radiological sequelae in 33% of cases and the 12-month evaluation showed persistence of radiological abnormalities in 23.7% of the cases despite an improvement in respiratory function. Clinical presentation and therapeutic management of severe SARS-CoV-2 infection are in part similar to those induced by SARS-CoV and MERS-CoV. Long-term respiratory complications are therefore expected.

NCT04376840
Conditions
  1. Severe SARS-CoV2 Pneumonia
Interventions
  1. Other: Blood sample and data record
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Interstitial lung disease diagnosed with a thoracic CT-scan

Measure: medium-term respiratory complications

Time: 3 months

Secondary Outcomes

Description: Interstitial lung disease diagnosed with a thoracic CT-scan

Measure: long-term respiratory complications

Time: 12 months
156 Assessment of Extra Vascular Lung Water and Pulmonary Permeability by Transpulmonary Thermodilution in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Acute respiratory distress syndrome (ARDS) is a syndromic definition of an acute lung injury with alteration of biomechanics (lower respiratory system compliance) mostly associated with increased lesional edema. Increase in Pulmonary Vascular Permeability Index (PVPI) accompanied with accumulation of excess Extravascular Lung Water (EVLW) is the hallmark of ARDS. In routine clinical practice, the investigators measure the EVLW and PVPI in ARDS patients, as suggested by expert's recommendations, using a transpulmonary thermodilution (TPTD) technique. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly recognized illness that has spread rapidly throughout Wuhan (Hubei province) to other provinces in China and around the world. Most critically ill patients with SARS-CoV-2 will present the criteria for the definition of ARDS. However, many of these patients have a particular form of ARDS with severe hypoxemia often associated with near normal respiratory system compliance. This combination is almost never seen in severe ARDS. Thus other mechanisms (including probably vascular mechanisms), that are still poorly described, have to be involved in SARS-CoV-2. EVLW and PVPI have never been assessed in SARS-CoV-2 mechanically ventilated patients. The aim of this study is to evaluate these two parameters in order to best characterize and understand the mechanisms related to SARS-CoV-2. Based on observation of several cases in intensive care units (ICU), the investigators hypothesize that there are following different SARS-CoV-2 patterns: 1. Nearly normal compliance, low lung recruitability, normal EVLW and low PVPI. 2. Low compliance due to increased edema, high lung recruitability, high EVLW and high PVPI.

NCT04376905
Conditions
  1. COVID-19
  2. Pneumonia
  3. Acute Respiratory Distress Syndrome
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Acute Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Description: EVLW (ml/kg) measured by a PiCCO device using TPTD thermodilution

Measure: Changes of Extra Vascular Lung Water

Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3

Secondary Outcomes

Description: PVPI measured by a PiCCO device using TPTDventilation, duration of ICU length of stay, ICU mortality

Measure: Changes of Pulmonary Vascular Permeability Index

Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3

Description: Changes of pulmonary compliance (ml/mmHg)

Measure: Changes of pulmonary compliance

Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3
157 Pilot Study on the Feasibility of Low Dose Radiotherapy for SARS-Cov-2 Pneumonitis (COVID-19 Low Dose Radiotherapy - COLOR 19)

Low-dose radiotherapy treatment delivered to both lungs in patients with immune-related pneumonia following COVID-19 infection is backed up by biological and clinical bases that justify its use as a possible therapeutic option in these patients. This is a preliminary exploratory study (non-pharmacological interventional) to evaluate the feasibility and tolerability of low-dose radiotherapy treatment of SARS-Cov-2 immune-mediated pneumonia, for the subsequent implementation of a phase II study.This is a preliminary, monocentric, single-arm, interventional, non-pharmacological exploratory study. All enrolled patients will be treated with low-dose radiotherapy. Participants will undergo irradiation of the lungs, administered in a single fraction at the average prescription dose of 0.7 Gy (further details in the dedicated section).

NCT04377477
Conditions
  1. COVID-19
Interventions
  1. Radiation: Single fraction whole lung radiotherapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia, for the purpose of the subsequent implementation of a phase II study; lenght of hospital stay will be recorded

Measure: Lenght of hospital stay (days)

Time: Six months

Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia; the number of intensive care unit admissions will be recorded

Measure: Number of Intensive Care Unit admissions

Time: Six months

Secondary Outcomes

Description: Variation of the patient's score according to the Brescia COVID-19 Respiratory Severity Scale (minimum value 0, maximum value 8; higher scores mean a worse outcome) with baseline, assessed at 3, 6 and 10 days after treatment.

Measure: Variation of the Brescia COVID-19 Respiratory Severity Scale after treatment

Time: 3, 6 and 10 days

Description: Evaluation of the safety and tolerance of the low-dose radiotherapy treatment of SARS-Cov2 ( using the CTCAE 5.0 scale)

Measure: Occurence of CTCAE 5.0 adverse events

Time: 10 days and 6 months

Description: Variation of the radiological findings, assessed by chest X-ray (performed 3 and 6 days after treatment) and defined according to the Brixia scoring system (0-18 scale, with 18 meaning the worse outcome)

Measure: Variation of the chest X-ray radiological findings according to Brixia scoring system

Time: 3 and 6 days
158 The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation

Title: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation. This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death. This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.

NCT04377750
Conditions
  1. Covid19 Pneumonia
Interventions
  1. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: One-month mortality rate .

Measure: Survival

Time: One-month
159 Evaluation of Demographic and Clinical Parameters on Admission and Medications Used for Comorbidities in Patients With Covid-19 Pneumonia: A Single Center Experience in Turkey

Investigators will recruit patients diagnosed with COVID-19 pneumonia between March 11th, 2020 and April 15th, 2020 in emergency, internal medicine and cardiology outpatient clinics, retrospectively and analyze their clinical and demographic features on admission in regard to their medications used for chronic diseases regularly.

NCT04379310
Conditions
  1. Covid-19
Interventions
  1. Drug: ACE Inhibitors and Calcium Channel Blockers
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: number of segments involved on admission

Measure: extend of lung involvement

Time: 1 week

Description: hypoxia

Measure: oxygen saturation on admission

Time: 2 week
160 Low-dose Computed Tomography in COVID-19 Pneumonia: a Prospective Moscow Study

Hypothesis: low-dose chest computed tomography, has the same accuracy for the diagnosis of pneumonia compared to the routine protocol. In total, 230 patients are planned to be enrolled in the study. Each patient will have 2 studies (routine chest CT and low-dose chest CT) sequentially during one visit to the computed tomography room.

NCT04379531
Conditions
  1. Pneumonia
  2. Coronavirus Infection
Interventions
  1. Diagnostic Test: Low-dose Chest CT
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A standardized scale CT1-CT4 will be used. The expected correlation percentage is 90%.

Measure: Evaluate the correlation between standard CT and low-dose CT scans for the detection of community-acquired pneumonia.

Time: Upon completion, up to 1 year

Secondary Outcomes

Description: Expected threshold - 10 mm.

Measure: Threshold value of the infiltration zone size detected by low-dose CT scan compared to standard CT scan.

Time: Upon completion, up to 1 year

Description: Expected number - more than two zones.

Measure: Number of infiltration zones of pulmonary parenchyma corresponding to viral pneumonia detected by low-dose CT scan in comparison with standard CT scan.

Time: Upon completion, up to 1 year
161 Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19

This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.

NCT04380376
Conditions
  1. COVID-19
  2. Viral Pneumonia
Interventions
  1. Drug: Melphalan
  2. Other: Standard of care
MeSH:Pneumonia, Viral Pneumonia Respiratory Aspiration
HPO:Pneumonia

Primary Outcomes

Description: The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) Death Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT Hospitalized with intubation and mechanical ventilation Hospitalized on non-invasive ventilation or high flow oxygen. Hospitalized on a mask or nasal prongs. Hospitalized no oxygen therapy. Ambulatory, with limitation of activities. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.

Measure: The changes of COVID Ordinal Outcomes Scale

Time: baseline vs Day 14, day 28

Description: Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.

Measure: Percentage of the patients with Clinical Recovery

Time: baseline vs day 7, day 14, day 28

Description: The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.

Measure: The changes of the Borg's scale

Time: Baseline vs day 7, day 14, day 28

Secondary Outcomes

Description: Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.

Measure: CRP level

Time: baseline, day 7, Day 14, Day 28

Description: Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.

Measure: Lymphocyte count

Time: baseline, day 7, Day 14, Day 28

Description: Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.

Measure: D-dimer

Time: baseline, day 7, Day 14, Day 28

Description: Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.

Measure: IL-6

Time: baseline, day 7, Day 14, Day 28

Description: Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.

Measure: Percentage of patients without artificial lung ventilation

Time: baseline, day 7, Day 14, Day 28
162 Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study

Low radiation doses produce anti-inflammatory effects, which may be useful in the treatment of respiratory complications of COVID-19. This type of treatment is non-invasive and therefore, a priori, it can be used in all types of patients. Main objective: To evaluate the efficacy of low-dose lung irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to the pre baseline measurement. -irradiation.

NCT04380818
Conditions
  1. Pneumonia, Viral
Interventions
  1. Radiation: Low-dose radiotherapy
  2. Drug: Hydroxychloroquine Sulfate
  3. Drug: Ritonavir/lopinavir
  4. Drug: Tocilizumab Injection [Actemra]
  5. Drug: Azithromycin
  6. Drug: Corticosteroid
  7. Drug: Low molecular weight heparin
  8. Device: Oxygen supply
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To evaluate the efficacy of low-dose pulmonary irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to baseline pre-irradiation measurement. . In cases of impossibility the SaFiO2 will be determined

Measure: Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20%

Time: Day 2 after interventional radiotherapy

Secondary Outcomes

Description: Lung toxicity measured according to CTCAEv5

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Time: Day 30 and day 90 after interventional radiotherapy

Description: Chest CT

Measure: Change of the radiological image

Time: Days 7 and day 30 after interventional radiotherapy

Description: Death of any cause

Measure: Overall mortality

Time: Day 15 and Day 30 after interventional radiotherapy

Description: Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)

Measure: Measure of pro-inflammatory interleukins

Time: Days 1, day 4 and day 7 after interventional radiotherapy

Description: TGF-β (ng/ml)

Measure: Measure of trasforming growth factor (TGF-b)

Time: Days 1, day 4 and day 7 after interventional radiotherapy

Description: TNF-α (pg/ml)

Measure: Measure of tumor necrosis factor alpha (TNF-a)

Time: Days 1, day 4 and day 7 after interventional radiotherapy

Description: Overexpression of L-, E-, and P-selectin

Measure: Determining overexpression of pro-inflammatory selectin

Time: Days 1, day 4 and day 7 after interventional radiotherapy

Description: Overexpression of ICAM-1, VCAM

Measure: Determining cell adhesion molecules (CAMs)

Time: Days 1, day 4 and day 7 after interventional radiotherapy

Description: PON-1(paraoxonase and arylesterase activity) (IU/ml)

Measure: Measure of marker of oxidative stress PON-1

Time: Days 1, day 4 and day 7 after interventional radiotherapy
163 Inhalation of Ciclesonide for Patients With COVID-19: A Randomised Open Treatment Study (HALT COVID-19)

Randomized open label clinical trial carried out at study centers in Sweden, including Karolinska University Hospital, S:t Göran Hospital, Danderyd Hospital and Västmanlands Hospital. Patients with COVID-19 who are hospitalized with oxygen therapy are eligible for inclusion. Subjects are randomized to 14 days of inhalation with ciclesonide 360 µg twice daily or to standard of care. Primary outcome is duration of received supplemental oxygen therapy. Key secondary outcome is a composite outcome of death and received invasive mechanical ventilation within 30 days.

NCT04381364
Conditions
  1. Covid-19
  2. Pneumonia, Viral
  3. Sars-CoV2
Interventions
  1. Drug: Ciclesonide Inhalation Aerosol
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time (in days) of received supplemental oxygen therapy (defined as being alive and discharged from hospital to home or at least 48 h of not receiving oxygen therapy during hospitalization).

Measure: Duration of received supplemental oxygen therapy

Time: 30 days after study inclusion

Secondary Outcomes

Description: Rate of and time to (in days) received invasive mechanical ventilation or all-cause death

Measure: Invasive mechanical ventilation or all-cause death (key secondary outcome)

Time: 30 days after study inclusion

Description: Rate of and time to (in days) death of any cause

Measure: All cause death

Time: 30 days after study inclusion

Description: Rate of and time to (in days) received invasive mechanical ventilation

Measure: Invasive mechanical ventilation

Time: 30 days after study inclusion

Description: Level of remaining dyspnea symptoms according to the Modified Medical Research Council Dyspnea Scale

Measure: Remaining dyspnea symptoms

Time: 30-35 days and 5-7 months after inclusion
164 Efficacy and Safety of Convalescent Plasma vs Human Immunoglobulin for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Trial

Background: On December 2019, a new human coronavirus infection (COVID-19) was detected in China. Its infectivity and virulence characteristics caused a rapid spread, being declared pandemic on March 2020. The mortality attributed to the infection ranges between 3 and 10%. Main risk factors are age, male sex, and chronic degenerative comorbidities. Due to the absence of therapeutic options, potential alternatives such as human immunoglobulin or plasma from convalescent patients have been administered. Due to the severity of the disease and the associated mortality, it is urgent to find therapeutic alternatives. Objective: To assess the safety and efficacy of the administration of Convalescent plasma vs human immunoglobulin in critically ill patients with COVID-19 infection. Material and methods: Randomized Controlled trial of patients diagnosed with respiratory infection by COVID-19, with severe respiratory failure without indication of mechanical ventilation, or those who due to their severity are intubated upon admission. Randomization will be performed 2:1 to receive plasma from convalescent patients or human immunoglobulin. Outcomes: The primary outcome will be time to discharge from hospital for improvement. The safety outcomes will be: Kirby index (PaO2/FiO2) evolution and dead.

NCT04381858
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Plasma from COVID-19 convalescent patient
  2. Drug: Human immunoglobulin
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Mean days from admission as a suspected case of COVID with hospitalization criteria until discharge

Measure: Mean hospitalization time

Time: Through study completion, an average of 3 months

Description: Mean of delta of oxigenation index (PaO2/FiO2)

Measure: Mean Oxigenation index evolution

Time: Through study completion, an average of 3 months

Description: Rate of patients with evolution to severe ARDS (PaO2/FiO2 < 100)

Measure: Rate of severe ARDS

Time: Through study completion, an average of 3 months

Description: Rate of Dead caused by COVID-19 related complications and time to dead caused by COVID-19 complication

Measure: Rate and time to dead

Time: Through study completion, an average of 3 months

Description: Mean time with invasive mechanical ventilation

Measure: Mean time with invasive mechanical ventilation

Time: Through study completion, an average of 3 months

Secondary Outcomes

Description: Time to negativization of RT-qPCR SARS-CoV-2 test.

Measure: Time to Viral PCR Negativization

Time: Through study completion, an average of 3 months.
165 High Flow Nasal Oxygen Versus Continuous Positive Airway Pressure Helmet Evaluation: A Randomized Crossover Trial in COVID-19 Pneumonia

The purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.

NCT04381923
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. Hypoxemic Respiratory Failure
  3. Pneumonia, Viral
  4. COVID
Interventions
  1. Device: Helmet Continuous Positive Airway Pressure (CPAP)
  2. Device: High Flow Nasal Oxygen (HFNO)
MeSH:Coronavirus Infec Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: VFD is the number of days alive and free of mechanical ventilation in the first 28 days after study enrollment. Death before 28 days will be assigned a VFD equal to 0 to penalize non-survival. In cases of repeated intubation and extubation, periods free from invasive ventilation and lasting at least 24 consecutive hours will be calculated and summed. Timing of intubation and extubation will be captured in hours, and the number of hours a patient received invasive ventilation will be used to calculate duration of ventilation.

Measure: Ventilator-Free Days (VFD)

Time: 28 days

Secondary Outcomes

Description: Days spent in the ICU and hospital after time of enrollment

Measure: ICU and Hospital Length of Stay

Time: 28 days

Description: Incidence and time to intubation in days after the time of enrollment

Measure: Intubation

Time: 28 days

Description: Incidence of RRT after the time of enrollment

Measure: Renal Replacement Therapy (RRT)

Time: 28 days

Description: Death from any cause during after the time of enrollment

Measure: Mortality

Time: 28 days, 90 days
166 Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Patients With Coronavirus Disease 2019 (COVID-19) Pneumonia and Impaired Respiratory Function

The study will assess the efficacy and safety of DFV890 for the treatment of SARS-Cov-2 infected patients with COVID-19 pneumonia and impaired respiratory function.

NCT04382053
Conditions
  1. COVID 19 Pneumonia, Impaired Respiratory Function
Interventions
  1. Drug: DFV890
  2. Drug: Standard of Care (SoC)
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.

Measure: APACHE II severity of disease score on Day 15 or on the day of discharge (whichever is earlier)

Time: up to Day 15

Secondary Outcomes

Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.

Measure: Serum C-reactive protein (CRP) levels

Time: up to Day 29

Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

Measure: Clinical status over time

Time: up to Day 29

Description: Proportion of participants not requiring mechanical ventilation for survival.

Measure: Proportion of participants not requiring mechanical ventilation for survival.

Time: Day 15, Day 29

Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

Measure: Proportion of participants with at least one-point improvement from baseline in clinical status

Time: Baseline, Day 15, Day 29
167 Treatment of Covid-19 Associated Pneumonia With Allogenic Pooled Olfactory Mucosa-derived Mesenchymal Stem Cells

Treatment of patients with Covid-19 associated pneumonia using intravenous injection of allogenic pooled olfactory mucosa-derived mesenchymal stem cells

NCT04382547
Conditions
  1. COVID
  2. Covid-19
  3. Coronavirus
  4. Pneumonia
  5. Pneumonia, Viral
  6. Pneumonia, Interstitial
  7. Sars-CoV2
Interventions
  1. Biological: Allogenic pooled olfactory mucosa-derived mesenchymal stem cells
  2. Other: Standard treatment according to the Clinical protocols
MeSH:Pneumonia, Viral Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Number of patients cured, assessed by PCR in addition to chest CT scan

Measure: Number of cured patients

Time: 3 weeks

Secondary Outcomes

Description: MSC infusion related adverse events assessed by blood count, liver and function tests

Measure: Number of patients with treatment-related adverse events

Time: 3 weeks
168 Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial

Novel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.

NCT04382625
Conditions
  1. SARS-CoV-2 Pneumonia
  2. COVID-19
Interventions
  1. Drug: Hydroxychloroquine
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: paO2

Measure: Change from Baseline Oxygenation on Day 1 to Day 5

Time: Day 1 of treatment to day 5 of treatment

Description: FIO2

Measure: Change from Baseline Oxygenation at Day 5

Time: Day 1 of treatment to day 5 of treatment

Secondary Outcomes

Description: Length in hours

Measure: Intensive Care length of stay

Time: Day 0 to Day 28

Description: Length in hours

Measure: Required Mechanical Ventilation

Time: Day 0 to Day 28

Description: Length in hours

Measure: Required Oxygen supplementation

Time: Day 0 to Day 28

Description: Length in hours

Measure: Hospitalization length of Stay

Time: Day 0 to Day 28

Description: Date of Death

Measure: Mortality

Time: Day 0 to Day 28

Description: Cardiologist Diagnostic Documentation

Measure: Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia

Time: Day 0 to Day 28

Description: Cardiologist Diagnostic Documentation

Measure: Cardiac Arrhythmia - Ventricular Tachycardia

Time: Day 0 to Day 28

Description: Cardiologist Diagnostic Documentation

Measure: Cardiac Arrhythmia - Lengthening QTc

Time: Day 0 to Day 28
169 A Phase 2, Randomized, Placebo-controlled, Participant and Investigator Blinded, Multi-center Study to Assess Efficacy and Safety of MAS825 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function

The study will assess the efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function

NCT04382651
Conditions
  1. COVID-19 Pneumonia, Impaired Respiratory Function
Interventions
  1. Drug: MAS825
  2. Drug: Matching placebo
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.

Measure: APACHE II severity of disease score on Day 15 or on day of discharge (whichever is earlier)

Time: Up to 15 days

Secondary Outcomes

Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.

Measure: Serum C-reactive protein (CRP levels)

Time: Up to 15 days

Description: Ferritin is a blood test marker for inflammation in the body. For a standard Ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline Ferritin as a covariate.

Measure: Ferritin levels

Time: Up to 15 days

Description: Proportion of participants without the need for invasive mechanical ventilation for survival.

Measure: Proportion of participants without the need for invasive mechanical ventilation

Time: Day 15, Day 29

Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

Measure: Proportion of participants with at least one level improvement in clinical status

Time: Day 15, Day 29

Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

Measure: Clinical status over time

Time: Up to 15 days
170 Effects of Neuromuscular Electrical Stimulation Therapy on Physical Function in Patients With COVID-19 Associated Pneumonia: Study Protocol of a Randomized Controlled Trial

Neuromuscular electrical stimulation (NMES) has been considered as a promising approach for the early rehabilitation of patients in and/or after the intensive care unit (ICU). Aim of this study is to evaluate the NMES effect on physical function of COVID-19 patients.

NCT04382729
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Other: Neuromuscular Electrical Stimulation
  2. Other: Physical Therapy Exercise
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The SPPB score is a composite measure assessing standing balance (ability to stand for up to 10 seconds with feet positioned in three ways: together side-by-side, semi-tandem and tandem), walking speed (time to complete a 4-m walk), and sit-to- stand performance (time to rise from a chair five times). Each task is scored out of 4 points, with the scores from the three tests summed up to give a total, with a maximum of 12 points and a minimum of 0.

Measure: Short Physical Performance Battery (SPPB) Score

Time: 1 week after the intervention

Secondary Outcomes

Description: The FIM is an 18-item, clinician-reported scale that assesses function in six areas including self-care, continence, mobility, transfers, communication, and cognition. Each of the 18 items is graded on a scale of 1-7 based on level of independence in that item (1 = total assistance required, 7 = complete independence)

Measure: Functional Independence Measure (FIM) Scale Score

Time: Before and 1 week after the intervention

Description: The Fatigue Severity Scale is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle

Measure: Fatigue Severity Scale Score

Time: Before and 1 week after the intervention

Description: Handgrip strength is assessed for both sides using a handheld device. Patients are instructed to perform a maximal voluntary isometric contraction by contracting their muscles as forcefully as possible for 4-5 s. The test is repeated three times for each side and the highest value is retained. Lower limb strength is assessed as the sum of knee extension and plantar flexion strength of both sides. Muscle strength is rated using the Medical Research Council (MRC) scale that ranges from 0 (no muscle contraction) to 5 (normal resistance), for a maximum score of 20 points.

Measure: Muscle Strength

Time: Before and 1 week after the intervention

Description: Subjects are required to step out with the dominant leg maximally, then to step out with the other leg maximally, and then to draw and match the first leg to the second leg while maintaining body stability with either supporting leg. The distance between the start line and the tiptoe of the second step foot is measured as the double step length (sum of the first and second steps).

Measure: Two Step Test Length

Time: 1 week after the intervention

Description: The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.

Measure: Six Minutes Walking Test Distance

Time: 1 week after the intervention

Description: Ultrasound-derived muscle thickness is measured as the distance between the superficial and deep aponeuroses of the rectus femoris muscle (that is measured half-way along the line from the anterior-superior iliac spine to the superior border of the patella). Three consecutive static scans of the rectus femoris of both thighs are acquired in the transverse plane and the mean of six measurements (three measurements per side) is considered.

Measure: Muscle Thickness

Time: Before and 1 week after the intervention
171 Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

NCT04383535
Conditions
  1. SARS Virus
  2. SARS-CoV-2
  3. COVID-19
Interventions
  1. Other: Convalescent SARS COVID-19 plasma
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

Measure: Clinical status during follow-up at 30th day

Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Secondary Outcomes

Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

Measure: Clinical status during follow-up at 7th day

Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

Measure: Clinical status during follow-up at 14th day

Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Hospital discharge or intrahospital death

Measure: Time until hospital discharge (days).

Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

Description: ICU discharge or ICU death

Measure: Time until discharge from ICU (days)

Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

Description: Death and time to death

Measure: Time to death

Time: In a 30 days follow up period

Description: Time until complete functional recovery (according to basal status).

Measure: Time until complete functional recovery

Time: Whenever the patient returns to basal functional status until 1 month from discharge

Description: Percentage of participants with adverse events / serious adverse events

Measure: Percentage of participants with adverse events / serious adverse events

Time: In a 30 days follow up period

Description: Percentage of patients with negative SARS-CoV-3 PCR

Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th

Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: D Dimer plasma concentration

Measure: D Dimer plasma concentration at Day 14th

Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Ferritin plasma concentration

Measure: Ferritin plasma concentration at Day 13th

Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Plasma concentration of neutralizing antibodies

Measure: Plasma concentration of neutralizing antibodies at Day 2nd

Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Plasma concentration of neutralizing antibodies

Measure: Plasma concentration of neutralizing antibodies at Day 7th

Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Post-transfusion adverse reactions between study groups

Measure: Post-transfusion adverse reactions

Time: In a 30 days follow up period
172 Predicting Outcomes for Covid-19 Using Sonography

This study seeks to investigate the role of lung ultrasound in caring for Covid-19 positive patients and whether it can be used to predict patient deterioration. This information will be vital for healthcare workers who seek to identify Covid-19 pneumonia or patients at risk for deterioration early in the disease course.

NCT04384055
Conditions
  1. COVID-19
  2. Pneumonia, Viral
Interventions
  1. Diagnostic Test: Lung Ultrasound
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Composite primary outcome of death, ICU admission, mechanical ventilation, or use of high-flow nasal cannula (categorical)

Measure: Number of Patients Experiencing Death, ICU Admission, Mechanical Ventilation, or Use of High-Flow Nasal Cannula

Time: 28 days from initial evaluation

Secondary Outcomes

Measure: Number of Patients Requiring Mechanical Ventilation

Time: 28 days from initial evaluation

Measure: Number of Patients Requiring Supplemental Oxygen Usage

Time: 28 days from initial evaluation

Measure: Duration of Supplemental Oxygen Usage

Time: 28 days from initial evaluation

Description: Duration of Hospitalization (days)

Measure: Length of Stay

Time: 28 days from initial evaluation

Description: Descriptive analysis of ultrasound findings in Covid-19

Measure: Characterization of Ultrasound Findings

Time: 28 days from initial evaluation
173 Cytokine Adsorption in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation - Randomized, Controlled, Open-label Intervention, Multi-center Trial (CYCOV-II-study)

In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.

NCT04385771
Conditions
  1. Coronavirus Infection
  2. COVID
  3. SARS-CoV 2
  4. Respiratory Failure
  5. Cytokine Storm
  6. Extracorporeal Membrane Oxygenation
Interventions
  1. Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)
  2. Device: vv-ECMO only (no cytokine adsorption)
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)

Measure: IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement

Time: 72 hours

Description: time to successful ECMO-explantation within 30 days after randomization

Measure: time to successful ECMO-explantation

Time: 30 days

Secondary Outcomes

Description: Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization

Measure: Ventilator free days (VFD)

Time: 30 days

Description: Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.

Measure: Time to extubation from ventilation and explantation from ECMO

Time: 30 days

Description: Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.

Measure: Overall survival time

Time: 30 days

Description: Days on intensive care unit (ICU)

Measure: Days on intensive care unit (ICU)

Time: 30 days

Description: Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h

Measure: Vasopressor dosage

Time: 24, 48, 72 hours

Description: Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h

Measure: Fluid substitution and fluid balance

Time: 24, 48, 72 hours

Description: Serum lactate at 24, 48, 72 h

Measure: Serum lactate

Time: 24, 48, 72 hours

Description: Urine output at 24, 48, 72 h

Measure: Urine output

Time: 24, 48, 72 hours

Description: Willebrand factor at 24, 48, 72 h

Measure: Willebrand factor

Time: 24, 48, 72 hours

Description: d-dimers at 24, 48, 72 h

Measure: d-dimers

Time: 24, 48, 72 hours

Description: interleukin-6 levels at 24, 48, 72 h

Measure: interleukin-6 levels

Time: 24, 48, 72 hours

Description: Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)

Measure: SOFA-Score

Time: 24, 48, 72 hours

Description: serious complications or malfunctions related to the CytoSorb device

Measure: serious adverse device effects

Time: 30 days

Description: unintended air in the ECMO system during operation of the device

Measure: adverse event of special interest: air in the ECMO system

Time: 30 days

Description: unintended blood-clotting in the ECMO system during operation of the device

Measure: adverse event of special interest: blood-clotting in the ECMO system

Time: 30 days

Description: major bleeding events

Measure: adverse event of special interest: bleeding complications

Time: 30 days
174 Use of High Flow Nasal Cannula Oxygen During Acute Hypoxemic Respiratory Failure Related to Covid-19 and Interest of the Respiratory-oxygenation Index (ROX Index): an Observational Study

Nasal High Flow oxygen therapy (NHF) is commonly used as first line ventilatory support in patients with acute hypoxemic respiratory failure (AHRF). It's use has been initially limited in Covid-19 patients presenting with AHRF. The aim of the study is to describe the use of NHF in Covid-19-related AHRF and report the changes in the respiratory-oxygenation index (termed ROX index) over time in these patients.

NCT04385823
Conditions
  1. Respiratory Syndrome, Acute, Severe
  2. Hypoxic Respiratory Failure
  3. Viral Pneumonia
Interventions
  1. Device: patients receiving nasal high flow
MeSH:Pneumonia, Viral Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: values of ROX index during ICU stay

Measure: Changes in ROX index

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Secondary Outcomes

Description: percentage of patients requiring intubation

Measure: NHF failure

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Description: level of flow used with NHF

Measure: NHF flow

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Description: level of inspired fraction in oxygen used with NHF

Measure: NHF inspired fraction in oxygen

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Description: level of pulse oxymetry during NHF therapy

Measure: oxygenation

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Description: respiratory rate during NHF therapy

Measure: respiratory status

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Description: defining the values of ROX index associated with intubation

Measure: prediction of intubation

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

Description: defining the values of ROX index associated with NHF success (no intubation required)

Measure: prediction of NHF success

Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months
175 Long Term Functional Outcomes of COVID-19 Patients Treated by Rehabilitation Services viaTelehealth

This study seeks to assess the impact of physical and pulmonary rehabilitation on patients who have been diagnosed with COVID-19 in the short and long term in hopes of establishing a best practices protocol for treatment of future patients with this disease.

NCT04385901
Conditions
  1. SARS-CoV 2
  2. SARS Pneumonia
Interventions
  1. Behavioral: Therapy Intervention
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Validated test demonstrating functional gait capacity and endurance; measuring change in capacity over time in 6 month increments.

Measure: Change in 6 Minute Walk Test

Time: From 6 to 24 months post diagnosis

Description: Validated questionnaire assessing function and quality of life for patients with pulmonary function issues

Measure: Change in Short Form 35 (SF-36) Questionnaire

Time: From 6 to 24 months post diagnosis

Secondary Outcomes

Description: Use of grip dynamometer and isokinematic lower extremity testing to determine muscle capacity

Measure: Change in Strength testing

Time: From 6 to 24 months post diagnosis

Description: Measures lung output capacity

Measure: Change in Peak Flow Meter Test

Time: From 6 to 24 months post diagnosis
176 A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MSTT1041A or UTTR1147A in Patients With Severe COVID-19 Pneumonia

This is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) compared with placebo and of UTTR1147A compared with placebo, in combination with standard of care (SOC), in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.

NCT04386616
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: MSTT1041A
  2. Drug: MSTT1041A-matched Placebo
  3. Drug: UTTR1147A
  4. Drug: UTTR1147A-matched Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Time to Recovery, Defined as the Time to a Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First)

Time: Day 28

Secondary Outcomes

Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

Time: From Baseline up to 28 days

Measure: Time to Hospital Discharge or "Ready for Discharge"

Time: Up to 28 days

Measure: Duration of Supplemental Oxygen

Time: Up to 28 days

Measure: Percentage of Participants Alive and Free of Respiratory Failure

Time: Day 28

Measure: Clinical Status, Assessed Using a 7-Category Ordinal Scale

Time: Days 14 and 28

Measure: Incidence of Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)

Time: Up to 28 days

Measure: Ventilator-Free Days

Time: Up to 28 days

Measure: Incidence of Intensive Care Unit (ICU) Stay

Time: Up to 28 days

Measure: Duration of ICU Stay

Time: Up to 28 days

Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First)

Time: Up to 28 days

Measure: Mortality Rate at Days 14 and 28

Time: Days 14 and 28

Measure: Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) of ≤2 Maintained for 24 hours

Time: Up to 28 days

Measure: Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

Time: Up to 60 days

Measure: Change from Baseline in Respiratory Rate

Time: From Baseline up to 60 days

Measure: Change from Baseline in Pulse Rate

Time: From Baseline up to 60 days

Measure: Change from Baseline in Systolic Blood Pressure

Time: From Baseline up to 60 days

Measure: Change from Baseline in Diastolic Blood Pressure

Time: From Baseline up to 60 days

Measure: Change from Baseline in Body Temperature

Time: From Baseline up to 60 days

Measure: Change from Baseline in Oxygen Saturation

Time: From Baseline up to 60 days

Measure: Change from Baseline in RR, QRS, PR, QT, and QTcF Intervals, as Measured by Electrocardiogram (ECG)

Time: From Baseline up to 60 days

Measure: Change from Baseline in Heart Rate, as Measured by Electrocardiogram (ECG)

Time: From Baseline up to 60 days

Measure: Number of Participants with Clinical Laboratory Test Abnormalities in Hematology Parameters

Time: From Baseline up to 60 days

Measure: Number of Participants with Clinical Laboratory Test Abnormalities in Blood Chemistry Parameters

Time: From Baseline up to 60 days

Measure: Serum Concentration of UTTR1147A at Specified Timepoints

Time: At predefined timepoints from Baseline until Study Completion (up to 60 days)

Measure: Serum Concentration of MSTT1041A at Specified Timepoints

Time: At predefined timepoints from Baseline until Study Completion (up to 60 days)

Measure: Prevalence of Anti-Drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study

Time: From Baseline up to 60 days
177 Major Determinants of COVID-19 Associated Pneumonia

Molecular testing (e.g PCR) of respiratory tract samples is the recommended method for the identification and laboratory confirmation of COVID-19 cases. Recent evidence reported that the diagnostic accuracy of many of the available RT-PCR tests for detecting SARS-CoV2 may be lower than optimal. Of course, the economical and clinical implications of diagnostic errors are of foremost significance and in case of infectious outbreaks, namely pandemics, the repercussions are amplified. False positives and false-negative results may jeopardize the health of a single patient and may affect the efficacy of containment of the outbreak and of public health policies. In particular, false-negative results contribute to the ongoing of the infection causing further spread of the virus within the community, masking also other potentially infected people.

NCT04387799
Conditions
  1. Pneumonia, Viral
  2. Pneumonia, Bacterial
  3. Coronavirus Infection
  4. Obstructive Lung Disease
Interventions
  1. Diagnostic Test: Serology for Covid-19
MeSH:Pneumonia, Bacterial Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Lung Diseases Lung Diseases, Obstructive
HPO:Abnormal lung morphology Pneumonia Pulmonary obstruction

Primary Outcomes

Description: assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.

Measure: Serology

Time: 3 weeks

Secondary Outcomes

Description: to find if the combination of CT scan and serology could help us in the identification of those patients who were initially negative at laboratory testing alone.

Measure: Efficacy of CT scan and Serology

Time: 3 weeks

Description: the efficacy of different pharmaceutical treatments against Covid-19

Measure: Efficacy of different pharmaceutical treatments

Time: 3 weeks
178 Study of the Prevalence of Deep Vein Thrombosis in Patients Hospitalized in Intensive Care for Acute Respiratory Failure Linked to Pneumonia Documented With SARS-COV2

Coronavirus 2 (SARS-CoV2) has been identified as the pathogen responsible for severe acute respiratory syndrome associated with severe inflammatory syndrome and pneumonia (COVID-19). Haemostasis abnormalities have been shown to be associated with a poor prognosis in these patients with this pneumonia. In a Chinese series of 183 patients, the hemostasis balance including thrombin time, fibrinogenemia, fibrin degradation products and antithrombin III were within normal limits. Only the D-Dimer assay was positive in the whole cohort with an average rate of 0.66 µg / mL (normal <50 µg / mL). These hemostasis parameters were abnormal mainly in patients who died during their management; the levels of D-dimers and fibrin degradation products were significantly higher while the antithrombin III was reduced. The findings on the particular elevation of D-dimers in deceased patients as well as the significant increase in thrombin time were also reported in another series. Higher numbers of pulmonary embolisms have been reported in patients with severe form of SARS-COV2 (data in press). This research is based on the hypothesis that the existence of deep vein thrombosis (DVT) could make it possible to screen patients at risk of pulmonary embolism and to set up a curative anticoagulation. The main objective is to describe the prevalence of deep vein thrombosis in patients hospitalized in intensive care for acute respiratory failure linked to documented SARS-COV2 pneumonia, within 24 hours of their admission.

NCT04388657
Conditions
  1. COVID
  2. Embolism and Thrombosis
  3. Pneumonia, Viral
Interventions
  1. Diagnostic Test: Echo-Doppler
MeSH:Pneumonia, Viral Pneumonia Thrombosis Embolism Embolism and Thrombosis
HPO:Pneumonia Thromboembolism

Primary Outcomes

Description: The primary outcome measure will be the percentage of patients with one or more DVTs from a lower extremity ultrasound scan.

Measure: percentage of patients with one or more DVTs.

Time: 28 days
179 Aerosol Inhalation of the Exosomes Derived From Allogenic COVID-19 T Cell in the Treatment of Early Stage Novel Coronavirus Pneumonia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused mass mortality in the last 3 months that necessitates urgent development of new therapeutical agents. So far there is no effective anti-viral drug to reduce viral load that has critical importance to prevent progress into severe viral pneumonia and systemic hyper inflammation state. This project is to offer a biologic agent based on T cell derived exosomes. This is a novel approach using our proprietary protocols for drug development. This clinical trial is to test the safety and efficacy of this new agent following targeted delivery by metered dose inhaler. The project have received proper approvals from the Turkish Ministry of Health and Erciyes University, Kayseri Turkey. Turk-Patent Application Number: PCT/TR2020/050302

NCT04389385
Conditions
  1. Corona Virus Infection
  2. Pneumonia
Interventions
  1. Biological: COVID-19 Specific T Cell derived exosomes (CSTC-Exo)
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Safety Assessment

Measure: Adverse reaction (AE) and severe AE (SAE)

Time: 28 days

Description: Time to Clinical Recovery (TTCR)

Measure: Efficacy Assessment

Time: 28 days

Description: Efficacy Assessment

Measure: The Rate of Recovery Without Mechanical Ventilator

Time: 28 days
180 TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial

Multifocal interstitial pneumonia represents the most common cause of admission in intensive care units and death in SARS-CoV2 infections. In our Hospital, similarly to what reported in literature, up to 25% of admitted patients with pneumonitis requires mechanical ventilation or oro-tracheal intubation within 5-10 days. No established treatment is available for this condition. Preliminary evidence is accumulating about the efficacy of an aggressive treatment of the corona virus-induced inflammation and, in particular, investigators believe that blocking JAK1 is clinically rewarding in down-regulating IL-6 driven inflammation in patients with corona-virus infection. Thus, investigators designed a randomized controlled trial to test the hypothesis that adding Tofacitinib to the standard treatment in the early phase of COVID related pneumonitis could prevent the development of severe respiratory failure needing mechanical ventilation.

NCT04390061
Conditions
  1. Pneumonitis, Interstitial
  2. COVID-19
Interventions
  1. Drug: Tofacitinib
  2. Drug: Hydroxychloroquine
MeSH:Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150

Measure: Prevention of severe Respiratory Failure requiring mechanical ventilation

Time: 14 days

Secondary Outcomes

Description: Rate of patients needing admission to the intensive care unit

Measure: Prevention of need of ICU admission

Time: 28 days

Description: Rate of patients who die due to COVID-19 related conditions

Measure: Prevention of COVID-19 related Deaths

Time: 28 days

Description: Role of some clinical and laboratory factors in predicting outcome (Age, sex, smoking status, Body Mass Index (BMI), Comorbidities (Diabetes, number of comorbidities), Respiratory Failure at admission defined as PaO2/FiO2<300, Extension of Ct-scan involvement, basal level of serum IL-6, vW-Factor, Thrombomodulin, KL-6, sACE2 and SP-D )

Measure: Identification of predictors of outcome

Time: 14 days

Description: Rate of severe drug-related adverse events

Measure: Incidence of Treatment-Emergent Adverse Events

Time: 28 days
181 A Phase 2 Study to Evaluate LB1148 for the Treatment of Pulmonary Dysfunction Associated With COVID-19 Pneumonia

This is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.

NCT04390217
Conditions
  1. COVID-19
  2. Coronavirus Disease 2019
  3. Covid19
  4. COVID-19 Pneumonia
Interventions
  1. Drug: LB1148
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The proportion of subjects alive and free of respiratory failure at Day 28.

Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure.

Time: 28 Days

Secondary Outcomes

Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)

Measure: Clinical status at fixed time points

Time: Measured at 3, 5, 7, 8, 10, 14 and 28 Days

Description: Length of hospital stay (live discharge)

Measure: Duration of hospital stay

Time: 28 Days

Description: Number and proportion of patients requiring admission to the intensive care unit

Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization

Time: 28 Days

Description: Length of ICU stay

Measure: Duration of ICU stay

Time: 28 Days

Description: Number and proportion of patients requiring invasive mechanical ventilation

Measure: Invasive mechanical ventilation requirements

Time: 28 Days

Description: Length of time patients require invasive mechanical ventilation

Measure: Duration of invasive mechanical ventilation

Time: 28 Days

Description: The number and proportion of patients deceased at Day 28

Measure: All-cause 28-day mortality

Time: 28 Days

Description: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

Measure: Safety and tolerability of LB1148

Time: 28 Days
182 What is the Effect of Mesenchymal Stem Cell Therapy on Seriously Ill Patients With Covid 19 in Intensive Care? (Prospective Double Controlled Study)

This study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery.

NCT04392778
Conditions
  1. Covid19
  2. Pneumonia
  3. Multiple Organ Failure
  4. Corona Virus Infection
Interventions
  1. Biological: MSC Treatment
  2. Biological: Saline Control
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Multiple Organ Failure
HPO:Pneumonia

Primary Outcomes

Description: Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)

Measure: Clinical improvement

Time: 3 months

Secondary Outcomes

Description: Improvement of lungs assessed by CT Scan

Measure: Lung damage improvement

Time: 3 months

Description: Negative, measured by RT-PCR laboratory tests for the virus

Measure: Sars-Cov-2 viral infection laboratory test

Time: 3 months

Description: Cell types and numbers

Measure: Blood test

Time: 3 months
183 BARICIVID-19 STUDY: MultiCentre, Randomised, Phase IIa Clinical Trial Evaluating Efficacy and Tolerability of Baricitinib as add-on Treatment of In-patients With COVID-19 Compared to Standard Therapy

There is urgent need of an effective therapy for Covid-19. To date, the best treatment of SARS-CoV-2 infection is unknown. Baricitinib has been identified as potential treatment for 2019-nCoV acute respiratory disease, because of its immunomodulating and hypothesized antiviral activity. This is a multicenter randomized clinical trial that aims to evaluate the efficacy and safety of baricitinib in patients with SARS-CoV2 pneumonia. Patients will be randomized to receive or not baricitinib as adjunctive therapy. All patients will continue to receive the ongoing standard therapy: chloroquine/idrossichloroquine and low-molecular weight heparin (LMWH) eventually associated with ritonavir/lopinavir or darunavir/ritonavir will be allowed for all included patients. The primary endpoint measure is the efficacy of baricitinib in reducing the number of patients requiring invasive ventilation after 7 and 14 days of treatment. Secondary endpoints will be mortality rates and toxicity of baricitinib.

NCT04393051
Conditions
  1. Covid-19
  2. SARS-CoV 2
  3. SARS Pneumonia
Interventions
  1. Drug: Baricitinib Oral Tablet
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Reduction of the number of patients requiring invasive ventilation

Measure: Need of invasive mechanical ventilation

Time: after 7 and 14 days of treatment

Secondary Outcomes

Description: Proportion of any cause deaths

Measure: Mortality

Time: 14- and 28-days from randomization

Description: Days from randomization to invasive mechanical ventilation

Measure: Time to invasive mechanical ventilation

Time: 30 days

Description: Days from randomization to independence from non-invasive mechanical ventilation

Measure: Time to independence from non-invasive mechanical ventilation

Time: 30 days

Description: Days from randomization to independence from oxygen therapy

Measure: Time to independence from oxygen therapy

Time: 30 days

Description: Days from randomization to improvement in oxygenation for at least 48 hours

Measure: Time to improvement in oxygenation for at least 48 hours

Time: 30 days

Description: Days of hospital stay

Measure: Length of hospital stay

Time: 30 days

Description: Days of ICU stay

Measure: Length of ICU stay

Time: 30 days

Description: Changes in pulmonary echography

Measure: Instrumental response

Time: 30 days

Description: Rate of adverse events codified by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0

Measure: Proportion of adverse events

Time: 30 days
184 Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia

In this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.

NCT04393948
Conditions
  1. SARS-CoV 2
Interventions
  1. Radiation: Phase 1
  2. Radiation: Phase 1
  3. Radiation: Phase 2
  4. Radiation: Phase 2
  5. Radiation: Phase 2
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Subjects will be treated with 100 cGy irradiation to a single (right-sided) lung (dose level 1) or 100 cGy irradiation to both lungs (dose level 2) following a 3 + 3 dose escalation scheme

Measure: Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation

Time: 4 days after randomization

Description: The ordinal scale is an assessment of the clinical status on a given day. Each day, the worst (lowest) score from the previous day will be recorded as the score for that previous day. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring low flow supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care Not hospitalized

Measure: Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization

Time: 4 days after randomization

Secondary Outcomes

Measure: Improvement or worsening on the 7-point ordinal scale over additional intervals

Time: Up to 30 days after randomization

Measure: Rate and duration of use of supplemental oxygen

Time: Up to 30 days after randomization

Measure: Rate and duration of fever > 38ºC

Time: Up to 30 days after randomization

Measure: Rate and duration of invasive mechanical ventilation

Time: Up to 30 days after randomization

Measure: Duration of hospitalization

Time: Up to 30 days after randomization

Measure: Proportion of participants with overall survival up to 30 days after randomization

Time: Up to 30 days after randomization

Measure: Improvement in radiographic findings related to infection/inflammation; comparisons include on study versus baseline scans and irradiated vs. unirradiated lung in subjects randomized to receive single lung irradiation

Time: Up to 30 days after randomization

Measure: Treatment-emergent adverse events

Time: Up to 30 days after randomization
185 COVID-19 Imaging Features

The novel coronavirus SARS-CoV2 clinically presents with pneumonia, characterised by fever, cough, dyspnea. The severity of the disease varies widely with evidence of mild disease in the majority of confirmed cases, severe pneumonia-dyspnea, hypoxia or lung involvement at imaging within 24-48 hours- and critical disease with respiratory failure, shock or multi-organ failure in particular patient cohorts. Imaging plays a key role is diagnosis and progression of this disease.

NCT04394026
Conditions
  1. Viral Pneumonia
  2. COVID
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluate RX imaging aspects at the time of diagnosis and until discharge.

Measure: Describe qualitative and quantitative variables

Time: Through study completion, an average of 5 months

Description: Evaluate CT imaging aspects at the time of diagnosis and until discharge.

Measure: Describe qualitative and quantitative variables

Time: Through study completion, an average of 5 months

Description: Correlate imaging findings to OS

Measure: Ability of imaging to predict disease progression

Time: Through study completion, an average of 5 months

Description: Correlate imaging findings over time

Measure: Ability of imaging to predict disease evolution

Time: Through study completion, an average of 5 months

Secondary Outcomes

Description: Correlate imaging findings to age and sex

Measure: Imaging findings and demographic data

Time: Through study completion, an average of 5 months

Description: Correlate imaging findings to laboratory values

Measure: Imaging findings and laboratory exams

Time: Through study completion, an average of 5 months
186 Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers

The host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.

NCT04394182
Conditions
  1. Pneumonia, Viral
  2. Cytokine Storm
Interventions
  1. Radiation: Ultra-Low-dose radiotherapy
  2. Device: ventilatory support with oxygen therapy
  3. Drug: Lopinavir/ritonavir
  4. Drug: Hydroxychloroquine
  5. Drug: Azithromycin
  6. Drug: Piperacillin/tazobactam
  7. Drug: Low molecular weight heparin
  8. Drug: Corticosteroid injection
  9. Drug: Tocilizumab
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

Measure: Oxygen Therapy Status at Day 2

Time: At 2 after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2

Time: At 2 days after RT

Secondary Outcomes

Description: Pa02 / Fi02 > 300 mmHg

Measure: Blood Gas Analysis at Day 2

Time: At 2 days after RT

Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

Measure: Blood Test at Day 2

Time: At 2 days after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

Measure: Oxygen Therapy Status at Day 5

Time: At 5 after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5

Time: At 5 days after RT

Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

Measure: Blood Test at Day 5

Time: At 5 days after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

Measure: Oxygen Therapy Status at Day 7

Time: At 7 after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7

Time: At 7 days after RT

Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

Measure: Blood Test at Day 7

Time: At 7 days after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7

Time: At 7 days after RT

Description: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)

Measure: Recovery time

Time: From RT administration until hospital discharge or death

Description: COVID-19 negativization test

Measure: COVID-19 status

Time: At 7 days after RT

Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1

Time: At 1 month after RT

Description: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.

Measure: Acute Toxicity

Time: 1-3 months after RT
187 Trial of Silymarin in Adults With COVID-19 Pneumonia

A randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects

NCT04394208
Conditions
  1. COVID-19
  2. Viral Pneumonia Human Coronavirus
Interventions
  1. Drug: Silymarin
  2. Drug: Placebo
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.

Measure: Time to clinical improvement

Time: 7-28 days

Secondary Outcomes

Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14

Measure: Clinical outcome

Time: 7-14 days

Description: Time in days patient was intubated

Measure: Duration of Mechanical Ventilation

Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

Description: Total days of hospitalization

Measure: Hospitalization

Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

Description: number of days patient remained with positive RT-PCR SARS-CoV-2 swab

Measure: Virologic Response

Time: Randomization till discharge, up to 28 days

Description: Any adverse events whether related to medication or not

Measure: Adverse events

Time: Randomization till hospital discharge, up to 28 days
188 Low Dose Radiation Therapy for Covid-19 Pneumonia: A Pilot Study

Radiotherapy in low doses (30 to 100 cGy) was a popular treatment of viral pneumonias until 1940s. Low dose radiation therapy (LDRT) could possibly reduce the inflammation and prevent the cytokine storm thus mitigating the severity of pneumonitis. This is a single arm study designed to assess the feasibility and clinical efficacy of low dose radiation therapy (70 cGy in single fraction) in the patients with COVID-19 pneumonia. A total of 10 eligible patients (as per inclusion criteria) will be recruited and response will be assessed based on the symptomatic improvement or deterioration by using the National Early Warning Score (NEWS). The NEWS score will be recorded on baseline and then on Day 3, Day 7 and Day 14.

NCT04394793
Conditions
  1. COVID-19
  2. Pneumonia
Interventions
  1. Radiation: Low dose radiation therapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: NEWS score

Measure: Symptomatic improvement by National Early warning score (NEWS)

Time: Day 3

Description: NEWS score

Measure: Symptomatic improvement by National Early warning score (NEWS)

Time: Day 7

Description: NEWS score

Measure: Symptomatic improvement by National Early warning score (NEWS)

Time: Day 14

Description: Days

Measure: Length of hospital stay

Time: 30 days or date of death whichever is earlier

Description: Number of patients

Measure: Number of ICU admissions or deaths

Time: 30 days
189 A Phase I Study of ResCure™ to Treat COVID-19 Infection

This is a Phase I open-label interventional study which will test the efficacy of ResCure™ in the treatment of patients with COVID-19 infection.

NCT04395716
Conditions
  1. COVID
  2. Covid-19
  3. Corona Virus Infection
  4. Sars-CoV2
  5. Coronavirus-19
  6. SARS Pneumonia
  7. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
Interventions
  1. Biological: ResCure™
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR

Measure: The rate of recovery of mild or moderate COVID-19 in patients using ResCure™

Time: 12 Weeks

Description: Reduction and/or progression of symptomatic days, reduction of symptom severity

Measure: Reduction or progression of symptomatic days

Time: 12 Weeks

Description: Pulse from baseline to 12 weeks

Measure: Assess the safety of ResCure™ via pulse

Time: 12 Weeks

Description: Oxygen saturation from baseline to 12 weeks

Measure: Assess the safety of ResCure™ via oxygen saturation

Time: 12 Weeks

Description: EKG from baseline to 12 weeks

Measure: Assess the safety of ResCure™ via EKG

Time: 12 Weeks

Description: Assess Adverse Events and Serious Adverse Events due to ResCure™

Measure: Assess Tolerability of ResCure™

Time: 12 Weeks
190 A Study to Collect Bone Marrow for Process Development and Production of Bone Marrow Mesenchymal Stromal Cells to Treat Severe COVID19 Pneumonitis

The COVID-19 pandemic, commonly referred to as "coronavirus", first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body's respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment. While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as "pneumonitis"). This inflammation is thought to be caused by their body's immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive. Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation.

NCT04397471
Conditions
  1. Healthy Volunteers for Bone Marrow Donation
Interventions
  1. Procedure: Bone Marrow Harvest
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Successful identification of healthy volunteers in acceptable timeframe (i.e. within days) to donate bone marrow.

Measure: Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe.

Time: 3 or more participants recruited in 1 month

Description: Successful manufacture of bone marrow-mesenchymal stromal cells suitable for clinical use

Measure: Manufacture a cell-based product suitable for clinical use

Time: Successfully opening the next phase of the trial in approx. 2 months

Secondary Outcomes

Description: Ability to prepare a dossier acceptable to the MHRA. Success will achieved if the dossier is deemed acceptable.

Measure: Establishment of a robust process of production

Time: Successfully opening the next phase of the trial in approx. 2 months

Description: Successful manufacturing of products will be defined initially as the award of a Manufacturers Specials Licence to the CCTL to allow the manufacture of Bone Marrow-Mesenchymal Stromal Cells for compassionate use.

Measure: Production of stability data to be used in the MHRA dossier for the COMET clinical trial.

Time: Successfully opening the next phase of the trial in approx. 2 months

Description: Successful manufacturing of products will be subsequently defined by production under MA(IMP) licence, allowing for future production under CTIMP and CTA.

Measure: Production of cell-based products to be administered to COVID-19 patients with severe pneumonitis.

Time: Successfully opening the next phase of the trial in approx. 2 months

Description: Successful manufacturing of products, under MA(IMP) licence will be defined as the availability of Bone Marrow-Mesenchymal Stromal Cells to be used in the context of the COMET20 clinical trial.

Measure: Analysis of cells for understanding production, manufacture and related research.

Time: Successfully opening the next phase of the trial in approx. 2 months
191 A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial)

This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.

NCT04397497
Conditions
  1. Covid-19
  2. Acute Respiratory Failure
  3. ARDS, Human
  4. Sars-CoV2
  5. Viral Pneumonia
Interventions
  1. Drug: Mavrilimumab
  2. Drug: Placebo
MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm

Measure: Reduction in the dependency on oxygen supplementation

Time: within day 14 of treatment

Secondary Outcomes

Description: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

Measure: Proportion of responders (using the WHO 7-point ordinal scale)

Time: Day 7, 14, and 28

Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

Measure: Time to response (using the WHO 7-point ordinal scale)

Time: Within day 28 of intervention

Description: Proportion of patients with at least two-point improvement in clinical status

Measure: Proportion of improving patients (using the WHO 7-point ordinal scale)

Time: At day 7, 14, and 28

Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner

Measure: Time to resolution of fever

Time: Within day 28 of intervention

Description: COVID-19-related death

Measure: Reduction in case fatality

Time: Within day 28 of intervention

Description: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)

Measure: Proportion of patient requiring mechanical ventilation/deaths

Time: Within day 14 of intervention

Description: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)

Measure: Change in biochemical markers

Time: Within day 28 of intervention or discharge -whatever comes first

Description: Median changes of NEWS2 score from baseline

Measure: Median changes in the National Early Warning Score 2 (NEWS2)

Time: At day 7, 14, and 28

Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)

Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2)

Time: Within day 28 of intervention or discharge -whatever comes first

Description: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.

Measure: Variations in radiological findings

Time: Within day 28 of intervention or discharge -whatever comes first

Description: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: By day 84

Other Outcomes

Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg

Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity

Time: Within day 28 of intervention

Description: Median changes in serum IL-6

Measure: Changes in serum IL-6 (exploratory biomarker)

Time: By day 84

Description: Median changes in serum IL-1 receptor antagonist

Measure: Changes in serum IL-1RA (exploratory biomarker)

Time: By day 84

Description: Median changes in serum TNF-alpha

Measure: Changes in serum TNF-alpha (exploratory biomarker)

Time: By day 84

Description: Median variations in haemoglobin and leucocyte counts

Measure: Changes in CBC + differential (exploratory biomarker)

Time: By day 84

Description: Median titres od anti-SARS-CoV2 antibodies

Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker)

Time: By day 84

Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR

Measure: Virus eradication (exploratory biomarker)

Time: By day 84

Description: Proportion of patients who developed anti-drug antibodies

Measure: Anti-drug antibodies (exploratory biomarker)

Time: By day 84
192 Inhaled NO for the Treatment of COVID-19 Caused by SARS-CoV-2 (US Trial)

The purpose of this open label, randomized, study is to obtain information on the safety and efficacy of 80 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.

NCT04397692
Conditions
  1. Corona Virus Infection
  2. COVID-19
  3. SARS-CoV 2
  4. Nitric Oxide
  5. Respiratory Disease
  6. Pneumonia, Viral
  7. Inhaled Nitric Oxide
Interventions
  1. Device: Nitric Oxide delivered via LungFit™ system
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Aspiration Respiration Disord Respiration Disorders Respiratory Tract Diseases
HPO:Pneumonia

Primary Outcomes

Description: Time to deterioration measured by need for NIV, HFNC or intubation

Measure: Time to deterioration

Time: 14 Days

Secondary Outcomes

Description: Time to non-invasive ventilation

Measure: Time to NIV

Time: 14 Days

Description: Time to high flow nasal cannula

Measure: Time to HFNC

Time: 14 Days

Description: Time to intubation

Measure: Time to intubation

Time: 14 days

Description: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

Measure: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

Time: 14 days

Other Outcomes

Description: Need for supplemental oxygen

Measure: Need for supplemental oxygen

Time: 14 days

Description: Change in viral load

Measure: Change in viral load

Time: 30 days

Description: Duration of the Hospital Length of Stay (LOS)

Measure: Duration of the Hospital Length of Stay (LOS)

Time: 14 days

Description: Mortality rate at Day 30

Measure: Mortality rate at Day 30

Time: 30 days
193 An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants With COVID-19 Pneumonia Caused by SARS-CoV-2.

The purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.

NCT04397757
Conditions
  1. COVID-19
Interventions
  1. Biological: COVID-19 Convalescent Plasma
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Cumulative incidence of serious adverse events (SAEs) at Study Day 29.

Measure: Participants with serious adverse events.

Time: Up to 29 days from treatment

Description: Severity is measured by the 8-point ordinal clinical severity scale at D29 where 1 is the best state to be in and 8 is the worst (equals death).

Measure: Comparison of clinical severity score between patients on the experimental versus control arms;

Time: Up to 29 days from treatment

Secondary Outcomes

Description: Time to recovery, defined by time to levels 1-3 on the ordinal scale

Measure: Clinical status assessment, using 8-point ordinal scale, of convalescent plasma administration by comparing treatment vs control arms

Time: Up to 29 days from treatment

Description: Time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first.

Measure: Clinical status assessment using the National Early Warning Score (NEWS) of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment, daily while hospitalized until discharge or death and on Days 15 and 29.

Description: Oxygen-free days to Day 29.

Measure: Oxygen-free days of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29

Description: Incidence of new oxygenation use up to Day 29.

Measure: Incidence of new oxygenation use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Days of new oxygen use up to Day 29.

Measure: Duration of new oxygen use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Days of non-invasive ventilation/high flow oxygen up to Day 29

Measure: Non-invasive ventilation/high flow oxygen days up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Incidence of non-invasive ventilation up to Day 29.

Measure: Incidence of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Days of non-invasive ventilation/high flow oxygen up to Day 29

Measure: Duration of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Ventilation/ECMO free days up to Day 29. mechanical ventilation or ECMO use during the study.

Measure: Ventilator/ECMO free days to Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Incidence of new mechanical ventilation or ECMO use up to Day 29.

Measure: Incidence of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Days of new mechanical ventilation or ECMO use up to Day 29.

Measure: Duration of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms

Time: From enrollment to Day 29.

Description: Duration of hospitalization.

Measure: Duration of hospitalization of convalescent plasma administration by comparing treatment vs control arms

Time: To Day 29

Description: D14 and D28 mortality.

Measure: Mortality of convalescent plasma administration by comparing treatment vs control arms

Time: To Day 28

Description: Cumulative incidence of SAEs through Day 29.

Measure: Cumulative incidence of SAEs through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29

Description: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29.

Measure: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29

Description: Changes in WBC with differential on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in WBC with differential through day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29

Description: Changes in hemoglobin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in hemoglobin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29

Description: Changes in platelets measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in platelets measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29.

Description: Changes in creatinine measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in creatinine measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29.

Description: Changes in glucose measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in glucose measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29.

Description: Changes in bilirubin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in bilirubin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29

Description: Changes in ALT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in ALT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29

Description: Changes in AST measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in AST measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29.

Description: Changes in PT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

Measure: Changes in PT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

Time: Through Day 29.
194 A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia

The primary objective of this study is determine the safety and efficacy of ACT-20-MSC (allogenic human umbilical derived mesenchymal stem cells) and ACT-20-CM (allogenic human umbilical derived mesenchymal stem cells in conditioned media) in patients with moderate to severe COVID-19 pneumonia.

NCT04398303
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Biological: ACT-20-MSC
  2. Biological: ACT-20-CM
  3. Biological: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Mortality at day 30

Time: 30 days post treatment

Secondary Outcomes

Description: Number of ventilator-free days

Measure: Ventilated Subjects - Ventilator Free Days

Time: 28 days post treatment

Description: Improvement in ventilator settings: Minute ventilation, PEEP, FiO2

Measure: Ventilated Subjects - Improvement in Ventilator Settings

Time: 28 days post treatment, or until off of ventilator

Description: Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration.

Measure: High-Flow O2 Support Subjects - Step-Down O2 Therapy

Time: 30 days post treatment, or until off of high-flow O2 support

Description: Respiration Rate < 30 for > 24 hours.

Measure: High Flow O2 Support Subjects - Respiration Rate

Time: 30 days post treatment, or until off of high-flow O2 support

Description: Number of ICU-free days

Measure: Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days

Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

Description: Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation

Measure: Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement

Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

Description: Increased Berlin Criteria score > 24 hours

Measure: Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score

Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
195 The Utility of Bedside Lung Ultrasonography on Diagnosis of COVID-19 at Emergency Department

Novel Coronavirus 2019 Disease (COVID-19) mortality is highly associated with viral pneumonia and its complications. Accurate and prompt diagnosis shown to be effective to improve outcome by providing early treatment strategies. While chest X-ray (CXR) and computerized tomography (CT) are defined as gold standard, given the advantage of being an ionized radiation free, practical technique point of care ultrasound (POCUS) is also reported as a diagnostic tool for COVID-19. There are limited studies regarding the importance of POCUS in diagnosis and review of COVID-19. Therefore the aim of this study is to evaluate the utility of bedside lung ultrasound on diagnosis of COVID-19 for patients admitted to emergency department .

NCT04399681
Conditions
  1. COVID
  2. Pneumonia, Viral
Interventions
  1. Device: Bedside lung ultrasound
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Efficacy of POCUS on diagnosis of viral pneumonia caused by COVID 19

Measure: Presence of viral pneumonia caused by COVID 19

Time: 3 months
196 A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia

The objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia. This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.

NCT04399798
Conditions
  1. Corona Virus Infection
Interventions
  1. Drug: Baricitinib
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)

Time: 8 days

Description: Absence of death within 8 days from enrollment

Measure: Response to treatment: survival

Time: 8 days

Secondary Outcomes

Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days

Time: 8 days

Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days

Time: 15 days

Description: To quantify mortality within 8 and 15 days

Measure: Mortality

Time: 8 days and 15 days

Description: SpO2 will be assessed with the median and 25th-75th percentiles

Measure: Peripheral capillary oxygen saturation (SpO2)

Time: 8 days; 15 days

Description: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles

Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

Time: 8 days; 15 days

Description: Number of patients over the number of patients enrolled

Measure: To assess the rate of patients admitted to the intensive care unit

Time: 8 days; 15 days

Description: Median number of days and 25th-75th percentiles

Measure: To measure the length of hospital stay

Time: 8 days; 15 days

Description: To quantify 28-day mortality

Measure: 28-day mortality

Time: 28 days

Description: Number of patients readmitted over the number patients enrolled

Measure: To quantify the rate of re-admission within 28 days

Time: 28 days

Description: Number, type, and severity of adverse events

Measure: To quantify the cumulative incidence and severity of adverse events

Time: 28 days

Description: Serial serum assessments from baseline up to 15 days

Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;

Time: 15 days

Description: Serial serum assessments from baseline up to 15 days

Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels

Time: 15 days

Description: Serial assessments from baseline up to 15 days for viral load persistence

Measure: Viral load analyses

Time: 15 days
197 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation

The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

NCT04399980
Conditions
  1. COVID 19
  2. SARS-CoV 2
  3. Pneumonia
Interventions
  1. Drug: Mavrilimumab
  2. Drug: Placebos
MeSH:Pneumonia Respiratory Insufficiency Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Number of subjects alive and off of oxygen

Measure: Proportion of subjects alive and off of oxygen at day 14

Time: Day 14

Secondary Outcomes

Description: Number of subjects that are alive

Measure: Proportion of subjects alive at 28 days

Time: Day 28

Description: Number of subjects alive and without respiratory failure

Measure: Proportion of subjects alive and without respiratory failure at 28 days

Time: Day 28
198 Multiparametric Evaluation of One-year Outcomes in Survivors of the Severe COVID-19 Pneumonia After Intensive Care Unit

Pneumonia caused by infection at SARS-CoV2 may be complicated by an acute respiratory detress syndrome need to take care in intensive care unit and can lead to mechanical ventilation. COVID-19 is a pandemic disease and lot of patients will survive of severe pneumoniae at SARS-CoV2 treat in ICU. At this time, there is no data about functional prognosis at long term. This aim of this study is to evaluate the recovery of quality of life, respiratory function, neuromuscular function at long term and incidence of post-traumatic stress disorder. Patients will follow during 1year after out of ICU with 3 consultations at 3month, 6month and 12month. At each consultation patients will be evaluated about respiratory function, effort tolerance via 6minutes walking test, psychologic function with IES-R and HAD score and quality of life with SF36. The hypothesis is that patients who survived of ARDS post infection at SARS-CoV2 have persistent functional limitation and alteration of quality of life one year after being discharged from the ICU.

NCT04401111
Conditions
  1. COVID
  2. ARDS
  3. Quality of Life
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The primary outcome is the score SF36 at 3month, 6month, 12 month after discharged of ICU in study population

Measure: Evaluation of recovery of quality of life in first year after ICU discharged in patients hospitalised for severe pneumonia at SARS-CoV2

Time: 1 year

Secondary Outcomes

Description: Evaluation of functional respiratory exploratory

Measure: Evaluation of respiratory function during first year after ICU discharged in population studied

Time: 1 year

Description: Mesure of the traveled distance in six-min walk test

Measure: Evaluation at 1 year of evolution of functional exercises capacity in population studied

Time: 1 year

Description: Mesure of creatinine clairance and proteinuria

Measure: Evaluation of evolution of renal function during first year after ICU discharged in population studied

Time: 1 year

Description: Sudy of cardiac ultrasonography parameters

Measure: Evaluation of evolution of right and left myocardic function during first year after ICU discharged in population studied

Time: 1 year

Description: Occurence of post-traumatic stress disorder or anxious and depressive disorders in population studied

Measure: Evaluation at 1 year of incidence of psychiatric pathology

Time: 1 year

Description: Rate of return to professional activity

Measure: Evaluation at 1 year of consequences in professional activity in population studied

Time: 1 year
199 Development and Validation of Predictive Models for Intensive Care Admission and Death of COVID-19 Patients in a Secondary Care Hospital in Belgium.

To build simple and reliable predictive scores for intensive care admissions and deaths in COVID19 patients. These scores adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guidelines. The outcomes of the study are (i) admission in the Intensive Care Unit admission and (ii) death. All patients admitted in the Emergency Department with a positive reverse transcription-polymerase chain reaction SARS-COV2 test were included in the study. Routine clinical and laboratory data were collected at their admission and during their stay. Chest X-Rays and CT-Scans were performed and analyzed by a senior radiologist. Generalized Linear Models using a binomial distribution with a logit link function (R software version X) were used to develop predictive scores for (i) admission to ICU among emergency ward patients; (ii) death among ICU patients. A first panel of Number Models with the highest AIC (BIC) was preselected. Ten-fold cross-validation was then used to estimate the out-of-sample prediction error among these preselected models. The one with the smallest prediction error was in the end singled out .

NCT04401228
Conditions
  1. COVID19
  2. Pneumonia, Viral
  3. Inflammatory Response
Interventions
  1. Other: predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables?
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: admission to ICU

Time: through study completion, an average of 1 year

Secondary Outcomes

Measure: death

Time: through study completion, an average of 1 year
200 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19

This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.

NCT04402866
Conditions
  1. Acute Lung Injury (ALI) Associated With COVID-19
  2. Lung Inflammation Associated With COVID-19
Interventions
  1. Drug: TD-0903
  2. Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Number of Respiratory Failure-Free Days (RFDs) from randomization through Day 28

Measure: Part 2: Respiratory Failure-Free Days (RFDs)

Time: Baseline through Day 28

Secondary Outcomes

Description: Proportion of subjects in each category of the 8-point Clinical Status scale. The Clinical Status scale contains 8 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized, no limitations on activities') to 8 (representing 'Death'). The various measures describe hospitalization status and the various limitations and requirements for oxygen support.

Measure: Part 2: Clinical Status Scale

Time: Day 7, 14, 21 and 28

Description: Proportion of subjects alive and respiratory failure-free on Day 28

Measure: Part 2: Subjects alive and respiratory failure-free

Time: Day 28

Description: Change from baseline in SaO2/FiO2 ratio on Day 7

Measure: Part 2: SaO2/FiO2 ratio

Time: Baseline, Day 7
201 Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 and Increased Inflammatory Markers: a Phase III Randomized Clinical Trial (COVID-19 Coalition Brazil VI) (TOCIBRAS)

The trial evaluates the efficacy and safety of Tocilizumab, which rapidly reduces the inflammation process through inhibition of IL-6 in patients with moderate to severe COVID-19 with increased inflammatory markers. There will be two arms in the trial, one receiving the best supportive care, and the other receiving it plus tocilizumab. Patients will be followed until Day 29 after randomization.

NCT04403685
Conditions
  1. COVID
  2. SARS Pneumonia
  3. Cytokine Release Syndrome
Interventions
  1. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of clinical status of patients on day 15 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)

Measure: Evaluation of clinical status

Time: Day 15 of the trial

Secondary Outcomes

Description: All-cause mortality from randomization to day 28

Measure: All-cause mortality

Time: 29 days after the randomization

Description: Deaths that occur during hospital admission.

Measure: Hospital Mortality

Time: 29 days after the randomization

Description: Improvement of SOFA scale of patients at day 8, 15 and 29 after randomization

Measure: Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale

Time: 29 days after the randomization (evaluations at D8 and D15)

Description: Evaluation of clinical status of patients on the day 8, 22 and 29 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)

Measure: Evaluation of clinical status

Time: 29 days after the randomization (evaluations at D8 and D29)

Description: Days alive and free from mechanical ventilation since randomization

Measure: Ventilator free days

Time: 29 days after the randomization

Description: Days from randomization to independence of oxygen support

Measure: Time until oxygen support independence

Time: 29 days after the randomization

Description: Number of patients that were not at mechanical ventilation at randomization and that required that support.

Measure: Need of mechanical ventilation support

Time: 29 days after the randomization

Description: Number of days to mechanical ventilation for patients that were not receiving it at randomization. For patients that were not in mechanical ventilation at randomization: number of days until that support was required.

Measure: Days to mechanical ventilation support.

Time: 29 days after the randomization

Description: Lenght of hospitalization stay in survivors (in days)

Measure: Duration of hospitalization

Time: 29 days after the randomization

Description: Incidence of other infections (aside from SARS-CoV 2)

Measure: Other infections

Time: 29 days after the randomization

Description: Incidence of thromboembolic events in patients with COVID-19

Measure: Incidence of thromboembolic events

Time: 29 days after the randomization

Description: Evaluation of adverse events, as well as serious and unexpected adverse events

Measure: Incidence of adverse events

Time: 29 days after the randomization (specific evaluations at D8, D15 and D29)

Other Outcomes

Description: Correlation of inflammatory tests and cytokines with clinical outcomes: clinical status (ordinal scale), time to oxygen support independence, ventilator free days, need of mechanical ventilation and mortality

Measure: Correlation of inflammatory tests and cytokines with clinical outcomes

Time: 29 days after the randomization

Description: Evaluation the kinetics of hemostasia exams, inflammatory tests, cytokines, flow cytometry of blood cells, CBC, renal and liver exams

Measure: Exploratory evaluation of laboratory exams during hospitalization

Time: 29 days after the randomization

Description: Evaluation of viral clearance of SARS-CoV2 using RT-PCR analysis of nasopharyngeal swab

Measure: Evaluation of viral clearance of SARS-CoV2

Time: Day 8 and 15 after randomization
202 CACOLAC : Randomized Trial of Citrulline Administration in the Hospital Patient in Intensive Care for COVID-19 Acute Respiratory Distress Syndrome

Respiratory involvement of SARS-CoV2 leads to acute respiratory distress syndrome (ARDS) and significant immunosuppression (lymphopenia) exposing patients to long ventilation duration and late mortality linked to the acquisition of nosocomial infections. Lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV2 infection may be linked to expansion of MDSCs and arginine depletion of lymphocytes. Severe forms of COVID-19 pneumonitis are marked by persistent ARDS with acquisition of nosocomial infections as well as by prolonged lymphocytic dysfunction associated with the emergence of MDSC. It has been found in intensive care patients hypoargininaemia, associated with the persistence of organ dysfunction (evaluated by the SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, the enteral administration of ARG was not deleterious and increased the synthesis of ornithine, suggesting a preferential use of ARG by the arginase route, without significant increase in argininaemia nor effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, is an interesting alternative to increase the availability of ARG. Recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. The hypothesis is therefore that CIT supplementation is more effective than the administration of ARG to correct hypoargininaemia, decrease lymphocyte dysfunction, correct immunosuppression and organ dysfunction in septic patients admitted to intensive care. The main objective is to show that, in patients hospitalized in intensive care for ARDS secondary to COVID-19 pneumonia, the group of patients receiving L-citrulline for 7 days, compared to the group receiving placebo, has a score of organ failure decreased on D7 (evaluated by the SOFA score) or by the last known SOFA score if the patient has died or been resuscitated.

NCT04404426
Conditions
  1. ARDS Secondary to COVID-19 Pneumonia
Interventions
  1. Dietary Supplement: L-citrulline
  2. Other: Placebo
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
HPO:Pneumonia

Primary Outcomes

Description: SOFA score for organ failures on D7 or last known SOFA score if the patient has died or been resuscitated

Measure: SOFA

Time: Day 7

Secondary Outcomes

Description: Number and phenotype of lymphocytes on days 1, 3, 7, 10 and 14

Measure: Number and phenotype of lymphocytes

Time: Days 1, 3, 7, 10 and 14

Description: Monocytic expression HLA-DR (Flow cytometry) on days 1, 3, 7, 10 and 14

Measure: HLA-DR

Time: Days 1, 3, 7, 10 and 14

Description: Number of Myeloid-derived suppressor cells (Flow cytometry) on days 1, 3, 7, 10 and 14

Measure: Number of Myeloid-derived suppressor cells

Time: Days 1, 3, 7, 10 and 14

Description: Plasma cytokines / chemokines (IL-6, IL-8, IL-10, IL-7, CXCL10, G-CSF, TNF-alpha, IFN-β) at days 1, 3, 7, 10 and 14

Measure: Plasma cytokines / chemokines

Time: Days 1, 3, 7, 10 and 14

Description: Diversity of the repertoire T at days 1, 3, 7, 10 and 14

Measure: Repertoire T

Time: Days 1, 3, 7, 10 and 14

Description: T lymphocyte exhaustion: measurement of lymphocyte apoptosis and lymphocyte proliferation on days 1, 3, 7, 10 and 14

Measure: Lymphocyte T exhaustion

Time: Days 1, 3, 7, 10 and 14

Description: Measurement of mitochondrial activity (measurement of the number of mitochondria and their membrane potential, measurement of the expression of Beclin1) on days 1, 3, 7, 10 and 14

Measure: Mitochondrial activity

Time: Days 1, 3, 7, 10 and 14

Description: Plasma amino acids (arginine and its metabolites (ornithine, glutamate, glutamine, citrulline, proline) and tryptophan / kynurenine) on days 1, 3, 7, 10 and 14

Measure: Plasma amino acids

Time: Days 1, 3, 7, 10 and 14

Description: SOFA score of organ failures on days 3, 7, 10 and 14

Measure: SOFA

Time: Days 3, 7, 10 and 14

Description: Duration of hospitalization in intensive care (days), up to day 28 maximum

Measure: Duration of hospitalization in intensive care

Time: Day 28

Description: Duration of hospital stay in hospital (days), up to day 28 maximum

Measure: Duration of hospital stay in hospital

Time: Day 28

Description: Duration of mechanical ventilation (days), up to day 28 maximum

Measure: Duration of mechanical ventilation

Time: Day 28

Description: Mortality in intensive care on day 28

Measure: Mortality in intensive care on day 28

Time: Day 28

Description: Hospital mortality on day 28

Measure: Hospital mortality on day 28

Time: Day 28

Description: Measurement of the presence of SARS-CoV2 in the tracheal aspiration by PCR on days 1, 3, 7, 10 and 14

Measure: Measurement of the presence of SARS-CoV2

Time: Days 1, 3, 7, 10 and 14

Description: Incidence of nosocomial infections during the intensive care unit (maximum D28). The diagnosis of nosocomial infections will be made according to the definitions of nosocomial infections of the CDC. An independent committee of experts will validate or not the infections

Measure: Nosocomial infections

Time: D28

Description: Number of days of exposure to each antibiotic per 1000 days of hospitalization (maximum day 28).

Measure: Number of days of exposure to each antibiotic per 1000 days of hospitalization

Time: Day 28
203 Plasma From Covalescent Donors With Covid-19 for the Management of Patients With SARS-COV-2 Fase II and III, a Doble Center Randomized Doble Blind Trial

The new SARS-CoV-2 coronavirus is an emerging virus originating in Wuhan, China that has spread rapidly throughout the world. As of March 24, 2020, China had reported 81,767 cases with 3,281 deaths, and the World Health Organization (WHO) declared coronavirus 19 (COVID-19) a pandemic. COVID-19 disease is currently a pandemic without specific therapeutic agents and substantial mortality. So it is of utmost importance to find new treatments. Various therapies, such as Remdesivir and Favipiravir, are being investigated but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was used as an empirical treatment during the Ebola virus outbreaks in 2014 and in 2015 a protocol was established for the treatment of the Middle East respiratory syndrome coronavirus (MERS) with convalescent plasma. This approach with other viral infections such as SARS-CoV, H5N1 avian influenza and H1N1 influenza suggesting that plasma transfusion from convalescent donors was effective. For this study, plasma from convalescent donors will be collected from those donors who have recovered from SARS-CoV-2 and are between 10 and 14 days after illness. Immunoassays will be carried out to detect total IgM and IgG antibodies against SARS-CoV-2. Patients will receive 1 to 3 convalescent plasma transfusions, depending on the response to treatment. The expected results are: normal body temperature, decrease in viral load or negative between 10-12 days after transfusion of convalescent plasma, which does not progress to ARDS, extubation of mechanical ventilation within two weeks of treatment, recovery of patient.

NCT04405310
Conditions
  1. SARS Pneumonia
Interventions
  1. Biological: Convalescent Plasma of patients with COVID-19
  2. Other: placebo (hartmann plus albumine)
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: any cause

Measure: Death

Time: 15 days

Secondary Outcomes

Description: Time for discharge from the ICU

Measure: Lenth of stay ICU

Time: 15 days

Description: Number of days with ventilatory support

Measure: Days of Mechanical Ventilation

Time: 15 days

Description: Number of days with need of oxigen suport without Mechanical Ventilation

Measure: Suplemental Oxigen support

Time: 15 days

Description: changes in viral load

Measure: Viral Load by RT-PCR

Time: 15 days

Description: changes in pro- inflamatory and anti-inflamatory biomarkes (IL-6, PCR, Ferritine, D Dimer, IL-8 IL-10

Measure: Inflamatory biomarkers

Time: 15 days

Description: changes in SOFA scale

Measure: SOFA (sequencial Organ Failure Assesment)

Time: 15 days
204 Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 Pneumonia: A Randomized,Open-label,Controlled Clinical Trial

This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia

NCT04405921
Conditions
  1. SARS-CoV-2 Pneumonia
  2. COVID-19
Interventions
  1. Drug: Hydroxychloroquine 200 Mg Oral Tablet
  2. Drug: Azithromycin 250 MG
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19.

Measure: Clinical recovery at day-14, from the start of treatment.

Time: 14 days

Secondary Outcomes

Description: RT-PCR will be realized in same laboratory

Measure: Viral Clearance via RT-PCR at day 5- 7-10 and day 14

Time: 5- 7-10 and day 14
205 Clinical Scores for Outcome Prediction in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation - a Retrospective Multi-center Registry Study

The prognosis of patients with severe COVID-19 disease, whose lungs are so severely diseased that they need to be supported by veno-venous ECMO (extracorporeal membrane oxygenation), is difficult to assess so far. Previously published data from studies, case reports and case series describe a very high mortality in this patient collective. The significance of established clinical prognostic cores in this patient population has not been systematically investigated. This is aggravated by the fact that even at very specialized centers only very few patients from this collective are (can be) treated, so that valid investigations are only possible in a multicenter patient collective. In this registry study, all patients diagnosed with COVID-19 and treated with vv-ECMO in the centers participating in the study should be retrospectively examined. The primary aim of the study is to investigate 30-day survival, secondary objectives include the analysis of different clinical scores at the time of ECMO implantation.

NCT04405973
Conditions
  1. COVID-19
  2. SARS-CoV 2
  3. Extracorporeal Membrane Oxygenation
  4. ARDS
Interventions
  1. Device: vv-ECMO
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: time from ECMO-implantation to death

Measure: overall survival

Time: 30 days

Secondary Outcomes

Description: time from ECMO-implantation to ECMO-explantation

Measure: duration of ECMO treatment

Time: 30 days

Description: time from ECMO-implantation to extubation

Measure: duration of ventilation treatment

Time: 30 days

Description: time from ECMO-implantation to ICU-discharge

Measure: duration of initiation of ECMO treatment to ICU discharge

Time: 30 days
206 Awake Prone Positioning and Oxygen Therapy in Patients With COVID-19 (APRONOX)

The prone position strategy for patients with acute respiratory distress syndrome (ARDS) is simple and cost-effective from the first description on its use in patients with acute respiratory failure to improve hypoxemia. Different studies have investigated its safety and efficacy in various clinical settings, demonstrating that its early use in combination with non-invasive mechanical ventilation (NIV) or high-flow oxygen therapy can reduce intubation rate and mortality in ARDS. In the Coronavirus disease 2019 (COVID-19) pandemic, high-value medicine and resource optimization are critical.

NCT04407468
Conditions
  1. COVID
  2. ARDS
  3. Pneumonia
Interventions
  1. Procedure: Prone position
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Relationship between awake prone position and the tracheal intubation

Measure: To analyze the relationship between the prone position and the need for orotracheal intubation.

Time: 3 months

Secondary Outcomes

Description: See the relationship between the awake prone position and the SaO2/FiO2 INDEX

Measure: The impact of the prone position on the partial oxygen saturation / inspired oxygen fraction index (SaO2 / FiO2).

Time: 3 months

Other Outcomes

Description: Determine the free hours without the need for orotracheal intubation of patients in the prone position.

Measure: Determine the free hours without the need for orotracheal intubation of patients in the prone position.

Time: 3 months
207 Randomised Controlled Trial Comparing High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy Not Requiring Invasive Mechanical Ventilation

Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation. Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are: 1. More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay: 1. Death 2. Acute Myocardial Infarction [AMI] 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] 4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation 5. Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation 2. Similar in terms of major bleeding risk during hospital stay

NCT04408235
Conditions
  1. COVID
  2. Pneumonia, Viral
  3. Coagulation Disorder
Interventions
  1. Drug: Enoxaparin
MeSH:Pneumonia, Viral Pneumonia Hemostatic Disorders Blood Coagulation Disorders
HPO:Abnormality of coagulation Abnormality of the coagulation cascade Pneumonia

Primary Outcomes

Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation

Measure: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:

Time: through study completion, up to 30 days

Secondary Outcomes

Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation Improvement of laboratory parameters of disease severity, including: D-dimer level Plasma fibrinogen levels Mean Platelet Volume Lymphocyte/Neutrophil ratio IL-6 plasma levels

Measure: Any of the following events occurring within the hospital stay

Time: through study completion, up to 30 days

Description: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.

Measure: Mortality at 30 days

Time: 30 days
208 Retrospective Change in the Ratio of Mean Platelet Volume (MPV) to Platellet(PLT) in Covid-19 Pneumonia Patients

Morbidity, mortality and progress depends on systemic inflammation especially in ARDS patients. Previous studies claims that the proportion of mean platellet volume to platellet which can simply be determined with simple blood tests that are performed at admission, might predict the mortality in ARDS patients. Covid-19 pneumonia has a very similar clinical outlook with ARDS. Therefore we decided to research whether that proportion is legitimate for detecting the progress of Covid-19 pneumonia or not.

NCT04408378
Conditions
  1. Coronavirus Infection
Interventions
  1. Other: observation of covid 19 pneumonia
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: İt has been studied that MPV/PLT ratio can show the cl inical couses of several diseases as well as ARDS. we thought that we can identify the coronavirus pneumonia patients earlier, at admission of hospital by using the hemogrames.

Measure: estimation of inflammatory changes in Covid 19 pneumonia by using MVP/PLT ratio

Time: March-May 2020
209 A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

NCT04409262
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Remdesivir
  2. Drug: Tocilizumab
  3. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Time from Randomization to Hospital Discharge (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or Time: Up to Day 28

Secondary Outcomes

Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 60

Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

Time: Up to Day 60

Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, 21, and 28

Time: Days 7, 14, 21, and 28

Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline

Time: Up to Day 60

Measure: Ventilator-Free Days from Randomization to Day 28

Time: Up to Day 28

Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline

Time: Up to Day 60

Measure: Duration of ICU Stay in Days

Time: Up to Day 60

Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.

Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

Time: Up to Day 60

Measure: Mortality up to Day 28 and Day 60

Time: Days 28 and 60

Measure: Mortality Rate on Days 7, 14, 21, 28, and 60

Time: Days 7, 14, 21, 28, and 60

Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed

Time: Up to Day 28

Measure: Duration of Supplemental Oxygen Use

Time: Up to Day 60

Other Outcomes

Measure: Percentage of Participants with Adverse Events (AEs)

Time: Up to 60 days

Measure: Proportion of Participants with any Post-Treatment Infection

Time: Up to 60 days

Measure: Plasma Concentration of Remdesivir

Time: Days 4 and 7
210 A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID 19 Pneumonia and Acute Lung Injury

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT, for the treatment of patients with COVID-19 pneumonia who have mild to moderate ARDS. LIGHT is a cytokine in the TNF super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

NCT04412057
Conditions
  1. COVID-19 Pneumonia
  2. Acute Lung Injury
  3. ARDS
Interventions
  1. Drug: CERC-002
  2. Drug: Placebo
MeSH:Pneumonia Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
HPO:Pneumonia

Primary Outcomes

Description: Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation

Measure: Proportion of patient alive and free of respiratory failure

Time: Baseline to Day 28

Secondary Outcomes

Description: 1-month mortality

Measure: Proportion of subjects who are alive

Time: Baseline to Day 28
211 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY

The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.

NCT04412252
Conditions
  1. COVID-19
Interventions
  1. Drug: Tofacitinib
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Clinical status using ordinal scale

Time: Day 28

Secondary Outcomes

Description: Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Clinical status using ordinal scale

Time: Day 14

Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

Time: Day 14 and Day 28

Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Status of discharged or not requiring supplemental oxygen

Time: Day 28

Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

Measure: Mortality

Time: Day 60
212 A Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)

A Phase 2 study to evaluate the safety and preliminary efficacy of ATYR1923, compared to placebo, in hospitalized patients with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation

NCT04412668
Conditions
  1. SARS-CoV-2 (COVID-19) Severe Pneumonia
Interventions
  1. Drug: ATYR1923 1 mg/kg
  2. Drug: ATYR1923 3 mg/kg
  3. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Incidence of treatment-emergent adverse events (TEAEs)

Time: Baseline through Day 60

Secondary Outcomes

Measure: Time to hospital discharge

Time: Baseline through Day 60

Measure: Time to recovery (World Health Organization [WHO] Ordinal Scale score ≤3)

Time: Baseline through Day 60

Measure: Proportion of patients achieving recovery by Day 14 and Day 28

Time: Baseline through Day 14 and Day 28

Measure: Duration of supplemental oxygen (O2) requirement

Time: Baseline through Day 60

Measure: Number of days with fever (temperature >100.4ºF [38.0ºC])

Time: Baseline through Day 14 or discharge

Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60

Time: Baseline through Day 60

Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score

Time: Baseline through Day 60

Measure: All-cause mortality at Days 14, 28, and 60

Time: Baseline through Day 60
213 Phase II Study of Low Dose Pulmonary Irradiation in Patients With COVID-19 Infection of Bad Prognosis

The administration of low-dose lung irradiation produces anti-inflammatory effects that will decrease the pulmonary inflammatory response. The present study will evaluate the efficacy of treatment with low-dose pulmonary radiotherapy added to standard support therapy, in hospitalized patients with respiratory symptoms due to COVID-19 pneumonia, who do not experience improvement with conventional medical therapy and are not subsidiaries of ICU

NCT04414293
Conditions
  1. COVID
  2. Pneumonia, Viral
Interventions
  1. Radiation: Lung Low Dose Radiation
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical improvement of respiratory symptoms due to COVID-19 pneumonia after the treatment, measured as blood oxygen saturation levels

Measure: blood oxygen saturation level

Time: 48 hours

Description: radiological improvement of respiratory symptoms due to COVID-19 pneumonia after the treatment.

Measure: Torax X-ray

Time: 48 hours

Secondary Outcomes

Description: number of days of hospital stay.

Measure: Hospitalization

Time: 2 months

Description: Number of days free of assisted mechanical respiration.

Measure: days free of assisted mechanical respiration

Time: 3 month

Description: number of deaths

Measure: Mortality

Time: 3 months
214 Echocardiography in Critically-ill Patients With COVID-19 Pneumonia

Critical care echocardiography (CCE) has been widely used since the 10 last years. Covid outbreak leads that many patients with acute respiratory failure were admitted in the ICU. Many of these patients were ventilated and developed ARDS. Some of them developed deep vein thrombosis and pulmonary embolism. Nothing is already described about the cardiac function and the hemodynamics in these patients (how many RV failure, LV systolic dysfunction,...). The echo group of the cardiodynamix section of European society of intensive care medicien (ESICM) aims to promote CCE and evaluate its interest. The objective is to retrospectively enter in an international database all the echo studies done as usual care in these patients to evaluate (i) incidence of RV failure, (ii) incidence of LV systolic function, (iii) incidence of other patterns. Another objective will be to look for any association between some patterns and respiratory strategy, blood gas analysis, systemic hemodynamics. The echo studies were done and will be reported following one of the recent systematic review published by the same group (Huang S et al. AOIC 2020).

NCT04414410
Conditions
  1. COVID
  2. Sars-CoV2
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: LV systolic dysfunction is defined as an ejection fraction < 45%

Measure: Incidence of Left ventricular systolic dysfunction

Time: Up to 28 days

Description: RV failure is defined as RV/LV end-diastolic area > 0.8

Measure: Incidence of RV failure

Time: up to 28 days

Description: Vasoplegia is defined as a normal or supranormal LV ejection fraction without echocarduiographic signs of hypovolemia.

Measure: Incidence of Vasoplegia

Time: Up to 28 days

Description: Hypovolemia is defined as inspiratory collaspe of the superior vena cava in ventilated patients or virtual inferior vena cava in spontaneously breathing patients.

Measure: Incidence of Hypovolemia

Time: Up to 28 days

Secondary Outcomes

Description: Plateau pressure and RV size

Measure: Relation between plateau pressure and RV failure

Time: Up to 28 days

Description: Tidal volume and RV size

Measure: Relation between tidal volume and RV failure

Time: Up to 28 days

Description: PaO2, PaO2/FiO2, and RV size

Measure: Relation between PaO2 and RV failure

Time: Up to 28 days

Description: PaCO2 and RV size

Measure: Relation between PaCO2 and RV failure

Time: Up to 28 days

Description: PEEP and RV size

Measure: Relation between PEEP and RV failure

Time: Up to 28 days
215 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia

This proof of concept study will take place in the US and other countries in approximately 15 clinical sites and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. 20 patients will receive opaganib in addition to standard of care twice each day for 14 days. 20 will receive matching placebo in addition to standard of care unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

NCT04414618
Conditions
  1. Coronavirus Infections
Interventions
  1. Drug: Opaganib
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To compare the total oxygen requirement (area under the curve) for each arm using daily supplemental oxygen flow (L/min) over 14 days

Measure: Measurement of the oxygen requirement

Time: 14 days

Secondary Outcomes

Description: To comparing the time required between arms to achieve 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min

Measure: Measurement of the reduction in oxygen requirement.

Time: 14 days

Description: To comparing the proportion of patients in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14

Measure: Eliminating supplemental oxygen

Time: 14 days

Description: To compare the proportion of afebrile patients in each arm at Day 14 via measurement of temperature.

Measure: Elimination of fever

Time: 14 days

Description: To compare the time in each arm to negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab for SARS-CoV-2

Measure: Time to negative swabs for SARS-CoV-2 by PCR post treatment

Time: 6 weeks

Description: To comparing the time in each arm to achieve negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab for SARS-CoV-2 during treatment

Measure: Time to negative swabs for SARS-CoV-2 by PCR at Day 14

Time: 14 days

Description: To compare the percentage of patients in each arm who require intubation and mechanical ventilation by Day 14

Measure: Intubation and mechanical ventilation requirements

Time: From screening phase and every day from day 1 to day 14 of treatment

Description: To compare the time in each arm for the patient to require mechanical ventilation.

Measure: Evaluation of the time to mechanical ventilation

Time: From screening phase and every day from day 1 to day 14 of treatment

Description: To compare the proportion of patients in each arm, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14

Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14

Time: From screening phase and every day from day 1 to day 14 of treatment

Description: To compare the mortality in each arm 30 days post-baseline.

Measure: Evaluation of mortality 30 days post-baseline

Time: 30 days after day 1 of treatment

Other Outcomes

Description: To compare the number of all treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Measure: Safety

Time: 6 weeks
216 the Determination of Extracellular Water (ECW) Which is Detected by Bioimpedence Method on Severe and Mild Covid 19 Pneumonia Clinical Course

According to various studies Covid 19 pneumonia has a very similar clinical course to Acute Respiratory Distress Syndrome (ARDS) which has clarified by Berlin definition. Based on this similarity, extracellular fluid of lungs and diffuse alveolar damage should be observed in covid 19 pneumonia as well. Extracellular water (ECW) can be determine by using whole body bioimpedence system (NİCaS). The aim of this study is to investigate the effect of ECW on the clinical apperence of covid 19 pneumonia clinical course.

NCT04416009
Conditions
  1. Extracellular Fluid Alteration
  2. Corona Virus Infection
Interventions
  1. Device: NİCaS
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Changes of three measurements of extracellular water in both lungs

Measure: ECW

Time: three measurements with half an hour intervals
217 PREEMPTIVE THERAPY WITH COLCHICINE IN PATIENTS OLDER THAN 60 YEARS WITH HIGH RISK OF SEVERE PNEUMONIAE DUE TO CORONAVIRUS SARS-CoV2 (COVID-19)

This is a phase 3 clinical trial, randomized, single-center, opened, controlled, to evaluate efficacy and safety of early administration of colchicines in patients older than 60 years, with high risk of pulmonary complications due to coronavirus SARS-CoV2 (COVID-19). An approximately number of 954 subjects meeting all inclusion and none exclusion criteria will be randomized either to receive colchicines or symptomatic treatment with paracetamol during 21 days.

NCT04416334
Conditions
  1. SARS-CoV-2 Infection (COVID-19)
Interventions
  1. Drug: Colchicine plus symptomatic treatment (paracetamol)
  2. Drug: Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations)
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Number of participants who die due to COVID-19 infection

Time: 21 days post-randomization

Measure: Number of participants who require hospitalization due to COVID-19 infection

Time: 21 days post-randomization

Other Outcomes

Description: not delayed more than 48 hours from initial symptoms

Measure: A confirmed diagnosis from COVID-19 infection (by positive PCR test) will be mandatory .

Time: 48 hours
218 Treatment Effect of Nafamostat Mesylate in Patients With COVID-19 Pneumonia: Open Labelled Randomized Controlled Clinical Trial

In-vitro studies revealed that nafamostat mesylate has antiviral activity against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-inflammatory and anti-coagulation effect. However, there is no clinical studies on the efficacy of nafamostat in patients with COVID-19. This study is conducted to evaluate the clinical efficacy of nafamostate mesylate in adult patients hospitalized with COVID-19 pneumonia.

NCT04418128
Conditions
  1. Corona Virus Infection
  2. COVID-19
Interventions
  1. Drug: Nafamostat Mesylate
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status. * Seven-category ordinal scale of clinical status not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death.

Measure: Proportion of patients with clinical improvement

Time: Day 14 & Day 28

Secondary Outcomes

Description: Time to clinical improvement (TTCI) was defined as time from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first.

Measure: Time to clinical improvement (TTCI)

Time: up to 28 days

Description: * Seven-category ordinal scale of clinical status not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death. Higher scores of Seven-category ordinal scale mean serious clinical status.

Measure: Clinical status assessed by 7-category ordinal scale

Time: days 7, 14, and 28

Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The range of NEW score is from zero to 23. Higher scores of NEWS mean the higher risk of poor outcomes. The NEW Score is being used as an efficacy measure.

Measure: Change in National Early Warning Score (NEWS)

Time: Day 1 trough Day 28

Measure: Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours

Time: Day 1 through Day 28

Measure: Duration of hospitalization

Time: Day 1 through Day 28

Measure: Duration of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 28

Measure: Incidence of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 28

Measure: Duration of new supplement oxygen use

Time: Day 1 through Day 28

Measure: Incidence of new supplement oxygen use

Time: Day 1 through Day 28

Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 28

Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 28

Measure: Mortality at day 28

Time: Day 1 through Day 28

Measure: Time (days) from treatment initiation to death

Time: Day 1 through Day 28

Measure: Proportions of patients with a negative nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR

Time: days 3, 7, 10, 14, and 21

Measure: Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR

Time: days 3, 7, 10, 14, and 21

Measure: Adverse events that occurred during treatment

Time: Day 1 through Day 28
219 A Pilot Study to Explore the Efficacy and Safety of Rescue Therapy With Antibodies From Convalescent Patients Obtained With Double-filtration Plasmapheresis (DFPP) and Infused in Patients With Coronavirus Disease 2019 (COVID-19) and Need of Oxygen Support Without Mechanical Ventilation

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Moreover, plasma-exchange is expensive and requires large volumes of substitution fluid With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The use of plasma as a substitution fluid further increases treatment costs and is associated with risk of infections, allergic reactions and citrate-induced hypocalcemia. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. The aforementioned limitations of plasma therapy can be in part overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP)3. During DFPP, plasma is separated from cellular components by a plasma filter, and is then allowed to pass through a fractionator filter. Depending on the membrane cut-off, the fractionator filter retains larger molecules and returns fluid along with smaller molecules to the circulation. Thus, the selection of a membrane with an appropriate sieving coefficient for IgG allows to efficiently clear autoantibodies in patients with antibody-mediated diseases (e.g., macroglobulinemia, myasthenia gravis and rheumatoid arthritis) with negligible fluid losses and limited removal of albumin and coagulation factors1. In patients with severe membranous nephropathy and high titer of autoreactive, nephritogenic antibodies against the podocyte-expressed M type phospholipase A2 receptor (PLA2R), DFPP accelerated anti PLA2R depletion4. Measurement of the antibody titer in treated patient and recovered fluid showed that antibody removal was extremely effective and that large part of antibodies was removed during the first DFPP procedure. This therapeutic regimen was safe and well tolerated and easy to apply4. In an ongoing pilot study we found that the same methodological approach can be used to remove circulating antibodies from patients who recovered from COVID 19 and to infuse these antibodies in patients with active viral infection. Treatment was well tolerated and preliminary findings are encouraging. Thus, in this novel pilot study we aim to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for patients with earlier stages of coronavirus (COVID-19) pneumonia requiring oxygen supply without mechanical ventilation.

NCT04418531
Conditions
  1. Pneumonia, Viral
  2. Corona Virus Infection
Interventions
  1. Biological: Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Time to weaning of oxygen support

Time: Through study completion, an average of 3 months

Secondary Outcomes

Measure: Chest XR or CT scan evaluation

Time: Changes during the study up completion, an average of 3 months

Measure: Survival,

Time: Through study completion, an average of 3 months

Measure: Viral titer

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Measure: Anti COVID 19 IgG antibodies

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Measure: Anti COVID 19 IgM antibodies

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: C5a concentration

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: C3a concentration

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum C5b-9 concentration Marker of complement activation

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum IL-6 levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum IL-1b levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum IFNγ levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum MCP-1 levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum TNFα levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum IL-10 levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum IL-2 levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

Description: Marker of complement activation in plasma.

Measure: Serum IL-7 levels

Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
220 Multicentric Pragmatic Randomized Controled Trial to Evaluate the Efficacy Chloroquine or Hydroxychloroquine for Five Days in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19

Facing the challenge of finding an efficient treatment for COVID-19, the viral pneumonia caused by the Coronavirus SARS-Cov-2, this study intended to test if Chloroquine or Hydroxychloroquine, two drugs with strong in-vitro antiviral role proven by numerous studies and with a well defined safety profile established, for efficacy in treating COVID-19 and improving an ordinal primary outcome composed by a 9-levels scale, which was recomended by the World Health Organization.

NCT04420247
Conditions
  1. COVID
  2. COVID-19
  3. SARS-CoV 2
  4. Coronavirus
  5. Corona Virus Infection
Interventions
  1. Drug: Chloroquine
  2. Drug: Hydroxychloroquine
  3. Other: standard care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of the clinical status of patients on the 14th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.

Measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)

Time: 14 days after randomization

Secondary Outcomes

Description: Evaluation of the clinical status of patients on the 5th, 7th, 10th and 28th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.

Measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)

Time: 5, 7, 10 and 28 days after randomization

Description: All-cause mortality at 28 days after randomization

Measure: Mortality

Time: 28 days after randomization

Description: Number of days without need of Mechanical Ventilation at 28 days after randomization

Measure: Ventilation free days

Time: 28 days after randomization

Description: ICU Lenght of Stay on survivors at 28 days after randomization

Measure: ICU Lenght of Stay

Time: 28 days after randomization

Description: Hospital Lenght of Stay on survivors at 28 days after randomization

Measure: Hospital Lenght of Stay

Time: 28 days after randomization

Description: Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.

Measure: Acute Kidney Disease incidence

Time: 28 days after randomization

Description: Percentage of patients needing dialysis sometime until the 28th day.

Measure: Percentage of patients needing dialysis

Time: 28 days after randomization

Description: Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).

Measure: Coagulopathy incidence

Time: 28 days after randomization

Description: Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization

Measure: Mean of C Reactive Protein Levels

Time: 5, 7, 10, 14 and 28 days after randomization

Description: Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.

Measure: Sequential Organ Failure Assessment (SOFA) scores

Time: 5, 7, 10, 14 and 28 days after randomization

Description: Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.

Measure: Neutrophils/lymphocytes ratio

Time: 5, 7, 10, 14 and 28 days after randomization

Other Outcomes

Description: Safety outcome: Any kind of arrhythmia identified by the attending physician at the time of the intercurrence, confirmed by an electrocardiogram (ECG), sometime until the 28th day

Measure: Arrhythmia

Time: 28 days after randomization
221 Low Dose Radiotherapy as Antinflammatory Treatment for COVID-19 Pneumonitis

SARS-CoV-2 is causing an unprecedented stress on healthcare systems around the world, due to its high rate of infection and the high morbidity and mortality. The COVID-19 infection triggers an inflammatory cascade with cytokine synthesis, prompting the immune response. Low dose radiotherapy (LD-RT) (≤ 100 cGy) induces an anti-inflammatory response, lowering levels of pro-inflammatory cytokines such as IL-1β or inhibit leukocyte recruitment. LD-RT has been used historically for the pneumonia treatment reporting a rapid clinical improvement (within the first week), as well as a reduced mortality (from around 30% to 10%). Considering these results, LD-RT can potentially afford a therapeutic benefit against SARS-CoV-2. The study purpose is to evaluate prospectively the safety and efficacy of LD-RT for SARS-CoV-2.

NCT04420390
Conditions
  1. Covid19
Interventions
  1. Radiation: Radiotherapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Radiological results: Radiological worsening, improvement or without significant changes

Measure: Radiological response

Time: 3 days after low dose radiation

Description: Radiological results: Radiological worsening, improvement or without significant changes

Measure: Radiological response

Time: 7 days after low dose radiation

Secondary Outcomes

Description: Remission of respiratory symptoms

Measure: Remission of respiratory symptoms

Time: up to 6 months

Description: Time to SPO2>94% or PaO2/FiO2 >350mmHg without oxygen

Measure: SPO2 and PaO2/FiO2

Time: 7 days

Description: Occurrence and grade of CTCAE 5.0 adverse events

Measure: Adverse events

Time: 1 year

Description: Duration of hospitalization

Measure: Hospitalization

Time: 3 months

Description: Overall survival

Measure: Overall survival

Time: 1 month

Description: ferritin value (ng/mL)

Measure: Ferritin value

Time: 1 day after low dose radiation

Description: ferritin value (ng/mL)

Measure: Ferritin value

Time: 2 days after low dose radiation

Description: ferritin value (ng/mL)

Measure: Ferritin value

Time: 3 days after low dose radiation

Description: blood cell count (unit/L)

Measure: blood cell count

Time: 1 day after low dose radiation

Description: blood cell count (unit/L)

Measure: blood cell count

Time: 2 days after low dose radiation

Description: blood cell count (unit/L)

Measure: blood cell count

Time: 3 days after low dose radiation

Description: C-reactive protein (mg/dl)

Measure: C-reactive protein

Time: 1 day after low dose radiation

Description: C-reactive protein (mg/dl)

Measure: C-reactive protein

Time: 2 days after low dose radiation

Description: C-reactive protein (mg/dl)

Measure: C-reactive protein

Time: 3 days after low dose radiation

Description: D-dimer (ng/ml)

Measure: D-dimer

Time: 1 day after low dose radiation

Description: D-dimer (ng/ml)

Measure: D-dimer

Time: 2 days after low dose radiation

Description: D-dimer (ng/ml)

Measure: D-dimer

Time: 3 days after low dose radiation

Description: LDH levels (UI/L)

Measure: LDH levels

Time: 1 day after low dose radiation

Description: LDH levels (UI/L)

Measure: LDH levels

Time: 2 days after low dose radiation

Description: LDH levels (UI/L)

Measure: LDH levels

Time: 3 days after low dose radiation
222 Characterization of Persistent Pulmonary Abnormalities Following COVID-19 Pneumonia

Severe Acute Respiratory Syndrome SARS-CoV-2, name of the Coronavirus Group of international Committee on taxonomy of viruses, is an emerging virus from the family of coronaviridae, responsible for the COVID-19 pandemic. This infection can progress to viral pneumonia, and in 3% of cases up to acute respiratory distress syndrome (ARDS) which conditions the prognosis of the disease. Due to its unusual clinical presentation with a risk of sudden deterioration on the 8th day as a result of possible hyperinflammatory response, the respiratory impairment of COVID is unique and many questions remain unanswered concerning its evolution once the acute phase has passed. Knowledge of the evolution of pulmonary involvement, particularly in patients requiring hospitalization, can help reduce the morbidity linked to the persistent abnormalities identified by establishing early therapeutic management. It can also provide a better understanding of the mechanisms of pulmonary involvement in the acute phase. Current data regarding the acute phase of COVID-19 suggest that persistent abnormalities remain distant from this infection at all levels of the respiratory system: gas exchange, perfusion, ventilatory mechanics, and interstitial lung disease. The main objective is to characterize persistent gas exchange anomalies 4 months after documented COVID-19 pneumonia, resulting in oxygen desaturation and requiring hospitalization.

NCT04422613
Conditions
  1. Pneumonia, Viral
Interventions
  1. Diagnostic Test: pulmonary anomalies 4 months after documented COVID-19 pneumonia
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Alteration of the DLCO test defined by a corrected DLCO value <70% of theoretical and / or desaturation in the 6 Minute Walk Test (loss of 4% or more of SpO2)

Measure: Alteration of the DLCO

Time: 4 month

Secondary Outcomes

Description: The mechanism of the alteration of gas exchanges will be specified by the analysis of the values obtained during the diffusing CO / NO test, at 4 month after COVID- 19 pneumonia

Measure: Mechanism of the alteration of gas exchanges

Time: 4 month

Description: The mechanism of the alteration of gas exchanges will be specified by the analysis of the other values obtained during the measurement of lung volumes in respiratory function tests at 4 month after COVID- 19 pneumonia

Measure: Measurement on lung volumes

Time: 4 month

Description: The mechanism of the alteration of gas exchanges will be specified by the analysis of the other values obtained during chest CT-scan at 4 month after COVID- 19 pneumonia

Measure: mechanism of the alteration of gas exchanges by chest scan

Time: 4 month

Description: The mechanism of the alteration of gas exchanges identified will be specified by the analysis of the other values obtained during pulmonary scintigraphy, at 4 month after COVID- 19 pneumonia :

Measure: mechanism of the alteration of gas exchanges by scintigraphy

Time: 4 month

Description: the existence of respiratory symptoms, defined by dyspnea, cough, sputum, haemoptysis, chest pain, sign of right ventricular failure, sleep disorders or a 6-minute walk test value <80% of theoretical, at 4 month after COVID- 19 pneumonia

Measure: Respiratory symptom

Time: 4 month

Description: the existence of persistent bronchial or ventilatory anomalies at 4 months, defined on current respiratory function tests (plethysmography, forced oscillometry test, diaphragmatic explorations, measurement of exhaled NO)

Measure: Bronchial or ventilatory anomalies

Time: 4 month

Description: Persistent respiratory anomalies at 4 months will be evaluated at 12 months of the acute episode by an appropriate paraclinical assessment : mechanism of the alteration of gas exchanges, Respiratory symptom and bronchial or ventilatory anomalies will be evaluated

Measure: Persistent respiratory anomalies

Time: 12 month
223 Imatinib for the Treatment of SARS-COV-2 Induced Pneumonia: A Pilot Study

A randomized controlled pilot study on the safety & efficacy of imatinib for the treatment of patient with moderate to severe SARS-COV-2 induced pneumonia.

NCT04422678
Conditions
  1. COVID-19
Interventions
  1. Drug: Imatinib Mesylate
  2. Drug: Standard of Care
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Proportion of patients with COVID-19 pneumonia progressed to critical illness in need for invasive mechanical ventilation.

Measure: Primary endpoint: Disease Progression

Time: 30 Days

Secondary Outcomes

Description: Improvement of Hypoxic index( PaO2 / FiO2) calculated daily

Measure: Improvement in Hypoxic Index

Time: From inclusion to 30 days follow up

Description: Hospital Length of stay

Measure: Hospital Length of Stay

Time: From inclusion to 30 days follow up

Description: Days on mechanical ventilation for patients needing intubation & invasive mechanical ventilation

Measure: Days on invasive mechanical ventilation

Time: From inclusion to 30 days follow up

Description: Difference in the median levels of serum IL-6, serum ferritin, CRP at the end of the follow up period between all groups

Measure: Inflammatory Markers

Time: From inclusion to 30 days

Description: Rate of viral clearance as monitored by SARS-COV-2 PCR

Measure: Viral clearance

Time: From inclusion to 30 days

Description: Difference in the overall evaluation of pulmonary infiltrative (improving / deteriorating) as assessed by imaging (Chest X-ray or Non-contrast pulmonary CT)

Measure: Radiological assessment

Time: From inclusion to 30 days

Description: Rate of serious adverse events (SAEs)

Measure: Safety of Imatinib

Time: From inclusion to 60 days
224 Bruk av Ultralyd i Evaluering av Pasienter Med Mistenkt COVID-19 Infeksjon i Norge

In light of the ongoing COVID-19 epidemic in Norway, it is paramount to develop and utilize clinical tools for assessing and risk stratifying patients with suspected coronary infection in the emergency departments. Diagnostic use of ultrasound in viral pneumonias, including COVID-19 has proved to be very useful. The use of ultrasound will assist in quick detection of lung pathology compatible with increasing severity of the COVID-19 disease. At the same time, the use of ultrasound diagnostics in the emergency department could improve logistics and reduce potential exposure of the corona virus to other health personnel. The purpose of the study is to assess whether ultrasound findings correlates with physical examination, labs, and other imaging diagnostics in patients with suspected or diagnosed COVID-19 disease, as well as assessing whether ultrasound diagnostics can assist in risk stratification. The project is conducted as a prospective multicenter study where ultrasound diagnostics will be performed on patients with suspected coronary infection in the emergency departments. Data collection takes place as part of the daily clinical evaluation of acute patients in the emergency departments. The project is planned to be completed towards the end of 2025.

NCT04422691
Conditions
  1. COVID-19
  2. Pneumonia, Viral
  3. Pulmonary Infection
Interventions
  1. Diagnostic Test: Lung ultrasound
MeSH:Infection Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: 30-day mortality

Measure: Mortality

Time: up to 30 days

Description: In-hospital treatment level, e.g. discharge from ED, observational unit, ward, ICU.

Measure: Level-of-care

Time: up to 7 days

Secondary Outcomes

Description: in days

Measure: In-hospital length of stay

Time: Up to 30 days

Measure: Oxygen usage in the emergency department

Time: Within 24 hours

Description: in hours

Measure: Emergency department length of stay

Time: Within 24 hours

Measure: Antibiotics usage

Time: Within 24 hours

Other Outcomes

Description: Clinical correlation between ultrasound findings and vital signs, labs, blood gas and other diagnostic modalities.

Measure: Clinical correlation

Time: Within 3 days
225 Thrombosis Risk Assessment May Predict Clinical Presentation and Length of Hospital Stay in Covid-19 Pneumonia

Covid-19 mainly affects the respiratory system. Multiple organ dysfunction and a particularly progressive respiratory insufficiency along with a widespread coagulopathy presumed to be due to infection-associated inflammation and the resulting cytokine storm, are strongly associated with high mortality rates. In this study, the association between thrombosis risk and clinical presentation of Covid-19 is investigated.

NCT04423315
Conditions
  1. Corona Virus Infection
  2. Thromboembolic Disease
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Thrombosis Thromboembolism
HPO:Pneumonia Thromboembolism

Primary Outcomes

Description: from admission to discharge expressed in days

Measure: length of hospital stay

Time: 2 months
226 Possibilities of Chest Magnetic Resonance Imaging (MRI) in Diagnostics of COVID-19. The Use of MRI to Assess Lung Damage in Patients With Coronavirus Infection

Since the onset of the COVID-19 pandemic, the importance of chest computed tomography (CT) in detecting signs of viral pneumonia has become clear from the literature. However, the increased patient flow creates an additional pressure on CT centers. We believe, the use of chest magnetic resonance imaging (MRI) can help to test patients for CОVID-19 when CT scan is not available. Lung MRI may be useful in routing a patient in a difficult epidemiological situation.

NCT04424355
Conditions
  1. Coronavirus Infections
  2. Pneumonia
Interventions
  1. Diagnostic Test: Chest MRI
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Expected number - more than two zones

Measure: Number of zones of pulmonary parenchyma corresponding to viral pneumonia detected by chest MRI in comparison with CT scan

Time: Upon completion, up to 1 year
227 Prone Positioning on Admission for Hospitalized COVID-19 Pneumonia Protocol

A pilot study to investigate the effects of the prone positioning (PP) on hospital patients diagnosed with COVID-19 pneumonia. Investigators that early self-proning may prevent intubation and improve mortality in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2). Up to 100 participants with a primary diagnosis of confirmed COVID-19 pneumonia will be enrolled to the study. All participants will be screened and those that meet inclusion and exclusion criteria will be enrolled to one of two groups: one with prone positioning (on the belly) and the other with standard supine positioning (on the back). The patient and nursing staff will monitor times spent in various positions. Outcome measures include incidence of intubation, max oxygen requirements, length of hospital stay, ventilator-free days, worsening of oxygenation saturation, and mortality.

NCT04424797
Conditions
  1. COVID-19
Interventions
  1. Other: Prone Positioning
  2. Other: Supine Positioning
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Incidence of intubation

Measure: Incidence of intubation

Time: Through study completion, an average of 6 days

Secondary Outcomes

Description: Measure of maximum oxygen requirements

Measure: Maximum oxygen requirement

Time: Through study completion, an average of 6 days

Description: Measured in days of hospitalization

Measure: Length of Stay

Time: Through study completion, an average of 6 days

Description: Measured in days not on a ventilator

Measure: Ventilator-free days

Time: Through study completion, an average of 6 days

Description: Whether or not the participant met treatment failure descriptions

Measure: Treatment failure of prone positioning due to worsening SpO2 status while prone

Time: Through study completion, an average of 6 days

Description: Whether or not the participant died while hospitalized

Measure: Mortality

Time: Through study completion, an average of 6 days
228 the Effect of HFNC Treatment on Mortality and Length of ICU Stay in Patient With COVID-19 Pneumonia

coronavirus disease 2019 related pneumonia is causing acute respiratory failure and this is the most common reason for ICU admission. We have several different way for respiratory support. HFNC is one of the new technics for oxygen support. Our main purpose to observe the effect of HFNC on coronavirus disease 2019 patients' ICU stay and mortality.

NCT04424836
Conditions
  1. Coronavirus Infection
  2. Pneumonia, Viral
  3. Acute Respiratory Failure
Interventions
  1. Device: high flow nasal cannula device
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: the mortality rate of patients

Measure: short term mortality

Time: in 28 days.

Description: means the stay day of patients in intensive care unit

Measure: icu stay

Time: up to 28 days

Secondary Outcomes

Description: partial oxygen pressure, partial carbon dioxide pressure . both measured in mmhg

Measure: blood gases

Time: at the admission time and 24th hour
229 A Randomized, Open-label Study of the Vascular and Microbiologic Efficacy of Dipyridamole Plus Standard Care vs. Standard Care in Hospitalized COVID19 Patients

Brief Summary: The goal here is to evaluate dipyridamole in treating respiratory tract infection and circulatory dysfunction due to SARS-CoV-2 coronavirus in hospitalized CVID-19 patients. Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). The infection is associated with a deleterious inflammatory response and a prothrombotic state in addition to tissue damage from direct viral entry and proliferation. Dipyridamole has anti-platelet and anti-inflammatory effects. The drug was recently demonstrated to have anti-SARS-Cov-2 effect primarily in vitro. The concentration causing anti-viral effect in vitro is within that in the blood of humans taking this drug. As an oral tablet, it has the advantage of easy administration. Anti thrombotic, anti viral and anti inflammatory actions of this drug may be efficacious and safe in hospitalized subjects

NCT04424901
Conditions
  1. COVID-19 Pneumonia
  2. Vascular Complications
Interventions
  1. Drug: Dipyridamole
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: D-dimer and platelet count

Measure: Coagulation system

Time: 9 days

Secondary Outcomes

Description: Evaluate for a non-detection from nasopharyngeal swab and in stool

Measure: Viral Detection

Time: 9 days

Other Outcomes

Description: Survival Status Alive

Measure: Survival

Time: 9 days

Description: Change in the markers CRP/Ferritin

Measure: Inflammatory Markers

Time: 9 days

Description: Change in Lymphocyte Count/ Fibrinogen/Cardiac Troponin

Measure: Blood Markers

Time: 9 days

Description: Change in PT, PTT

Measure: Coagulation Markers

Time: 9 days

Description: Change in SpO2/ imaging

Measure: Pulmonary Status

Time: 9 days

Description: Change in fever, cough, sputum

Measure: Clinical Status

Time: 9 days
230 Efficacy and Safety of Darunavir/Cobicistat vs. Lopinavir/Ritonavir in the Management of Patients With COVID-19 Pneumonia in Qatar

Coronavirus Disease 2019 (COVID-19) is a disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. It was first isolated in Wuhan, China in December 2019 and then rapidly spread to the rest of the world posing a severe threat to global health. Many therapeutics have been investigated for the treatment of this disease with inconclusive outcomes. Protease inhibitors are one of the proposed agents, but their use is limited to their significant drug interactions and side effects. The aim of this study is to compare the efficacy and safety outcomes of Darunavir/Cobicistat versus Lopinavir /Ritonavir in the treatment of patients with COVID-19 pneumonia in Qatar.

NCT04425382
Conditions
  1. Coronavirus
  2. COVID
  3. Pneumonia
Interventions
  1. Drug: Darunavir/Cobicistat
  2. Drug: Lopinavir/Ritonavir
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical Improvement is defined as the time to normalization of fever (defined as temperature <37.8 oC for 72 hours) and/or resolution of baseline sign/symptoms, without the need for symptomatic treatment Virological clearance is defined as the time to two consecutive negative COVID-19 PCR samples

Measure: Time to Clinical Improvement and/or Virological Clearance (Composite Endpoint)

Time: Up to 90 days

Secondary Outcomes

Description: o Defined as two consecutive negative COVID-19 PCR samples

Measure: Percentage of Virological Clearance

Time: At day 14, day 21, and day 28.

Description: o Defined as the need for respiratory support, vasopressor use, or corticosteroids/immunomodulation therapy

Measure: Percentage of Clinical Deterioration

Time: Up to 28 days

Measure: Incidence of Adverse Events

Time: Up to 28 days

Measure: Length of Hospital Stay

Time: Up to 90 days

Measure: All-cause Mortality

Time: At 30 days
231 A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia

The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of MK-5475 after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that MK-5475 when administered to participants with COVID-19 pneumonia and hypoxemia improves arterial oxygenation as measured by the ratio of blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio) compared to placebo.

NCT04425733
Conditions
  1. Coronavirus Disease 2019 (COVID-19)
  2. Pneumonia
  3. Hypoxemia
Interventions
  1. Drug: MK-5475
  2. Drug: Placebo
MeSH:Pneumonia Hypoxia
HPO:Hypoxemia Pneumonia

Primary Outcomes

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.

Measure: Number of Participants Who Experience an Adverse Event (AE)

Time: Up to ~Day 21

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.

Measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Time: Up to ~Day 7

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.

Measure: Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.

Measure: Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.

Measure: Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.

Measure: Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.

Measure: Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.

Measure: Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.

Measure: Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

Time: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
232 A Randomized,Double Blinded, Double Dummy, Parallel Controlled Clinical Trial for Azvudine in the Treatment of Novel Coronavirus Pneumonia (COVID-19)

To evaluate the efficacy and safety of azvudine in treatment of COVID-19

NCT04425772
Conditions
  1. COVID-19
Interventions
  1. Drug: FNC+Standard of Care
  2. Drug: FNC dummy tablet+Standard of Care
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: (reduction) in viral load from baseline

Measure: Change (reduction) in viral load from baseline

Time: On day 7 and 14

Secondary Outcomes

Description: proportion of subjects change from mild or moderate type to severe type

Measure: proportion of subjects change from mild or moderate type to severe type

Time: up to 21 days

Description: proportion of subjects change from severe type to critical type

Measure: proportion of subjects change from severe type to critical type

Time: up to 21 days

Description: novel coronavirus nucleic acid conversion rate

Measure: novel coronavirus nucleic acid conversion rate

Time: up to 21 days

Description: Novel coronavirus nucleic acid negative conversion time

Measure: Novel coronavirus nucleic acid negative conversion time

Time: up to 21 days

Description: TIme(Days);Proportion(percent)

Measure: The time and proportion of improvement in pulmonary imaging

Time: up to 21 days

Description: TIme(Days);Proportion(percent)

Measure: Time and proportion of temperature return to normal

Time: up to 21 days

Description: TIme(Days);Proportion(percent)

Measure: time and rate of improvement of respiratory symptoms and signs (lung rhones, cough, sputum, sore throat, etc.)

Time: up to 21 days

Description: TIme(Days);Proportion(percent)

Measure: time and rate of improvement of diarrhea, myalgia, fatigue and other symptoms

Time: up to 21 days

Description: Changes of blood oxygen detection index

Measure: Changes of blood oxygen detection index

Time: up to 21 days

Description: Frequency of requirement for supplemental oxygen or non-invasive ventilation

Measure: Frequency of requirement for supplemental oxygen or non-invasive ventilation

Time: up to 21 days

Description: Frequency of adverse events

Measure: Frequency of adverse events

Time: up to 21 days
233 Evaluation of Ivermectin, Aspirin, Dexamethasone and Enoxaparin as Treatment of covid19

The associated use of Ivermectin, aspirin, dexamethasone, and enoxaparin (in different combinations and doses) will reduce the impact of COVID infection 19, the need of admission to the intensive care unit, and mortality.

NCT04425863
Conditions
  1. Severe Acute Respiratory Syndrome
  2. Ventilation Pneumonitis
Interventions
  1. Drug: Ivermectin 5 MG/ML oral solution, Aspirin 250 mg tablets
  2. Other: Ivermectin 5 mg/mL oral solution, Dexamethasone 4-mg injection, Aspirin 250 mg tablets
  3. Other: Ivermectin 5 MG/ML oral solution, Dexamethasone 4-mg injection, Enoxaparin injection. Inpatient treatment with mechanical ventilation in ICU.
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of patients who did not go to a more severe stage of disease or die (i.e. they neither go from mild to moderate or severe, nor go from moderate to severe or die, if they had been already enrolled in a severe condition)

Measure: Patients Who Improved Their Condition or Did Not Worsen it

Time: 7 days

Description: Number of patients needing ICU-treatment including mechanical ventilation after 2-week treatment

Measure: ICU-treated Patients After 2-week Treatment

Time: 14 days

Description: Patients who died within 30 days after enrollment

Measure: Mortality

Time: 30 days

Description: Patients who needed dose adjustment of any of the drugs involved in the treatment protocol

Measure: Patients Needing Drug Dose Adjustment

Time: 14 days

Description: Patient presenting serious adverse events

Measure: Adverse Events

Time: 14 days
234 Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Chloroquine + Low Dose Losartan Compared to Chloroquine Monotherapy in Subjects With SARS-CoV-2 Pneumonia

Study design Phase 2, double blinded, single-center, 1:1 randomized clinical trial of Chloroquine vs Chloroquine/losartan for the treatment of SARS-CoV-2 pneumonia in non-critically ill subjects

NCT04428268
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Chloroquine Phosphate Tablets
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Determine all-cause mortality up to 28 days after randomization of Chloroquine Phosphate Compared to Chloroquine Phosphate plus Losartan in Non-Critically Ill Patients with SARS-CoV-2 Pneumonia.

Measure: Overall mortality

Time: 28 days

Secondary Outcomes

Description: Compare the clinical outcome of Chloroquine Phosphate treatment vs Chloroquine Phosphate plus Losartan in the follow-up visit at the end of treatment. Acording to NIH and FDA definitions

Measure: Clinical outcome assessment

Time: 28 days

Description: Assess the adverse events associated to chloroquine and chloroquine plus losartan at 28 days

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Time: 28 days

Description: Time to negative Polymerase chain reaction (PCR) test from baseline: testing every 48hrs until a negative result

Measure: Time to negative SARS-CoV-2 test

Time: 28 days
235 A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, Tolerability, Biomarkers and Pharmacokinetics of Ibudilast (MN-166) in COVID-19 Subjects at Risk for Developing Acute Respiratory Distress Syndrome

The study aims to evaluate MN-166 (ibudilast) in patients with COVID-19 who are at risk of developing acute respiratory distress syndrome. Subjects will be screened, randomly assigned to MN-166 or placebo groups, receive study drug on Days 1-7, and followed up on Day 14 and Day 28.

NCT04429555
Conditions
  1. Pneumonia, Viral
Interventions
  1. Drug: Ibudilast
  2. Drug: Placebo
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirements (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 7

Measure: Proportion of subjects free from respiratory failure

Time: 7 days

Description: Mean change from baseline in clinical status based on the NIAID 8-point scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.

Measure: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 7

Time: 7 days

Description: Percentage of patients with at least a one-point improvement in clinical status using the NIAID 8-point ordinal scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.

Measure: Percentage of patients with improvement in clinical status

Time: 7 days

Description: Mean change from baseline (baseline = 1-fold; any value above 1.0 indicates elevation in cytokine levels; any value below 1.0 indicates reduction in cytokine levels) in migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) at Day 7.

Measure: Change in cytokine levels from baseline

Time: 7 days

Secondary Outcomes

Description: Incidence, frequency, and severity of adverse events at Day 7 and Day 14

Measure: Adverse event Incidence, severity, relationship to study drug, and study discontinuations

Time: Days 7, 14

Description: Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.

Measure: Changes in laboratory values from baseline

Time: 7 days

Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14

Measure: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14

Time: 14 days

Description: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 14 and Day 28

Measure: Mean change from baseline in clinical status

Time: Days 14, 28

Description: Proportion of subjects receiving mechanical ventilation or intubation.

Measure: Incidence of mechanical ventilation or intubation

Time: Days 7, 14

Description: Proportion of subjects requiring submission to the intensive care unit

Measure: Intensive care unit admission

Time: 7 days

Description: Blood sample collection to determine plasma concentrations of ibudilast.

Measure: Plasma concentrations of Ibudilast

Time: 7 days

Description: Number of deaths from any cause

Measure: All cause mortality

Time: Days 7, 14, 28
236 Treatment of Severe and Critical COVID-19 Pneumonia With Convalescent Plasma

Open label two arms, non randomized Convalescent Plasma treatment to severe and critical pneumonia COVID-19 hospitlaized patients compared to a historical cohort with matched controls.

NCT04432103
Conditions
  1. Covid-19
Interventions
  1. Biological: Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients
  2. Biological: Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients
MeSH:Pneumon Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: progression to critical stage

Measure: INCIDENCE OF CRITICAL PNEUMONIA

Time: 14 days after convalescent plasma administration

Description: mortality

Measure: MORTALITY RATE AMONG CRITICAL PNEUMONIA PATIENTS

Time: 28 days after convalescent plasma administration

Secondary Outcomes

Description: time to need mechanical ventilation

Measure: INCIDENCE OF MECHANICAL VENTILATION

Time: 14 days after convalescent plasma treatment

Description: time of mechanical ventilation needed

Measure: DAYS OF MECHANICAL VENTILATION

Time: 28 days after convalescent plasma treatment
237 Comparison Between a Pocket Sized and a High End Ultrasound Scanner in the Evaluation of Lung Involvement in Patients With Covid-19 Pneumonia

Ultrasound imaging of the lung (LUS) and associated tissues has demonstrated clinical utility in COVID-19 patients. The aim of the present study was to evaluate the possibilities of a portable pocket-sized ultrasound scanner in the evaluation of lung involvement in patients with COVID-19 pneumonia, in comparison with a high end ultrasound scanner. Statisical analysis will be performed with Stata for Windows V 16 (Stata corp, Texas College, TX). Power size estimation using Medcalc 19.3.1, (MedCalc Software Ltd, Ostenda, B) showed that hat 34 patients would be required for the comparison of the two methods using the Bland-Altman method assuming a mean difference in total score of 1±1, a false positive rate (α) of 0.05 and a false negative rate of 0.1 (β=0.9).

NCT04433000
Conditions
  1. Covid-19 Pneumonia
Interventions
  1. Diagnostic Test: Butterfly
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The more widely accepted measure of agreement beteen two instruments. Bland JM, Altman DG (1986) Statistical method for assessing agreement between two methods of clinical measurement. The Lancet i:307-310

Measure: Bland-Altman estimate of bias and Limits of Agreement (LoA) of patient mean scores obtained with the two instruments

Time: 1 day
238 A Randomized, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of Once Weekly Subcutaneous Injections of Pemziviptadil (PB1046), a Sustained-Release VIP (Vasoactive Intestinal Peptide) ANalogue, in Hospitalized COVID-19 Patients at HiGh Risk for Rapid Clinical Deterioration and ARDS (PB1046 VANGARD Study)

This is a multicenter, randomized, double-blind, parallel group study to investigate the efficacy of pemziviptadil (PB1046) by improving the clinical outcomes in hospitalized COVID-19 patients at high risk for rapid clinical deterioration, acute respiratory distress syndrome (ARDS) and death. The study will enroll approximately 210 hospitalized COVID-19 patients who require urgent decision-making and treatment at approximately 20 centers in the United States.

NCT04433546
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Coronavirus
  3. Hypoxic Respiratory Failure
  4. Hypoxemic Respiratory Failure
  5. Respiratory Complication
  6. Respiratory Insufficiency
  7. Cardiac Dysfunction
  8. Pneumonia
  9. Pulmonary Edema
  10. Pulmonary Inflammation
  11. Respiratory Failure
  12. Cytokine Storm
  13. COVID 19
  14. SARS-CoV-2
  15. Cardiac Event
  16. Cardiac Complication
  17. Cardiac Failure
  18. Cardiac Infarct
Interventions
  1. Drug: Pemziviptadil (PB1046)
  2. Drug: Low Dose (10 mg) Control
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Pulmonary Edema Pulmonary Valve Insufficiency Heart Failure Syndrome Inflammation Clinical Deterioration
HPO:Abnormal left ventricular function Congestive heart failure Pneumonia Pulmonary edema Pulmonary insufficiency Right ventricular failure

Primary Outcomes

Measure: Time to clinical recovery from initiation of pemziviptadil (PB1046)

Time: 28 days

Secondary Outcomes

Measure: Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)

Time: 28 days

Measure: Time to hospital discharge

Time: Any time point between injection initiation and Day 28

Measure: All-cause mortality

Time: 28 days

Description: Composite of: Total hospital days, Total ICU days, Total days of ventilator use, Total days of ECMO, Total days of invasive hemodynamic monitoring, Total days of mechanical circulatory support, Total days of inotropic or vasopressor therapy

Measure: Reduction in hospital resource utilization defined as a composite of: total days: in hospital, in ICU, on ventilator, on ECMO, with invasive hemodynamic monitoring, with mechanical circulatory support, and with inotropic or vasopressor therapy

Time: 28 days

Measure: Time to clinical improvement as defined by reduction of at least 2 points on an 8-category ordinal scale of clinical improvement or discharge from hospital, whichever comes first.

Time: Any time point between injection initiation and Day 28

Measure: Change from baseline in cardiac marker troponin I (TrI)

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in cardiac marker NT-proBNP/BNP

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in TNF alpha

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in IL-1

Time: Any time point between injection initiation and Day 35+7

Measure: Change from baseline in IL-6

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by clinical adverse events (AEs) and their relationship to pemziviptadil (PB1046).

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by vital signs and their relationship to pemziviptadil (PB1046)

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by laboratory results and their relationship to pemziviptadil (PB1046)

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by electrocardiogram (ECG) abnormalities and their relationship to pemziviptadil (PB1046)

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by incidence of anti-drug antibodies and their relationship to pemziviptadil (PB1046)

Time: Any time point between injection initiation and Day 35+7

Other Outcomes

Measure: Impact on invasive hemodynamic parameters as measured by pulmonary artery pressure if patients require right-heart catherization

Time: Any time point between injection initiation and Day 35+7

Measure: Impact on invasive hemodynamic parameters as measured by cardiac output if patients require right-heart catherization

Time: Any time point between injection initiation and Day 35+7

Measure: Incidence of multi-system organ failure (MSOF)

Time: Any time point between injection initiation and Day 35+7

Measure: Number of multi-system organ failure (MSOF) free days

Time: Any time point between injection initiation and Day 35+7

Measure: Number of subjects requiring extracorporeal membrane oxygenation (ECMO)

Time: Any time point between injection initiation and Day 35+7

Measure: Change in circulating ferritin

Time: Any time point between injection initiation and Day 35+7

Measure: Change in circulating D-dimer

Time: Any time point between injection initiation and Day 35+7

Measure: Change in liver function

Time: Any time point between injection initiation and Day 35+7

Measure: Change in other blood chemistry

Time: Any time point between injection initiation and Day 35+7

Measure: Change in hematology

Time: Any time point between injection initiation and Day 35+7

Measure: Change in inflammatory markers

Time: Any time point between injection initiation and Day 35+7

Measure: Change in coagulation markers

Time: Any time point between injection initiation and Day 35+7

Measure: Percent of clinical failure

Time: Any time point between injection initiation and Day 35+7
239 Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19 (RESCUE 1-19): A Randomized Phase III of Best Supportive Care +/- Whole Lung Low-Dose Radiation Therapy in Hospitalized Patients

This phase III trial compares low dose whole lung radiation therapy to best supportive care plus physicians choice in treating patients with COVID-19 infection. Low dose whole lung radiation therapy may work better than the current best supportive care and physician's choice in improving patients' clinical status, the radiographic appearance of their lungs, or their laboratory blood tests.

NCT04433949
Conditions
  1. Pneumonia
  2. Severe Acute Respiratory Syndrome
  3. Symptomatic COVID-19 Infection Laboratory-Confirmed
Interventions
  1. Other: Best Practice
  2. Radiation: Low Dose Radiation Therapy
MeSH:Laboratory Infection Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Will be measured by improvements on oxygenation need prior to intervention compared with after intervention and/or hospital discharge.

Measure: Time to clinical recovery

Time: Up to follow-up day 14 after study start

Secondary Outcomes

Description: The rates from both cohort will be reported.

Measure: Freedom from ICU admission

Time: Up to follow-up day 14 after study start; This may be extended up to 28 days after preplanned interim analysis.

Description: Temperature in degrees (F)

Measure: Temperature

Time: Up to follow-up day 14 after study start

Description: Heart rate in beats per minutes

Measure: Heart rate

Time: Up to follow-up day 14 after study start

Description: Systolic blood pressure in mm Hg

Measure: Systolic Blood pressure

Time: Up to follow-up day 14 after study start

Description: Oxygen saturation in percentage

Measure: Oxygen saturation

Time: Up to follow-up day 14 after study start

Description: Oxygen saturation in percentage

Measure: Supplemental oxygenation need

Time: Up to follow-up day 14 after study start

Description: Respiratory rate in breaths per minute.

Measure: Respiratory rate

Time: Up to follow-up day 14 after study start

Description: Pre and post intervention; Minimum of 3 (poor) to best (15)

Measure: Glasgow Comma Scale from minimum of 3 to maximum of 15.

Time: Up to follow-up day 14 after study start

Description: Easter Cooperative Oncology Group (ECOG) Performance Status Scale from 0-5; 0 being best; 5 being dead;

Measure: Performance status

Time: Up to follow-up day 14 after study start

Description: Survival in percentage

Measure: Survival

Time: Up to follow-up day 14 after study start; This may be extended to 28 days after preplanned interim analysis.

Description: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.

Measure: Serial chest x-rays severe acute respiratory syndrome (SARS) scoring

Time: Up to follow-up day 14 after study start;

Description: CT scans with volume of consolidation measured in cubic centimeters.

Measure: Changes on computed tomography (CT) scans pre and post RT

Time: Baseline up to follow-up day 14 after study start

Description: C-Reactive Protein in mg/L

Measure: CRP

Time: Up to follow-up day 14 after study start

Description: Will be summarized descriptively.

Measure: Serum chemistry + complete blood cell (CBC) with differential

Time: Up to follow-up day 14 after study start

Description: pH (no unit)

Measure: Blood gases pH(when available)

Time: Up to follow-up day 14 after study start

Description: Albumin in gm/dL

Measure: Albumin

Time: Up to follow-up day 14 after study start

Description: Procalcitonin in ng/mL

Measure: Procalcitonin

Time: Up to follow-up day 14 after study start

Description: Asparatate Aminotransferase in units/L

Measure: Aspartate aminotransferase (AST)

Time: Up to follow-up day 14 after study start

Description: Creatinine in mg/dL

Measure: Creatine kinase

Time: Up to follow-up day 14 after study start

Description: Coagulation pathway time in seconds

Measure: Prothrombin time (PT)/partial thromboplastin time (PTT)

Time: Up to follow-up day 14 after study start

Description: Troponin-I in ng/mL

Measure: Troponin

Time: Up to follow-up day 14 after study start

Description: Lactic Acid in mmol/L

Measure: Lactate

Time: Up to follow-up day 14 after study start

Description: B-Natriuretic Peptid in pg/mL

Measure: NT-pBNP (cardiac injury)

Time: Up to follow-up day 14 after study start

Description: Gamma-glutamyl transferase in units/L

Measure: Gamma-glutamyl transferase (GGT)

Time: Up to follow-up day 14 after study start

Description: Trygliciericdes in mg/dL

Measure: Triglycerides

Time: Up to follow-up day 14 after study start

Description: Fibrinogen in mg/dL

Measure: Fibrinogen

Time: Up to follow-up day 14 after study start

Description: Will be summarized descriptively.

Measure: Changes in CD8 T cells

Time: Up to follow-up day 14 after study start

Description: Will be summarized descriptively.

Measure: Changes in CD4 T cells

Time: Up to follow-up day 14 after study start

Description: Will be summarized descriptively.

Measure: Changes in serum antibodies against COVID-19 epitope

Time: Up to follow-up day 14 after study start

Description: Lactate Dehydrogenase in units/L

Measure: LDH

Time: Up to follow-up day 14 after study start

Description: D-Dimer in ng/mL

Measure: D-Dimer

Time: Up to follow-up day 14 after study start

Description: Interleukin-6 in pg/mL

Measure: IL-6

Time: Up to follow-up day 14 after study start

Description: Myoglobin in ng/mL

Measure: Myoglobin

Time: Up to follow-up day 14 after study start

Description: Potassium in mmol/L

Measure: Potassium

Time: Up to follow-up day 14 after study start

Description: Ferritin in ng/mL

Measure: Ferritin

Time: Up to follow-up day 14 after study start

Description: Alanine Aminotransferase in units/L

Measure: ALT

Time: Up to follow-up day 14 after study start
240 Lipid Metabolism in COVID-19 Severe Pneumonia Compared With Severe Pneumonia Caused by Other Pathogen

SARS-COV 2 infection might be responsible for sever pneumonia. Obesity seems to be a risk factor for severe SARS-COV 2 pneumonia. Lipid metabolism alteration are described with both obesity and sepsis. The aim of the present study was to describe association between lipid metabolism, obesity, sepsis inflammation and clinical outcome in COVID-19 patient with severe pneumonia compared with severe pneumonia caused by other pathogenes.

NCT04435223
Conditions
  1. COVID-19 Severe Pneumonia
  2. Severe Pneumonia Due to Other Pathogene
Interventions
  1. Biological: biological assays in particular on the lipid metabolism
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Cholesterol concentration

Time: Within 48 hours following hospital admission

Secondary Outcomes

Description: Ventilator free days (28 days)

Measure: LDL cholesterol / HDL cholesterol/ Lipoprotein size and composition/ Non esterified Fatty acid/ Triglyceridemia/ CETP and PLTP activity/ apolipoprotein canceration/ lipid peroxidation/ Pro and anti inflammatory profile.

Time: Within 48 hours following hospital admission
241 SequelaeCov: a Prospective Study on Lung Damage Caused by SARS-CoV-2 Pneumonia

Pneumonia is a recurrent element of COVID-19 infection, it is often associated with development of respiratory failure and patients frequently need various degrees of oxygen therapy up to non invasive ventilation (NIV-CPAP) and invasive mechanical ventilation (IMV). Main purpose of this study is to evaluate with non invasive clinical instruments (pletysmography, Diffusion lung capacity for carbon monoxide -DLCO-, six minute walking test and dyspnea scores) and radiological tools (chest X-ray and chest CT scan) the development of medium-to-long term pulmonary sequelae caused by SARS-CoV-2 pneumonia.

NCT04435327
Conditions
  1. COVID
  2. Pneumonia, Viral
  3. Barotrauma
  4. Interstitial Lung Disease
  5. Bronchiectasis Adult
  6. Emphysema
MeSH:Pneumonia, Viral Pneumonia Lung Diseases Bronchiectasis Lung Diseases, Interstitial Emphysema Barotrauma
HPO:Abnormal lung morphology Abnormal pulmonary Interstitial morphology Bronchiectasis Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Reduction below 80% of predicted values of DLCO

Measure: Reduction of Diffusion of Lung CO (DLCO, single breath technique)

Time: T1 at 6 months from discharge

Description: Reduction below 80% of predicted values of DLCO

Measure: Reduction of Diffusion of Lung CO (DLCO, single breath technique)

Time: T2 at 12 months from discharge

Secondary Outcomes

Description: reduction in maximum distance walked

Measure: Alterations in 6 minute walking test (6MWT)

Time: T1 at 6 months from discharge

Description: reduction in maximum distance walked

Measure: Alterations in 6 minute walking test (6MWT)

Time: T2 at 12 months from discharge

Description: reduction in oxygen saturation nadir

Measure: Alterations in 6 minute walking test (6MWT)

Time: T1 at 6 months from discharge

Description: reduction in oxygen saturation nadir

Measure: Alterations in 6 minute walking test (6MWT)

Time: T2 at 12 months from discharge

Description: reduction of Forced Vital Capacity (FVC, %)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Forced Vital Capacity (FVC, %)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Forced Vital Capacity (FVC, L)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Forced Vital Capacity (FVC, L)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Vital Capacity (VC, %)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Vital Capacity (VC, %)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Vital Capacity (VC, L)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Vital Capacity (VC, L)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, L)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, %)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, L)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, L%)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Total Lung Capacity (TLC, L)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Total Lung Capacity (TLC, %)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: reduction of Total Lung Capacity (TLC, L)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of Total Lung Capacity (TLC, %)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: alterations of Residual Volume (RV,%)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: alterations of Residual Volume (RV, L)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: alterations of Residual Volume (RV, L)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: alterations of Residual Volume (RV, %)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: increase of Specific Airway Resistance (sRAW) (absolute value)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: increase of Specific Airway Resistance (sRAW) (%)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: increase of Specific Airway Resistance (sRAW) (absolute value)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: increase of Specific Airway Resistance (sRAW) (%)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: alterations of Motley Index (VR/CPT)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: alterations of Motley Index (VR/CPT)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: alterations of Tiffeneau Index (IT)

Measure: Alterations of pletismography

Time: T1 at 6 months from discharge

Description: alterations of Tiffeneau Index (IT)

Measure: Alterations of pletismography

Time: T2 at 12 months from discharge

Description: reduction of PaO2 mmHg

Measure: Alterations of Arterial Blood Gas Analysis

Time: T1 at 6 months from discharge

Description: reduction of PaO2 mmHg

Measure: Alterations of Arterial Blood Gas Analysis

Time: T2 at 12 months from discharge

Description: alteration of PaCO2 mmHg

Measure: Alterations of Arterial Blood Gas Analysis

Time: T1 at 6 months from discharge

Description: alteration of PaCO2 mmHg

Measure: Alterations of Arterial Blood Gas Analysis

Time: T2 at 12 months from discharge

Description: Modified Medical Research Council - mMRC > 0 (minimum 0, maximum 4; higher score means worse outcome)

Measure: Abnormal Dyspnea Score

Time: T1 at 6 months from discharge

Description: Modified Medical Research Council - mMRC > 0(minimum 0, maximum 4; higher score means worse outcome)

Measure: Abnormal Dyspnea Score

Time: T2 at 12 months from discharge

Description: Presence and extension of abnormal pulmonary lung sounds at auscultation

Measure: Presence and extension of abnormal pulmonary lung sounds at auscultation

Time: T1 at 6 months from discharge

Description: Presence and extension of abnormal pulmonary lung sounds at auscultation

Measure: Presence and extension of abnormal pulmonary lung sounds at auscultation

Time: T2 at 12 months from discharge

Description: Presence and extension of radiological alterations at chest X-ray

Measure: Presence and extension of radiological alterations at chest X-ray

Time: T1 at 6 months from discharge

Description: Presence and extension of radiological alterations at chest CT scan

Measure: Presence and extension of radiological alterations at chest CT scan

Time: T2 at 12 months from discharge
242 Uncovering the Cardiac Phenotype of Individuals With SARS-COV-2 and Cardiac Injury

At the end of December of 2019, a series of patients in Wuhan, China were struck with a mysterious respiratory infection. These isolated events have rapidly grown into a deadly, global pandemic. This pandemic is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which results in the Coronavirus Disease 2019 (COVID-19). For individuals infected with COVID-19, approximately 30% of the hospitalized cases are associated with cardiovascular complications. Data are emerging that individuals with pre-exiting conditions (like hypertension, diabetes, cancer, or medical issues related to the immune system) are most susceptible to complications related to COVID-19. Furthermore, individuals of certain racial and ethnic backgrounds (e.g. African American and Hispanic) are at a higher risk of death from COVID-19. Despite these emerging observations, it remains unclear who will develop the cardiovascular complications (acute myocardial injury with evidence of a myocarditis-like picture and cardiogenic shock) and what the long term sequelae of this disease will be for survivors of this infection after hospitalization. Thus, the goals of this project are to better understand the epidemiology of cardiac injury in acutely ill COVID-19 patients through deep cardiac phenotyping and identify the molecular profile of individuals most susceptible to cardiac injury from COVID-19.

NCT04435457
Conditions
  1. SARS-CoV 2
  2. SARS Pneumonia
  3. COVID-19
  4. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
  5. Cardiac Complication
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Patterns of late gadolinium enhancement and T1 and T2 mapping consistent with myocarditis on a post-hospitalization cardiac magnetic resonance imaging examination

Measure: Prevalence of Myocarditis

Time: Up to 4 weeks

Secondary Outcomes

Description: This includes categorically abnormal structural, mechanical functional, vascular, and metabolic using cardiac magnetic resonance imaging

Measure: Prevalence of cardiac abnormalities by cardiac magnetic resonance imaging

Time: Up to 4 weeks

Description: Presence of cardiac autoantibodies and defects within the immune system as detected by Whole Exome Sequencing making an individual susceptible to subacute cardiac injury during COVID-19 infection

Measure: Prevalence of molecular and genetic immune system abnormalities

Time: Up to 4 weeks
243 Treatment of COVID-19 Pneumonia With Glucocorticoids. A Randomized Controlled Trial

Around 30% of admitted patients with COVID-19 pneumonia develop a hyper-inflammatory state whose progression to an acute respiratory distress syndrome (ARSD) could be prevented by the early initiation of immune-modulatory agents. The role of glucocorticoids (GC) in this setting remains controversial. This study aims to assess the safety and effectiveness of GC pulses to improve the clinical outcomes of patients with COVID-19 pneumonia with risen inflammatory biomarkers.

NCT04438980
Conditions
  1. Covid-19 Pneumonia
Interventions
  1. Drug: Methylprednisolone
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: • Death

Measure: Proportion of patients developing treatment failure

Time: At 14 days after randomization

Description: • Need for admission in an intensive care unit (ICU)

Measure: Proportion of patients developing treatment failure

Time: At 14 days after randomization

Description: • Need for mechanical ventilation

Measure: Proportion of patients developing treatment failure

Time: At 14 days after randomization

Description: • Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment

Measure: Proportion of patients developing treatment failure

Time: At 14 days after randomization

Secondary Outcomes

Measure: Mortality at day 28

Time: At 28 days after randomization

Measure: Proportion of patients requiring ICU admission

Time: At 28 days after randomization

Measure: Proportion of patients requiring rescue-therapy with tocilizumab

Time: At 14 days after randomization

Description: Time in days from randomization until the date of hospital discharge.

Measure: Length of hospital stay

Time: At 28 days after randomization

Description: Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant

Measure: Proportion of severe adverse events

Time: At 28 days after randomization

Measure: Proportion of bacterial, fungal or opportunistic infections

Time: At 28 days after randomization

Description: Change in plasma levels of C-reactive protein (CRP)

Measure: Evolution of inflammatory biomarkers related to COVID-19

Time: At 14 days after randomization

Description: Change in plasma levels of ferritin

Measure: Evolution of inflammatory biomarkers related to COVID-19

Time: At 14 days after randomization

Description: Change in plasma levels of interleukin-6 (IL-6)

Measure: Evolution of inflammatory biomarkers related to COVID-19

Time: At 14 days after randomization

Description: Change in plasma levels of lactate dehydrogenase (LDH)

Measure: Evolution of inflammatory biomarkers related to COVID-19

Time: At 14 days after randomization

Description: Change in plasma levels of D-dimer (DD)

Measure: Evolution of inflammatory biomarkers related to COVID-19

Time: At 14 days after randomization

Description: Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum

Measure: Proportion of SARS-CoV-2 clearance.

Time: At 7 days after randomization
244 Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)

This is a randomized, double-blind, placebo-controlled, multicenter, 28-day study of adult participants hospitalized with COVID-19, with a safety follow-up telephone call at Day 60.

NCT04439071
Conditions
  1. Pneumonia
  2. COVID-19
  3. Coronavirus
Interventions
  1. Drug: PTC299
  2. Other: SOC
  3. Drug: Placebo
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Respiratory improvement is defined as sustained peripheral oxygen saturation (SpO2) ≥94% on room air.

Measure: Time from Randomization to Respiratory Improvement

Time: up to Day 28

Secondary Outcomes

Measure: Percentage of Participants Requiring Invasive Ventilation

Time: up to Day 28

Measure: Percentage of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants who did not Require Supplemental Oxygen at Baseline

Time: up to Day 28

Measure: Time from Randomization to Defervescence in Participants Presenting With Fever at Enrollment (Temperature of ≥37.6℃ Axilla, ≥38.0℃ Oral, or ≥38.6°C Tympanic or Rectal)

Time: up to Day 28

Measure: Time from Randomization to Respiratory Rate ≤ 24 Breaths per Minute on Room Air

Time: up to Day 28

Description: Cough will be rated on a scale of severe, moderate, mild, absent, in those with cough at enrollment rated severe or moderate.

Measure: Time from Randomization to Cough Reported as Mild or Absent

Time: up to Day 28

Description: Dyspnea will be rated on a scale of severe, moderate, mild, absent, in those with dyspnea at enrollment rated as severe or moderate.

Measure: Time from Randomization to Dyspnea Reported as Mild or Absent

Time: up to Day 28

Measure: Reduction of Immune Responses

Time: up to Day 28

Measure: Reduction in Viral Load

Time: up to Day 28

Measure: Duration of Hospitalization

Time: up to Day 28

Measure: Number of Mortalities

Time: Day 28

Measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Time: up to Day 28
245 Assessment of Lung Inflammation With FDG PET/CT in COVID-19

The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. Patients admitted with COVID-19 from March 27th to May 3rd, 2020 were prospectively enrolled. All patients had an initial chest CT-scan for diagnosis on admission and a second chest CT-scan for follow-up concomitant with a FDG PET/CT between day 6 and day 14 after the onset of symptoms.

NCT04441489
Conditions
  1. COVID-19
  2. FDG PET/CT
  3. Inflammation
MeSH:Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Amount of FDG pathological uptake expressed by maximum signal intensity standardized uptake values (SUVmax)

Measure: Primary endpoint

Time: Day 6 to Day 14
246 Identification of Predictors for the Evolution of COVID-19 Related Interstitial Pneumonia by Transcriptomic and Seroproteomic Techniques

The investigating group aims at performing an observational, prospective study that involves the evaluation of circulating biomarkers predictive of clinical evolution in patients suffering from COVID-19 disease. In particular, the aim will be to verify whether there are transcripts or cytokines / chemokines in peripheral blood, modulated differently in patients with COVID-19, distinguished on the basis of the evolution towards more severe clinical pictures that require patient intubation or that show signs of cardiovascular damage. The study will be based on the transcriptional analysis of the entire genome and serum protein to evaluate the expression of a broad spectrum of cytokines and chemokines. Genome analysis will allow the genotype to be correlated to the identified gene expression profiles.

NCT04441502
Conditions
  1. Covid19
  2. Interstitial Pneumonia
MeSH:Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Identify circulating transcripts (coding and non-coding for proteins) or cytokines and chemokines which, alone or in combination (COVID19_signature), are predictive of adverse events (death, endotracheal intubation) and the prognostic capacity of COVID19_signature in the prediction of adverse events in additional to the use of standard clinical parameters

Measure: Circulating markers for COVID-19 signature

Time: From ICU/ward admission for 8 weeks follow/up

Secondary Outcomes

Description: Evaluate the association of COVID19_signature with adverse cardiovascular events. Adverse cardiovascular events are defined: death from cardiovascular causes, acute coronary syndrome, troponin T levels greater than the ninety-ninth percentile of the upper reference limit, stroke, cardiac arrhythmias, development of heart failure, venous thromboembolism

Measure: COVID-19 signature and adverse cardiovascular events

Time: From ICU/ward admission for 8 weeks follow/up

Description: Evaluate, in a subset of 20 patients, the characteristics of the coagulation pattern with specific tests for thrombin generation and fibrinolysis.

Measure: COVID-19 related coagulation pattern

Time: From ICU/ward admission for 8 weeks follow/up
247 Controlled and Randomized Clinical Trial for Evaluating the Effect of a Supplement of Glycine as Adjuvant in the Treatment of COVID-19 Pneumonia in Patients Initiating Mechanical Ventilation

This study will explore whether a daily supplement of glycine, a substance that has antiinflammatory, cytoprotective, and endothelium-protecting effects, can improve mortality, as well as clinical and biochemical parameters, in patients with severe COVID-19 who initiate mechanical ventilatory support.

NCT04443673
Conditions
  1. COVID-19
  2. SARS-CoV Infection
  3. SARS (Severe Acute Respiratory Syndrome)
  4. SARS Pneumonia
  5. ARDS, Human
  6. Pneumonia, Viral
Interventions
  1. Dietary Supplement: Glycine
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Adult
HPO:Pneumonia

Primary Outcomes

Description: Number of participants who die divided by number of subjects enrolled in the that study group.

Measure: Mortality

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Secondary Outcomes

Description: Number of days spent under mechanical ventilation.

Measure: Days under mechanical ventilation

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Arterial pressure of oxygen divided by inspired fraction of oxygen.

Measure: PaO2/FiO2 ratio

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Plasma concentration of lactate in arterial blood.

Measure: Arterial plasma lactate

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 1β.

Measure: Serum IL-1β

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 2.

Measure: Serum IL-2

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 4.

Measure: Serum IL-4

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 5.

Measure: Serum IL-5

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 6.

Measure: Serum IL-6

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 7.

Measure: Serum IL-7

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 8.

Measure: Serum IL-8

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 10.

Measure: Serum IL-10

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 12 (p70).

Measure: Serum IL-12

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 13.

Measure: Serum IL-13

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interleukin 17A.

Measure: Serum IL-17

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of granulocyte colony stimulating factor.

Measure: Serum G-CSF

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of granulocyte monocyte colony stimulating factor.

Measure: Serum GM-CSF

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of interferon gamma.

Measure: Serum IFN-γ

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of monocyte chemoattractant protein 1 (MCAF).

Measure: Serum MCP-1

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of macrophage inflammatory protein 1β

Measure: Serum MIP-1β

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of tumor necrosis factor alpha.

Measure: Serum TNF-α

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of creatinine.

Measure: Serum creatinine

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of alanine aminotransferase. .

Measure: Serum alanine aminotransferase

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of aspartate aminotransferase. .

Measure: Serum aspartate aminotransferase

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of alkaline phosphatase.

Measure: Serum alkaline phosphatase

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of total bilirubin.

Measure: Serum total bilirubin

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of unconjugated bilirubin.

Measure: Serum unconjugated bilirubin

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of conjugated bilirubin

Measure: Serum conjugated bilirubin

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of C reactive protein.

Measure: Serum C reactive protein

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Blood concentration of hemoglobin.

Measure: Hemoglobin

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of white blood cells per µl blood.

Measure: Total leukocytes

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of neutrophils per µl blood.

Measure: Neutrophils

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of lymphocytes per µl blood.

Measure: Lymphocytes

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of monocytes per µl blood.

Measure: Monocytes

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of eosinophils per µl blood.

Measure: Eosinophils

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of basophils per µl blood.

Measure: Basophils

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Number of platelets per µl blood.

Measure: Platelets

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Time that blood takes to clot.

Measure: Prothrombin time

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Serum concentration of plasminogen activator inhibitor 1 (PAI-1).

Measure: Serum PAI-1

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Sequence Organ Failure Assessment (SOFA) score, composed by assessment of PaO2/FiO2 ratio, Glasgow coma scale, mean arterial pressure, bilirubin, and platelets.

Measure: SOFA score

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

Description: Acute Physiology And Chronic Health Evaluation II (APACHE II) score, composed by assessment of AaDO2 or PaO2, temperature, mean arterial pressure, pH arterial, heart rate, respiratory rate, sodium, potassium, creatinine, hematocrit, white blood cell count, Glasgow coma scale.

Measure: APACHE II score

Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.
248 Ozone Therapy for Patients With COVID-19 Pneumonia: Preliminary Report of a Prospective Case-control Study

The objective is to determine whether the use of ozone autohemotherapy is associated with a decrease in time to clinical improvement

NCT04444531
Conditions
  1. COVID-19 Pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical improvement was defined as a two-point reduction (relative to the patient's status on hospital admission) on a six-point ordinal scale, or discharge alive from the hospital, whichever came first. The six-point scale was as follows: death (6 points); extracorporeal membrane oxygenation or mechanical ventilation (5 points); noninvasive ventilation or high-flow oxygen therapy (4 points); oxygen therapy without need for high-flow oxygen or non-invasive ventilation (3 points); hospital admission without need for oxygen therapy (2 points); and discharged from hospital or reached discharge criteria (1 point). Discharge criteria were as evidence of clinical recovery (normalization of pyrexia, respiratory rate <24 per minute, oxygen saturation >94% on room air, and absence of cough) for at least 72 hours.

Measure: Time to clinical improvement

Time: 28 days

Secondary Outcomes

Description: Clinical improvement was defined as a two-point reduction (relative to the patient's status on hospital admission) on a six-point ordinal scale, or discharge alive from the hospital, whichever came first. The six-point scale was as follows: death (6 points); extracorporeal membrane oxygenation or mechanical ventilation (5 points); noninvasive ventilation or high-flow oxygen therapy (4 points); oxygen therapy without need for high-flow oxygen or non-invasive ventilation (3 points); hospital admission without need for oxygen therapy (2 points); and discharged from hospital or reached discharge criteria (1 point). Discharge criteria were as evidence of clinical recovery (normalization of pyrexia, respiratory rate <24 per minute, oxygen saturation >94% on room air, and absence of cough) for at least 72 hours.

Measure: Rate of patients with Clinical improvement at day 14

Time: 14 days

Description: Clinical improvement was defined as a two-point reduction (relative to the patient's status on hospital admission) on a six-point ordinal scale, or discharge alive from the hospital, whichever came first. The six-point scale was as follows: death (6 points); extracorporeal membrane oxygenation or mechanical ventilation (5 points); noninvasive ventilation or high-flow oxygen therapy (4 points); oxygen therapy without need for high-flow oxygen or non-invasive ventilation (3 points); hospital admission without need for oxygen therapy (2 points); and discharged from hospital or reached discharge criteria (1 point). Discharge criteria were as evidence of clinical recovery (normalization of pyrexia, respiratory rate <24 per minute, oxygen saturation >94% on room air, and absence of cough) for at least 72 hours.

Measure: Rate of patients with Clinical improvement at day 28

Time: 28 days

Measure: Time to a 2-fold decrease of C-protein reactive from baseline

Time: 28 days

Measure: Time to a 2-fold decrease of ferritin from baseline

Time: 28 days

Measure: Time to a 2-fold decrease of Lactate Dehydrogenase from baseline

Time: 28 days

Measure: Time to a 2-fold decrease of D-dimer from baseline

Time: 28 days
249 A Multicentre, Open-label Clinical Trial to Evaluate the Effectiveness and Safety of Intravenous Tocilizumab for Treating Patients With COVID-19 Pneumonia: the BREATH-19 Study

At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia. The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.

NCT04445272
Conditions
  1. COVID-19
Interventions
  1. Drug: Tocilizumab
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Calculate the mean time of intubation

Measure: To calulate the time of intubation

Time: through study completion, and average of 1 month

Description: Calculate the mean time with oxygen therapy

Measure: To calculate the time with oxygen therapy

Time: through study completion, and average of 1 month

Description: Calculate the mean time with Non-invasive mechanical ventilation

Measure: To calculate the time with Non-invasive mechanical ventilation

Time: through study completion, and average of 1 month

Description: Number of patients deaths of the total of patients included

Measure: To evaluate mortality rate

Time: through study completion, and average of 1 month

Secondary Outcomes

Description: To calculate the mean ofPaO2/FiO2

Measure: To calculate respiratory function parameters

Time: through study completion, and average of 1 month

Description: To calculate the mean of levels of oxygen saturation

Measure: To calculate respiratory function parameters

Time: through study completion, and average of 1 month

Description: To calculate the mean of SaO2/FiO2

Measure: To calculate respiratory function parameters

Time: through study completion, and average of 1 month

Description: Evaluate the lung extension of pneumonia

Measure: To evaluate radiological lung extension

Time: through study completion, and average of 1 month

Description: Evaluate the type of lung affection

Measure: To evaluate radiological evolution

Time: through study completion, and average of 1 month

Description: Days of hospitalization in survivors and/or days at ICU throughout the study

Measure: To describe the duration of hospitalization and ICU use

Time: through study completion, and average of 1 month

Description: Percentage of patients with extracorporeal membrane oxygenation

Measure: To evaluate the requirement of additional organ support

Time: through study completion, and average of 1 month

Description: Percentage of patients with molecular adsorbent recirculating system

Measure: To evaluate the requirement of additional organ support

Time: through study completion, and average of 1 month

Description: Percentage of patients with dialysis

Measure: To evaluate the requirement of additional organ support

Time: through study completion, and average of 1 month

Description: Percentage of patients with other support therapy

Measure: To evaluate the requirement of additional organ support

Time: through study completion, and average of 1 month

Description: Analyze the levels of IL-6

Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers

Time: through study completion, and average of 1 month

Description: Incidence of adverse events

Measure: To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

Time: through study completion, and average of 1 month

Description: Incidence of adverse events by dose of Tocilizumab

Measure: To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

Time: through study completion, and average of 1 month

Description: To evaluate the time to RT-PCR virus negativity

Measure: To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity

Time: through study completion, and average of 1 month

Description: Analyze the levels of CRP

Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

Time: through study completion, and average of 1 month

Description: Analyze the levels of procalcitonin (PCT)

Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

Time: through study completion, and average of 1 month

Description: Analyze the levels of ID-dimer

Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

Time: through study completion, and average of 1 month

Description: Analyze the levels of ferritin

Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

Time: through study completion, and average of 1 month

Description: Indicende of serious adverse events

Measure: To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

Time: through study completion, and average of 1 month

Description: Indicende of serious adverse events based on dose of Tocilizumab

Measure: To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

Time: through study completion, and average of 1 month

Description: Indicende of adverse events of special interest based on dose of Tocilizumab

Measure: To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab

Time: through study completion, and average of 1 month

Description: Number of patients deaths of the total of patients included based on dose of Tocilizumab

Measure: To evaluate mortality rate

Time: through study completion, and average of 1 month

Description: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab

Measure: To evaluate respiratory function

Time: through study completion, and average of 1 month

Description: Number of patients deaths of the total of patients included based on severity of disease at the start of the study treatment

Measure: To evaluate mortality rate

Time: through study completion, and average of 1 month

Description: Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment

Measure: To evaluate mortality rate

Time: through study completion, and average of 1 month

Description: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on severity of disease at the start of the study treatment

Measure: To evaluate respiratory function

Time: through study completion, and average of 1 month

Description: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment

Measure: To evaluate respiratory function

Time: through study completion, and average of 1 month
250 Prasugrel in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients

Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence , and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of purinergic receptor P2Y12 inhibitors in pneumococcal pneumonia may improve inflammation and respiratory function in humans. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider a P2Y12 inhibitor for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of P2Y12 inhibitors and the evidence of improvement in respiratory function both in human and experimental pathology. Prasugrel could be considered as an ideal candidate drug for Covid-19 patients because of higher efficacy and limited Interactions with drugs used in the treatment of Sars-CoV2. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with a P2Y12 inhibitor could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs, antibiotics), except for specific contraindications.

NCT04445623
Conditions
  1. COVID19
  2. Thrombosis
Interventions
  1. Drug: Prasugrel Hydrochloride 10 MG Oral Tablet
  2. Drug: Placebo
MeSH:Pneumonia Thrombosis
HPO:Pneumonia

Primary Outcomes

Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected after 7 days of treatment

Measure: P/F ratio at day 7

Time: day 7

Secondary Outcomes

Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected daily for 15 days

Measure: Daily P/F ratio

Time: 15 days

Description: daily need for oxygen supply for 15 days

Measure: Daily need for oxygen supply

Time: 15 days

Description: Number of patients requiring transfer to the intensive care unit (ICU) by treatment arm

Measure: Need for ICU

Time: day 15 and day 30

Description: death by day 15 and day 30 by treatment arm

Measure: Death

Time: 15 day and day 30

Description: Multi-organ failure (MOF) by day 15 and day 30 assessed using sequential organ failure assessment score (SOFA) score (Units 0-4 better outcome, over 30 worse outcome) by treatment arm

Measure: MOF

Time: day 15 and day 30

Description: Number of patients discharged after improvement by day 15 and day 30 by treatment arm

Measure: Discharge

Time: day 15 and day 30

Description: Clinical progression of the disease evaluated by SOFA score (Units 0-6 better outcome, 15-24 worse outcome) by day 15 and day 30

Measure: Clinical progression of the disease SOFA score

Time: day 15 and day 30

Description: Clinical progression of the disease evaluated by Acute Physiology And Chronic Health Evaluation (APACHE II) score (Units 1-5 better outcome, over 30 worse outcome) by day 15 and day 30

Measure: Clinical progression of the disease APACHE II

Time: day 15 and day 30

Description: Number of patients with venous thrombosis/ pulmonary embolism/thrombosis by day 15 and day 30

Measure: Venous thrombosis/ pulmonary embolism/thrombosis

Time: day 15 and day 30

Description: Number of patients requiring computerized tomography (CT) imaging due to worsening of respiratory function by treatment arm

Measure: Need for CT imaging

Time: day 15

Description: Body temperature measured twice daily for 15 days, C°

Measure: Daily Temperature

Time: 15 days

Description: Blood pressure measured twice daily for 15 days, mmHg

Measure: Daily blood pressure

Time: 15 days

Description: Total blood count measured in venous blood for 15 days, Hemoglobin, g/L (cell/mcL

Measure: Daily total blood count Hemoglobin

Time: 15 days

Description: Total blood count measured in venous blood for 15 days, Red Blood cells (cell/mcL)

Measure: Daily total blood count Red Blood Cells

Time: 15 days

Description: Total blood count measured in venous blood for 15 days, Leukocytes (cell/mcL)

Measure: Daily total blood count Leukocytes

Time: 15 days

Description: Total blood count measured in venous blood for 15 days, platelets (cell/mcL)

Measure: Daily total blood count Platelets

Time: 15 days

Description: ALT U/L in venous blood

Measure: Daily indices of organ damage Liver

Time: 15 days

Description: C-reactive protein microg/L in venous blood

Measure: Indices of inflammation C-reactive protein

Time: day 1, 2, 7, 15

Description: PT ratio in venous blood by treatment arm

Measure: Indices of haemostasis PT

Time: day 1, 2, 7,15

Description: progression of lung infiltrates as detected by chest-X-ray by treatment arm

Measure: Daily progression at imaging (chest-X-ray)

Time: 15 days

Description: Major and/or clinically relevant bleeding according to International Society of Thrombosis and Haemostasis (ISTH) bleeding scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.

Measure: Major bleeding

Time: day 1, 2, 7, 15, 30

Description: Total bleeding according to International Society of Thrombosis and Haemostasis (ISTH bleeding) scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.

Measure: Total bleeding

Time: day 1, 2, 7, 15, 30

Description: Number of unexpected changes in clinical or laboratory findings not included in the predefined list of outcomes during treatment. .

Measure: Unexpected clinical or laboratory findings

Time: day 1, 2, 7, 15

Description: D-dimer microg/L in venous blood

Measure: Indices of inflammation D-dimer

Time: day 1, 2, 7, 15

Description: Fibrinogen g/L in venous blood

Measure: Indices of inflammation Fibrinogen

Time: day 1, 2, 7, 15

Description: Interleukin (IL)-6 pg/mL in venous blood by treatment arm

Measure: Indices of inflammation IL-6

Time: day 1, 2, 7, 15

Description: Interleukin (IL)-1 pg/mL in venous blood by treatment arm

Measure: Indices of inflammation IL-1

Time: day 1, 2, 7, 15

Description: serum creatinine micromol/L by treatment arm

Measure: Daily indices of organ damage kidney

Time: 15 days

Description: troponin t ng/L by treatment arm

Measure: Daily indices of organ damage heart

Time: 15 days

Description: aPTT ratio by treatment arm

Measure: Haemostasis aPTT

Time: day 1, 2, 7,15

Description: Vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) % by treatment arm

Measure: Haemostasis VASP PRI

Time: day 1, 2, 7,15

Description: Platelet-leukocytes aggregates % in peripheral by treatment arm

Measure: Haemostasis platelet-leukocytes aggregates

Time: day 1, 2, 7,15
251 Respiratory Mechanics and Gas Exchange in Patients With COVID-19 and Hypoxemic Acute Respiratory Failure: Multicentral Observational Study

Data on respiratory mechanics and gas exchange in acute respiratory failure in COVID-19 patients is limited. Knowledge of respiratory mechanics and gas exchange in COVID-19 can lead to different selection of mechanical ventilation strategy, reduce ventilator-associated lung injury and improve outcomes. The objective of the study is to evaluate the respiratory mechanics, lung recruitability and gas exchange in COVID-19 -associated acute respiratory failure during the whole course of mechanical ventilation - invasive or non-invasive.

NCT04445961
Conditions
  1. SARS Pneumonia
Interventions
  1. Diagnostic Test: Respiratory mechanics measurement
  2. Diagnostic Test: Gas exchange measurement
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: Positive end-expiratory pressure (PEEP) selection at minimum level with maximum static compliance and the highest peripheral capillary oxygen saturation over fraction of inspired oxygen (SpO2/FiO2)

Measure: Optimum positive end-expiratory pressure (PEEP) level

Time: On day 1 during mechanical ventilation

Description: Positive end-expiratory pressure (PEEP) selection at minimum level with maximum static compliance and the highest peripheral capillary oxygen saturation over fraction of inspired oxygen (SpO2/FiO2)

Measure: Optimum positive end-expiratory pressure (PEEP) level

Time: On day 7 during mechanical ventilation

Description: Peripheral capillary oxygen saturation (SpO2) change from 90% after recruitment maneuver (doubled tidal volume for 15 respiratory cycles) - if peripheral capillary oxygen saturation (SpO2) after recruitment maneuver more than 95%-recruitable

Measure: Number of patients with recruitable lung

Time: On day 1 during mechanical ventilation

Description: Peripheral capillary oxygen saturation (SpO2) change from 90% after recruitment maneuver (doubled tidal volume for 15 respiratory cycles) - if peripheral capillary oxygen saturation (SpO2) after recruitment maneuver more than 95%-recruitable

Measure: Number of patients with recruitable lung

Time: On day 7 during mechanical ventilation

Secondary Outcomes

Description: Calculation of the alveolar dead space using end-tidal carbon dioxide measurement and arterial carbon dioxide tension measurement

Measure: Change in alveolar dead space

Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation

Description: Measurement of plethysmogram variability before and during recruitment maneuver

Measure: Change in plethysmogram variability during recruitment maneuver

Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation

Description: Calculation of the arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio using arterial oxygen tension measurement

Measure: Change in arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio

Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation

Description: Positive end-expiratory pressure (PEEP) selection at minimum level with maximum static compliance and the highest peripheral capillary oxygen saturation over fraction of inspired oxygen (SpO2/FiO2)

Measure: Optimum positive end-expiratory pressure (PEEP) level

Time: On day 3, 5, 10, 14, 21 during mechanical ventilation

Description: Driving pressure calculation at different positive end-expiratory pressure (PEEP) levels (8, 10, 12, 14)

Measure: Change in driving pressure with different positive end-expiratory pressure (PEEP) levels

Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation
252 A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).

NCT04447469
Conditions
  1. COVID
Interventions
  1. Drug: mavrilimumab
  2. Other: Placebo
MeSH:Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).

Measure: Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15

Time: Day 15

Description: Mortality rate is defined as the proportion of participants who die.

Measure: Cohort 2: Mortality Rate at Day 15

Time: Day 15

Secondary Outcomes

Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohort 1: Time to Return to Room Air by Day 15

Time: up to Day 15

Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohort 1: Time to 2-point Clinical Improvement by Day 15

Time: up to Day 15

Description: Mortality rate is defined as the proportion of participants who die.

Measure: Cohort 1: Mortality Rate at Day 29

Time: Day 29

Description: Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohort 1: Time to 1-Point Clinical Improvement by Day 15

Time: up to Day 15

Description: Mortality rate is defined as the proportion of participants who die.

Measure: Cohort 2: Mortality Rate at Day 29

Time: Day 29

Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.

Measure: Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15

Time: Day 15

Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO

Measure: Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29

Time: Day 29

Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohorts 1 and 2: Time to Return to Room Air by Day 29

Time: up to Day 29

Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohort 2: Time to 2-point Clinical Improvement by Day 15

Time: up to Day 15

Description: Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29

Time: up to Day 29

Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29

Time: up to Day 29

Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.

Measure: Cohort 1: Respiratory Failure-Free Survival by Day 15

Time: up to Day 15

Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO

Measure: Cohort 1: Respiratory Failure-Free Survival by Day 29

Time: up to Day 29

Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohort 1: Proportion of Participants Who Return to Room Air by Day 15

Time: up to Day 15

Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29

Time: up to Day 29

Description: Mortality rate is defined as the proportion of participants who die.

Measure: Cohort 1: Mortality Rate at Day 15

Time: Day 15

Description: Overall survival is defined as time from date of randomization to the date of death.

Measure: Cohorts 1 and 2: Overall Survival by Day 29

Time: up to Day 29

Description: Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

Measure: Cohorts 1 and 2: Clinical Status Over Time

Time: Days 4, 8, 15, 22, and 29

Measure: Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90

Time: through Day 90
253 A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of M5049 in Hospitalized Participants With COVID-19 Pneumonia

The study will evaluate the safety and efficacy of orally-administered M5049 in COVID-19 pneumonia participants who are hospitalized but not on mechanical ventilation.

NCT04448756
Conditions
  1. Coronavirus Disease 2019
Interventions
  1. Drug: M5049
  2. Drug: M5049
  3. Drug: Placebo
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation

Time: Day 14

Measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious AEs (SAEs)

Time: Day 1 through Day 60

Measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters and Electrocardiogram Findings

Time: Day 1 through Day 28

Secondary Outcomes

Description: A nine point ordinal scale - 0: Uninfected No limitation of activities Limitation of activities Hospitalized, mild disease on, no oxygen therapy Hospitalized, with oxygen by mask or nasal prongs Hospitalized, severe disease: noninvasive ventilation or high flow oxygen Hospitalized, severe disease: intubation and mechanical ventilation Hospitalized, severe disease: ventilation plus additional organ support - example, vasopressors, Extracorporeal membrane oxygenation (ECMO) Death.

Measure: Clinical Status of Participants on a 9-Point Ordinal Scale

Time: Day 1 through Day 60

Description: Normal oxygen exchange in room air.

Measure: Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours on Room Air

Time: Day 1 through Day 28

Description: Percentage of Participants who die for any reason.

Measure: Percentage of Participants With All-Cause Mortality

Time: Day 1 through Day 28

Description: Clinical Deterioration

Measure: Clinical Deterioration: Time to Intensive Care Unit (ICU) Admission

Time: Day 1 through Day 28

Description: Clinical Deterioration

Measure: Clinical Deterioration: Time to Invasive Mechanical Ventilation

Time: Day 1 through Day 28

Description: Clinical Deterioration

Measure: Clinical Deterioration: Time to Non-Invasive Mechanical Ventilation

Time: Day 1 through Day 28

Measure: Total Length of Stay in Intensive Care Unit (ICU)

Time: Day 1 through Day 60

Measure: Total Length of Hospitalization Stay

Time: Day 1 through Day 60

Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation

Time: Day 1 through Day 28

Measure: Percentage Change From Baseline in Inflammatory Biomarkers

Time: Day 1 through Day 28

Measure: Percentage Change From Baseline in Cytokine Biomarkers

Time: Day 1 through Day 28

Description: Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.

Measure: Percentage of Participants With Relapse

Time: Day 5 through Day 60

Description: Percentage or participants who are re-hospitalized for any reason.

Measure: Percentage of Participants who are Re-Hospitalized

Time: Day 5 through Day 60

Description: Only the first 15 participants will be evaluated for Pharmacokinetic parameters.

Measure: Maximum Observed Concentration (Cmax) of M5049

Time: Day 1 and Day 7

Measure: Time to Reach the Maximum Observed Concentration (tmax) of M5049

Time: Day 1 and Day 7

Measure: Terminal Rate Constant (Lambda z) of M5049

Time: Day 1 and Day 7

Measure: Apparent Elimination Half-Life (t1/2) of M5049

Time: Day 1 and Day 7

Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t) of M5049

Time: Day 1 and Day 7

Measure: Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h) of M5049

Time: Day 1 and Day 7

Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity) of M5049

Time: Day 1 and Day 7

Measure: Apparent Total Body Clearance (CL/F) of M5049

Time: Day 1 and Day 7

Measure: Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of M5049

Time: Day 1 and Day 7

Measure: Dose-Normalized Maximum Observed Concentration (Cmax/Dose) of M5049

Time: Day 1 and Day 7

Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t/Dose) of M5049

Time: Day 1 and Day 7

Measure: Dose-Normalized Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049

Time: Day 1 and Day 7

Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity/Dose) of M5049

Time: Day 1 and Day 7

Measure: Accumulation Ratio for Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose [Racc(AUC0- 12h)] of M5049

Time: Day 1 and Day 7

Measure: Accumulation Ratio for Maximum Observed Concentration [Racc(Cmax)] of M5049

Time: Day 1 and Day 7
254 A Multi-center, Open-label, Randomized Parallel Controlled Evaluation on the Efficacy and Safety of BDB-001 Injection in the Treatment of Progressive Severe COVID-19 in Phase II/III

This multi-center, open, randomized study will evaluate the efficacy and safety of BDB-001 injection in severe COVID-19 with severe pneumonia, or acute lung injury/acute respiratory distress syndrome. Patients will be randomized to two treatment arms (Arm A: Conventional treatment + BDB-001; Arm B: Conventional treatment alone).

NCT04449588
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: BDB-001 Injection
  2. Other: Conventional treatment
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Time to recovery of peripheral capillary oxygen saturation (SpO2) from baseline

Time: Baseline to Day 28

Measure: 28-day all-cause mortality rate

Time: Baseline to Day 28

Secondary Outcomes

Measure: Percentage of subjects achieving recovery in SpO2

Time: Baseline to Day 28

Measure: Mean change of PaO2/FiO2

Time: Baseline to Day 28

Measure: Mechanical ventilation time

Time: Baseline to Day 28

Measure: Time of oxygen therapy

Time: Baseline to Day 28

Measure: Lymphocyte count

Time: Baseline to Day 28

Measure: Change in inflammation indicators (CRP or IL-6) from baseline

Time: Baseline to Day 28

Measure: Improvement in body temperature

Time: Baseline to Day 28

Measure: Mean change from baseline in the clinical improvement based on ordinal scale recommended by the WHO R&D Blueprint during treatment period

Time: Baseline to Day 28

Measure: Improvement at Day3, 7, 11 & Day14 based on ordinal scale recommended by the WHO R&D Blueprint during treatment period

Time: Baseline, Day 3, Day 7, Day 11, Day 14

Measure: Time to get categories 1 to 4 in the 8-points ordinal scale

Time: Baseline to Day 28

Measure: Time to attain an improvement of 1 point on the ordinal scale

Time: Baseline to Day 28
255 Early Use of Corticosteroids in Non-critical Patients With COVID-19 Pneumonia (PREDCOVID)

Steroids has shown benefits in COVID19 patients in observational studies. We hypothesized that early use of corticosteroids, low dose, in mild disease, can decrease progression to respiratory failure and death.

NCT04451174
Conditions
  1. COVID-19
Interventions
  1. Drug: Prednisone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation or All-cause Death by Day 28

Time: 28 days
256 Pilot Clinical, Statistical and Epidemiological Study on Efficacy and Safety of Convalescent Plasma for the Management of Patients With COVID-19

The health contingency established against the Severe Acute Respiratory Syndrome associated type 2 Coronavirus (SARS-CoV-2) has promoted a race against the clock for the search on treatment against the disease related with coronavirus (COVID-19). There are no current approved therapeutic options against the virus, although there is a rush for the development of drugs, vaccines and even the passive immunization through plasma from convalescent patients. This passive immunization is made with the administration of antibodies from patients that went through the infectious state of the disease and progress to clinical remission. SARS-CoV-2, and its predecessor SARS-CoV-1, have great similarities between their genes and proteins; tis allow to hypothesize that the antibodies developed against SARS-CoV1 can recognize the antigens of SARS-CoV-2. In this manner, the transfusion of convalescent plasma to patients with the infection brings the probability on eliminating the infection, in this case SARS-CoV-2. There are evidence of this phenomenon observed in previous pandemics caused by SARS-CoV-1, Influenza AH1N1 and Ebola virus. The objective of the study is to develop a therapeutic strategy based on the administration of plasma from patients with COVID-19 with clinical remission to patients that are coursing with the infection. The expected results hopes to establish an effective treatment and satisfactory recovery of patients with COVID-19. Also, we expect to describe the respective antibodies related against the SARS-CoV-2 infection.

NCT04452812
Conditions
  1. COVID-19 Pneumonia
  2. Convalescent Plasma
Interventions
  1. Biological: Convalescent plasma
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Any cause mortality during the first 30 days of treatment

Measure: All-cause mortality

Time: 30 days

Description: Side effects associated with the administration of convalescent plasma

Measure: Side effects

Time: 30 days

Secondary Outcomes

Description: Time to discharge from the ICU

Measure: Length of stay in Intensive Care Unit (ICU)

Time: 14 days

Description: Time for discharge from hospital

Measure: Length of stay in hospitalization

Time: 21 days

Description: Number of days with ventilatory support

Measure: Days of mechanical ventilation

Time: 14 days

Description: change in D-dimer (micrograms/L)

Measure: Inflammatory biomarkers (d-dimer)

Time: 21 days

Description: change in C-reactive protein (milligrams/dL)

Measure: Inflammatory biomarkers (c-reactive protein)

Time: 21 days

Description: Change in LDH (UI/L)

Measure: Inflammatory biomarkers (lactate dehydrogenase)

Time: 21 days

Description: Change in ferritin (nanograms/mL)

Measure: Inflammatory biomarkers (ferritin)

Time: 21 days
257 A Randomized, Double-blind, Placebo-controlled Phase 2 (2a and 2b) Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia

Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunt an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions1-3. Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication in severe cases is observed, neutralising antibody treatment can be very interesting for patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected patients is therefore an interesting therapeutic option currently under evaluation. However, the difficulties of collecting plasma and its safety aspects are not adapted to many patients. A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates and a First In Human study with another fully representative GH-pAb from Xenothera is ongoing in volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1) to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19 induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when administered to patients with COVID-19 induced moderate pneumonia.

NCT04453384
Conditions
  1. SARS Virus
Interventions
  1. Drug: XAV-19
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8

Measure: Phase 2a: XAV-19 antibody titers

Time: Day 8

Description: Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days

Measure: Phase 2a: Adverse events of XAV-19

Time: Day 29

Description: Efficacy is defined by the proportion of patients who die or develop respiratory failure in the two groups of treatment between baseline and Day 15. Patient with respiratory failure will be patient requiring noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation (corresponding to 8-point ordinal scale ≥ 6).

Measure: Phase 2b: Time to weaning of supplemental oxygen.

Time: Day 15

Secondary Outcomes

Description: XAV-19 Antibody titer over the time

Measure: Phase 2a: Pharmacokinetic analysis

Time: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29

Description: The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients

Measure: Phase 2a: Antibody titer between the two groups

Time: day 15

Description: Duration of supplemental oxygen

Measure: Phase 2a: Supplemental oxygen

Time: Day 1 to Day 29

Description: Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen

Measure: Phase 2a: Evaluation of Transfer to intensive care

Time: Day 1 to Day 29

Description: Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1

Measure: Phase 2a: Normalization of Fever

Time: Day 1 to Day 29

Description: Biomarkers : CRP, Ferritin

Measure: Phase 2a: Biomarkers

Time: Day 1 to Day 29

Description: Evaluation of Hospital length of stay

Measure: Phase 2a: Hospital length of stay

Time: Day 1 to Day 29

Description: a) Proportion of patients who die, develop respiratory failure (requiring noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation) between baseline and Day 8, then between baseline and D29

Measure: Phase 2b: Efficacy of XAV-19

Time: Day 8 and Day 29

Description: b) National Early Warning Score (NEWS) at Day 15 and difference in NEWS between baseline and D8 / D15 / D29

Measure: Phase 2b: National Early Warning Score (NEWS)

Time: Day 8, Day 15 and Day 29

Description: c) Clinical status using the 8-point ordinal scale assessed and difference between baseline and D3, D5, D8, D15, and D29

Measure: Phase 2b: clinical status

Time: Day 3, Day 5, Day 8, Day15, and Day 29

Description: d) Time to improvement of one category from admission using the 8-point ordinal scale. This scale is rated 0 to 8 with score 0 being the better score (no clinical impact) and 8 being the worst score (death)

Measure: Phase 2b: Time to improvement

Time: 29 Days

Description: e) Time to first fever normalization (criteria for normalization: temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or tympanic)

Measure: Phase 2b: fever normalization

Time: 29 Days

Description: f) Duration of oxygen therapy

Measure: Phase 2b: Oxygen therapy

Time: 29 Days

Description: g) Comparison of oxygen requirement between the two groups

Measure: Phase 2b: oxygen requirement

Time: 29 Days

Description: h) Time to weaning in supplemental oxygen and proportion without O2 requirement at Day 8, D15 and Day 29, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)

Measure: Phase 2b: Time to weaning

Time: Day8, Day 15 and Day 29

Description: i) Incidence and duration of non-invasive ventilation or high flow oxygen devices, of invasive mechanical ventilation during the study

Measure: Phase 2b: Ventilation

Time: 29 Days

Description: j) Evaluation of hospital length of stay

Measure: Phase 2b: Hospital length of stay

Time: 29 Days

Description: k) All cause mortality

Measure: Phase 2b: mortality

Time: 29 Days

Description: l) Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events Proportion of participants with treatment emergent adverse events leading to study drug discontinuation Incidence of major or opportunistic bacterial or fungal infections Incidence of hypersensitivity reactions and infusion reactions White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D11, D15 and D29 SARS-CoV-2 viral load over time (D1-D29), as collected by nasopharyngeal swab samples Time to RT-PCR virus negativity in nasopharyngeal swab samples

Measure: Phase 2b: safety

Time: 29 Days
258 Interest of Azithromycin With or Without Hydroxychloroquine for the Treatment of COVID-19 Pneumonia : a Retrospective Observational Study

During COVID-19 epidemic, hydroxychloroquine was proposed and authorized as a possible key agent in the treatment of COVID-19 hospitalized pneumonia, including in France. Gautret et al. proposed the combination regimen with azithromycin. However only one study reported the interest of azithromycin alone. Retrospective study reporting the impact of the anti-infective agents used during the pandemic in a tertiary care hospital, using azithromycin with or without hydroxychloroquine.

NCT04453501
Conditions
  1. COVID
  2. Pn
  3. Pneumonia, Viral
Interventions
  1. Drug: favorable outcome
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: After being admitted, patient was monitored whether he does not required to be transferred in ICU or died because of a severe COVID-19 pneumonia within 7 days. The outcome was purely clinical. If patient was discharged at home after admission and/or was transferred into a rehabilitation center he was considered as a favorable outcome independently of any biological marker.

Measure: Favorable outcome

Time: Assessed within 7 days after admission

Secondary Outcomes

Description: Studying if biological abnormalities (lymphocyte count or CRP) at admission were associated with an unfavorable outcome

Measure: Risk factors 1

Time: Assessed at day 1

Description: Studying if comorbidities were associated with an unfavorable outcome

Measure: Risk factors 2

Time: Assessed at day 1

Description: Studying whether any regimen was associated with a favorable outcome (including azithromycin)

Measure: Interest of anti-infective agents

Time: From date of inclusion until the date of first documented progression to ICU or date of death from any cause, whichever came first, assessed up to 2 months
259 Impact of the Syndromic PCR System FilmArray on Management of ICU Patients With Severe Pulmonary Disease in the Context of the Covid-19 Pandemic.

The research aims to determine the impact of a syndromic mutiplex PCR assay (FilmArray) on the management of patients hospitalized in ICU for severe respiratory disease. During the SARS-CoV-2 outbreak, the diagnosis of pneumonia has become considerably more complex as the biological, radiological and clinical criteria of covid-19 interfere with the standard criteria for the diagnosis of severe respiratory diseases. Moreover, patients with COVID-19 are at higher risk of developing other associated infections and thus, patients have therefore often been treated with antibiotics, adequately or not, due to difficulty to quickly identify the etiology of their symptoms with conventional methods. In order to improve their treatment, both diagnostic and therapeutic, we set up a new syndromic molecular test in our laboratories to accelerate and improve the pneumonia management and antibiotic stewardship. This research will include 100 to 150 adult patients hospitalized in ICU during the first half of 2020. It will take place within the Nancy University Hospital and the Reims University Hospital, France.

NCT04453540
Conditions
  1. Infectious Disease
  2. Pneumonia
  3. Molecular Diagnosis
  4. Covid-19
  5. Antibiotic Stewardship
Interventions
  1. Diagnostic Test: FilmArray PCR on respiratory samples
MeSH:Communicable Diseases Infection Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Antibiotic prescription modification following the FilmArray results as: No prescription No change in antibiotic utilization Antibiotic initiation Antibiotic escalation Antibiotic de-escalation Antibiotic discontinuation

Measure: Therapeutic decision

Time: 24 h following the FilmArray results
260 Inhaled NO for the Treatment of COVID-19 Caused by SARS-CoV-2

The purpose of this open label, 2-phase, study is to obtain information on the safety of 80 ppm and the safety and efficacy of 150 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.

NCT04456088
Conditions
  1. COVID-19
  2. SARS-CoV 2
  3. Respiratory Disease
  4. Pneumonia, Viral
  5. Corona Virus Infection
Interventions
  1. Combination Product: 150 ppm Nitric Oxide delivered through LungFit Delivery System
  2. Combination Product: 80 ppm Nitric Oxide delivered through LungFit Delivery System
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiration Disorders Respiratory Tract Diseases
HPO:Pneumonia

Primary Outcomes

Description: Time to deterioration as measured by any one of the following: need for non-invasive ventilation need for high flow nasal cannula (HFNC) or need for intubation Death from any cause

Measure: Time to deterioration

Time: up to 14 days

Secondary Outcomes

Description: Time to patient having stable oxygen saturation (SpO2) of greater than 92% for longer than 3 hr on room air

Measure: Time to stable oxygen saturation

Time: up to 14 days

Other Outcomes

Description: Treatment Emergent Adverse Events and SAEs - safety evaluation for 30 days after last inhalation treatment

Measure: Treatment Emergent Adverse Events and SAEs

Time: 30 days after last inhalation treatment
261 Evaluation of the Characteristics of Patients and Healthcare Workers With Suspected or Confirmed of COVID-19 in Villavicencio and Meta State, Colombia

This observational study aims to collect detailed clinical information on confirmed or suspected patients of COVID-19 treated in hospitals from Meta State, Colombia. The objectives are: 1. To establish the characteristics of patients and healthcare workers treated with COVID-19. 2. To assess previous predisposing morbidity. 3. To detail clinical factors associated with complications. 4. To profile clinical indicators for severity and outcomes.

NCT04456426
Conditions
  1. COVID
  2. SARS-CoV 2
  3. SARS Pneumonia
  4. SARS (Disease)
  5. SARS (Severe Acute Respiratory Syndrome)
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Death within 30 days of hospital admission

Measure: Mortality

Time: 30 days

Description: Need for intensive care unit admission

Measure: ICU admission

Time: 30 days

Description: Need for intubation and invasive mechanical ventilation

Measure: Mechanical ventilation

Time: 30 days

Secondary Outcomes

Description: Duration of stay in the intensive care unit

Measure: ICU length of stay

Time: 30 days

Description: Duration of stay in hospitalization

Measure: Hospital length of stay

Time: 30 days

Description: Duration of mechanical ventilation included with intubation or tracheostomy

Measure: Days of mechanical ventilation

Time: 30 days
262 Risk Factors, Personalized Prognoses and 1-year Follow-ups of Patients Admitted to Spanish Intensive Care Units Due to COVID-19

The latest epidemiological data published from Chine reports that up to 30% of hospital-admitted patients required admission to intensive care units (ICU). The cause for ICU admission for most patients is very severe respiratory failure; 80% of the patients present with severe acute respiratory distress syndrome (SARS) that requires protective mechanical ventilation. Five percent of patients with SARS require extracorporeal circulation (ECMO) techniques. Global mortality data has been thus far reported in different individual publications from China. Without accounting for those patients still admitted to hospital, bona fide information (from a hospital in Wuhan) received by the PI of this project estimates that mortality of hospitalized patients is more than 10%. Evidently, mortality is concentrated in patients admitted to the ICU and those patients who require mechanical ventilation and present with SARS. As data in China was globally reported, risk factors and prognosis of patients with and without SARS who require mechanical ventilation are not definitively known. The efficacy of different treatments administered empirically or based on small, observation studies is also not known. With many still admitted at the time of publication, a recent study in JAMA about 1500 patients admitted to the ICU in the region of Lombardy (Italy) reported a crude mortality rate of 25%. The data published until the current date is merely observational, prospective or retrospective. Data has not been recorded by analysis performed with artificial intelligence (machine learning) in order to report much more personalized results. Furthermore, as it concerns patients admitted to the ICU who survive, respiratory and cardiovascular consequences, as well as quality of living are completely unknown. The study further aims to investigate quality of life and different respiratory and cardiovascular outcomes at 6 months, as well as crude mortality within 1 year after discharge of patients with COVID-19 who survive following ICU admission. Lastly, with the objective to help personalize treatment in accordance with altered biological pathways in each patient, two types of studies will be performed: 1) epigenetics and 2) predictive enrichment of biomarkers in plasma. Hypothesis - A significant percentage of patients (20%) admitted to the hospital with COVID-19 infection is expected to require ICU admission, and need mechanical ventilation (80%) and, in a minor percentage (5%), ECMO. - Patients who survive an acute episode during ICU hospitalization will have a yearly accumulated mortality of 40%. Those who then survive will have respiratory consequences, cardiovascular complications and poor quality of life (6 months).

NCT04457505
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Severe Pneumonia
  3. Respiratory Failure
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury
HPO:Pneumonia

Primary Outcomes

Description: People who died after one year of follow up

Measure: One year mortality

Time: At 12 months of ICU admission

Description: People who died after one year of follow up

Measure: Six month mortality

Time: At 6 month of ICU admission
263 A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Assess Safety and Efficacy of ANG- 3777 in Patients Hospitalized With Confirmed COVID-19 Pneumonia

To assess the clinical efficacy of ANG-3777 relative to the standard of care in reducing the severity and progression of pulmonary and renal dysfunction and mortality in adult patients hospitalized with COVID-19 pneumonia

NCT04459676
Conditions
  1. COVID-19
  2. Pneumonia
Interventions
  1. Drug: Standard of Care (SOC) + ANG-3777
  2. Drug: Standard Of Care (SOC) + Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Proportion of patients alive, without the need for mechanical ventilation and free of the need for RRT (on an ongoing basis) at Day 28

Time: From the time of randomization until (Day 1) until death or until Day28, whichever comes first
264 A Phase IIa Randomized, Controlled Study of Combination Therapies to Treat COVID-19 Infection

This study seeks to determine whether dual or quadruple therapy is more effective in treating COVID-19.

NCT04459702
Conditions
  1. COVID
  2. COVID-19
  3. Corona Virus Infection
  4. Coronavirus Infection
  5. Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere
  6. Coronavirus-19
  7. SARS-CoV 2
  8. SARS Pneumonia
Interventions
  1. Drug: hydroxychloroquine
  2. Drug: Azithromycin
  3. Drug: Ritonavir
  4. Drug: Lopinavir
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.

Measure: Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores

Time: 6 months

Description: Time to non-infectivity as measured by PCR testing

Measure: Efficacy of Treatment by Time to Non-Infectivity

Time: 10 days

Secondary Outcomes

Description: Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.

Measure: Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores

Time: 6 months

Description: Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.

Measure: Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores.

Time: 6 months

Description: Changes in blood parameters measured in a Complete Blood Count (CBC).

Measure: Safety of Dual Therapy as Measured by Complete Blood Count

Time: 6 months

Description: Changes in blood parameters measured in a Complete Metabolic Panel.

Measure: Safety of Quadruple Therapy as Measured by Complete Blood Count

Time: 6 months

Description: Changes in serum albumin levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel -Albumin

Time: 6 months

Description: Changes in serum albumin levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin

Time: 6 months

Description: Changes in serum albumin/globulin ratio

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio

Time: 6 months

Description: Changes in serum albumin/globulin ratio

Measure: Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio

Time: 6 months

Description: Changes in serum alkaline phosphatase levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase

Time: 6 months

Description: Changes in serum alkaline phosphatase levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase

Time: 6 months

Description: Changes in serum AST levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - AST

Time: 6 months

Description: Changes in serum AST levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - AST

Time: 6 months

Description: Changes in serum ALT levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT

Time: 6 months

Description: Changes in serum ALT levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel ALT

Time: 6 months

Description: Changes in serum BUN/Creatinine Ratio

Measure: Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio

Time: 6 months

Description: Changes in serum BUN/Creatinine Ratio

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio

Time: 6 months

Description: Changes in serum Blood Urea Nitrogen levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN

Time: 6 months

Description: Changes in serum Blood Urea Nitrogen levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - BUN

Time: 6 months

Description: Changes in serum calcium levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Calcium

Time: 6 months

Description: Changes in serum calcium levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium

Time: 6 months

Description: Changes in serum carbon dioxide levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide

Time: 6 months

Description: Changes in serum carbon dioxide levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide

Time: 6 months

Description: Changes in serum chloride levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Chloride

Time: 6 months

Description: Changes in serum chloride levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride

Time: 6 months

Description: Changes in serum creatinine levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine

Time: 6 months

Description: Changes in serum creatinine levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine

Time: 6 months

Description: Changes in serum globulin levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Globulin

Time: 6 months

Description: Changes in serum globulin levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin

Time: 6 months

Description: Changes in blood glucose levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose

Time: 6 months

Description: Changes in blood glucose levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Glucose

Time: 6 months

Description: Changes in blood potassium levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Potassium

Time: 6 months

Description: Changes in blood potassium levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium

Time: 6 months

Description: Changes in serum total bilirubin levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin

Time: 6 months

Description: Changes in serum total bilirubin levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin

Time: 6 months

Description: Changes in serum total protein levels

Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein

Time: 6 months

Description: Changes in serum total protein levels

Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein

Time: 6 months

Description: Presence or absence of treatment related serious adverse events Grade III or higher

Measure: Safety of Dual Therapy as Measured by Treatment Related SAE

Time: 6 months

Description: Presence or absence of treatment related serious adverse events Grade III or higher

Measure: Safety of Quadruple Therapy as Measured by Treatment Related SAE

Time: 6 months
265 A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia

The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in adults hospitalized with COVID-19 pneumonia.

NCT04460105
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Lanadelumab
  2. Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.

Measure: Number of Participants with Treatment emergent adverse events (TEAEs)

Time: From start of study drug administration to follow-up (up to Day 29)

Secondary Outcomes

Description: Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.

Measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab

Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose

Description: Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.

Measure: Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)

Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose

Description: Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.

Measure: Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)

Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose

Description: Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.

Measure: Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)

Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose
266 Treatment of Coronavirus COVID-19 Pneumonia (Pathogen SARS-CoV-2) With Cryopreserved Allogeneic Multipotent Mesenchymal Stem Cells of the Placenta and Umbilical Cord

Assessment of the clinical effects of infusions of cryopreserved allogeneic multipotent mesenchymal stem cells of the placenta and umbilical cord for COVID-19 patients with acute respiratory distress syndrome.

NCT04461925
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Procedure: Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells
  2. Drug: Antibiotics
  3. Drug: Hormones
  4. Drug: Anticoagulant Therapy
  5. Device: Оxygen therapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Improvement of pulmonary function. Arterial oxygen tension PaO2 (in mmHg)/fractional inspired oxygen FiO2 (expressed as a fraction, not a percentage), most conveniently the P/F ratio. The normal P/F ratio is ~ 400-500 mmHg (~55-65 kPa). P/F ratio <300mmHg - sign of Acute Respiratory Distress Syndrome (ARDS)

Measure: Changes of oxygenation index PaO2/FiO2, most conveniently the P/F ratio.

Time: up to 28 days

Description: Length of Hospital Stay

Measure: Changes in length of hospital stay

Time: up to 28 days

Description: Marker for efficacy of treatment

Measure: Changes in mortality rate

Time: up to 28 days

Secondary Outcomes

Description: Infection biomarker. Serum CRP levels can be used for early diagnosis of pneumonia, patients with severe pneumonia had high CRP levels.

Measure: Changes of С-reactive protein (CRP, mg/L)

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: CT assessment of pulmonary lesions and lung tissue changes

Measure: Evaluation of Pneumonia Improvement

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Indirect response to lung function

Measure: Duration of respiratory symptoms (difficulty breathing, dry cough, fever, etc.)

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

Description: Degree of infection

Measure: Peripheral blood count recovery time

Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
267 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation

The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

NCT04463004
Conditions
  1. COVID-19
  2. Sars-CoV2
  3. Pneumonia
Interventions
  1. Drug: Mavrilimumab
  2. Drug: Placebos
MeSH:Pneumonia Respiratory Insufficiency Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Number of subjects alive and off of oxygen

Measure: Proportion of subjects alive and off of oxygen at day 14

Time: 14 days

Secondary Outcomes

Description: Number of subjects alive and without respiratory failure

Measure: Proportion of subjects alive and without respiratory failure at 28 days

Time: 28 days
268 Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)

This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.

NCT04466098
Conditions
  1. Acute Respiratory Distress Syndrome
  2. ARDS (Moderate or Severe)
  3. COVID-19 Pneumonia
Interventions
  1. Biological: Mesenchymal stromal cells
  2. Other: Placebo
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Measure: Incidence of grade 3-5 infusional toxicities and predefined hemodynamic or respiratory adverse events related to the infusion of MSC

Time: Within 6 hours of the start of the infusion

Secondary Outcomes

Measure: Incidence of a reduction in one or more biomarkers of inflammation by day 7

Time: Day 7 after first infusion

Measure: Trend changes in PaO2:FiO2 ratio

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Trend changes in Mean Airway Pressure

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Trend changes in peak pressure

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Trend changes in plateau pressure

Time: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion

Measure: Trend changes in Positive end-expiratory airway pressure (PEEP)

Time: On the day of screening and on days 3, 7 and 14 after first infusion

Measure: Incidence of mortality

Time: 28 days after first infusion

Measure: Incidence of mortality

Time: 100 days after first infusion

Measure: Number of ICU-free days

Time: 28 days after first infusion

Measure: Number of days alive and ventilator free composite score 3

Time: 28 days after first infusion

Description: Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph

Measure: Change in acute lung injury (ALI) score 2

Time: Baseline and Day 28 after first infusion

Measure: Incidence of serious adverse events

Time: 28 days after first infusion

Measure: Number of days alive off supplemental oxygen

Time: 100 days after first infusion
269 Phase II Protocol of Low-Dose Whole Thorax Megavoltage Radiotherapy for Patients With SARS-COV-2 Pneumonia

Low doses of radiation in the form of chest x-rays has been in the past to treat people with pneumonia. This treatment was thought to reduce inflammation and was found to be effective without side effects. However, it was an expensive treatment and was eventually replaced with less expensive treatment options like penicillin. The COVID-19 virus has emerged recently, causing high rates of pneumonia in people. The authors believe that giving a small dose of radiation to the lungs may reduce inflammation and neutralize the pneumonia caused by COVID-19. For this study, the x-ray given is called radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat cancers. The purpose of this study is to find out if adding a single treatment of low-dose x-rays to the lungs might reduce the amount of inflammation in the lungs from COVID-19 infection, which could reduce the need for a ventilator or breathing tube.

NCT04466683
Conditions
  1. Covid-19
  2. Sars-CoV2
  3. Pneumonia
Interventions
  1. Radiation: Low dose radiation 35 cGy
  2. Radiation: High dose radiation 100 cGy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The rate of grade 4 toxicity, the rate of mechanical ventilation, the rate of hospital stay greater than 10 days, and the crude all-cause mortality rate will be used to calculate the clinically meaningful event rate (CMER). The rates range would be from 0 to 100% with a lower rate indicating a more favorable dose.

Measure: Step 1 Dose selection

Time: At least 2 weeks after the 60th patient enrolled has been evaluated for adverse events. It is estimated that the time frame will be about 1 year to complete enrollment.

Description: Clinical benefit will have the composite endpoint with the following 3 elements: the rate of mechanical ventilation, the rate of hospital stays of greater than 10 days and the rate of all-cause mortality at 30 from enrollment. A lower rate would indicate a positive clinical benefit and would range from 0 to 100%

Measure: Clinical benefit of Step 2 Radiation dose

Time: up to 30 days from the last patient enrollment in Step 2 which is estimated to be about 2 years.

Secondary Outcomes

Description: Billing codes will be collected to determine the total cost of hospitalization for each patient at discharge. The cost of hospitalization for the control arm versus experimental radiation arms will be compared.

Measure: Changes of the cost of care for the control arm versus the radiation arms

Time: The discharge of the last patient enrolled is estimated to be about 2 years.

Other Outcomes

Description: Compare differences within and between arms lymphocyte count in K/ul.

Measure: Changes in lymphocyte count between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization.

Description: Compare differences within and between arms neutrophil count in K/ul .

Measure: Changes in neutrophil count between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

Description: Compare differences within and between arms for the neutrophil to lymphocyte ratio. A decrease in the ratio of neutrophil to lymphocyte count would indicate a more favorable treatment outcome.

Measure: Changes in neutrophil to lymphocyte ratio between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

Description: Compare differences within and between arms for the C-reactive protein in mg/L. A decrease in C-reactive protein value would indicate a more favorable treatment outcome.

Measure: Changes in blood C-reactive protein between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

Description: Compare differences within and between arms for the IL-6 in pg/ml. A decrease in IL-6 value would indicate a more favorable treatment outcome.

Measure: Changes in blood IL-6 levels between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

Description: Compare differences within and between arms for the D-Dimer in mcg/ml. A decrease in D-Dimer value would indicate a more favorable treatment outcome.

Measure: Changes in blood D-Dimer levels between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

Description: Compare differences within and between arms for the LDH in U/L. A decrease in LDH value would indicate a more favorable treatment outcome.

Measure: Changes in blood Lactate dehydrogenase (LDH) levels between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

Description: Compare differences within and between arms for ferritin in ng/ml. A decrease in Ferritin value would indicate a more favorable treatment outcome.

Measure: Changes in blood ferritin levels between control and experimental arms

Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
270 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2/3 Study, in Adult Subjects Hospitalized With Severe SARS-CoV-2 Positive Pneumonia

A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.

NCT04467840
Conditions
  1. COVID-19
  2. Lung Infection
Interventions
  1. Drug: Opaganib
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To compare the proportion of patients requiring intubation and mechanical ventilation by Day 14 between subjects taking opaganib and those on placebo.

Measure: Intubation and mechanical ventilation

Time: 14 days

Secondary Outcomes

Description: Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.

Measure: WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0

Time: 14 days

Description: To compare the time to intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

Measure: Time to intubation and mechanical ventilation

Time: 14 days

Description: To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.

Measure: Time to low oxygen flow via nasal cannula

Time: 14 days

Description: To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.

Measure: Supplemental oxygen requirement

Time: 14 days

Description: To compare the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days (Day 1 to Day 14) between subjects taking opaganib and those on placebo.

Measure: Total daily oxygen requirement

Time: 14 days

Description: To compare the time to two consecutive negative swabs for SARS-CoV-2 by PCR between subjects taking opaganib and those on placebo.

Measure: Time to negative swabs for SARS-CoV-2

Time: 14 days

Description: To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

Measure: Negative swabs for SARS-CoV-2 at day 14

Time: 14 days

Description: To compare the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C [100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14 between subjects taking opaganib and those on placebo.

Measure: Fever

Time: 14 days

Description: To compare mortality 30 days post-baseline between subjects taking opaganib and those taking placebo

Measure: Mortality

Time: 30 days post baseline

Other Outcomes

Description: To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo

Measure: Adverse events

Time: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment

Description: To compare the change in the systemic marker of inflammation, D-dimer, over the treatment period between subjects taking opaganib and those on placebo.

Measure: Inflammatory markers - D-dimer

Time: 14 days

Description: To compare the change in the systemic marker of inflammation, cardiac troponin, over the treatment period between subjects taking opaganib and those on placebo.

Measure: Inflammatory markers - cardiac troponin

Time: 14 days

Description: To compare the change in the systemic marker of inflammation, C-reactive protein [CRP], over the treatment period between subjects taking opaganib and those on placebo.

Measure: Inflammatory markers - C-reactive protein

Time: 14 days

Description: To compare the change in the systemic marker of inflammation lactate dehydrogenase [LDH] over the treatment period between subjects taking opaganib and those on placebo.

Measure: Inflammatory markers - lactate dehydrogenase

Time: 14 days

Description: To compare the change in the systemic marker of inflammation ferritin over the treatment period between subjects taking opaganib and those on placebo.

Measure: Inflammatory markers - ferritin

Time: 14 days
271 Early Cognitive Assessment and Evolutionary Monitoring of Patients With Severe ARDS (Acute Respiratory Distress Syndrome) on SARS-CoV2 Viral Pneumonia Requiring Mechanical Ventilation

The new coronavirus pandemic responsible for the severe acute respiratory syndrome SARS-CoV2 requires, in its severe forms, the use of invasive ventilation in intensive care. The first patients seen in intensive care presented with neurological symptoms and usually not seen in non-viral ARDS or due to other viral causes. These were mainly restless awakenings, attempts at self-extubation and confusional syndromes. Although the data in the literature do not seem to reveal the presence of SARS-CoV2 in the CSF of these patients, certain elements seem to show parenchymal brain damage with the description of hypometabolism of the frontal regions. In addition, most of these patients present a memory complaint after going into intensive care (personal data not published). We do not know to date what is the cognitive and psychic profile of these patients, nor what will be their future evolution. Some patients may require specific neuro-cognitive rehabilitation. The aim of this study is to assess the cognitive profile of patients infected with COVID-19 who have used invasive ventilation in the intensive care unit of Paris Saint-Joseph hospital since April 2020, in order to be able to compare them between them and follow their evolution in the medium term. This work could make it possible to describe the specific cognitive impairment of SARS-CoV2, by trying to evade other causes of cognitive disorders in patients hospitalized in intensive care for respiratory distress (hypoxia, treatments, metabolic disorders, etc.). The main objective is to follow the medium-term evolution between 3 and 6 months of the cognitive profile of patients with severe form of SARS-CoV2 with the use of ventilatory resuscitation.

NCT04468035
Conditions
  1. Covid19
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: This ouctome corresponds to the medium-term evolution between 3 and 6 months of the cognitive profile of patients with severe form of SARS-CoV2 with recourse to ventilatory resuscitation.

Measure: Medium-term evolution between 3 and 6 months

Time: Month 6

Secondary Outcomes

Description: This outcome corresponds to MMSE orientation score.

Measure: Cognitive impairment at M3

Time: Month 3

Description: This outcome corresponds to MMSE orientation score.

Measure: Cognitive impairment at M6

Time: Month 6

Description: This outcome corresponds to Memory scores.

Measure: Memory Scores at M3

Time: Month 3

Description: This outcome corresponds to Memory scores.

Measure: Memory Scores at M6

Time: Month 6
272 A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia

Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.

NCT04469114
Conditions
  1. Covid19
Interventions
  1. Drug: Tofacitinib 10 mg
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: 1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome). Death. Hospitalized, on invasive mechanical ventilation or ECMO. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, requiring supplemental oxygen. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise). Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care. Not hospitalized, limitation on activities and/or requiring home oxygen. Not hospitalized, with no limitations on activities.

Measure: Death or respiratory failure ate Day 28

Time: 28 days

Secondary Outcomes

Description: NIAID ordinal scale of disease severity

Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14

Time: 14 days

Description: Categories 3 to 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 and Day 28

Measure: Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14

Time: 14 and 28 days

Description: Categories 1 to 4 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity

Measure: Status of requiring supplemental oxygen at Day 28

Time: 28 days

Description: Categories 7 and 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity

Measure: Status of being alive and not hospitalized at Day 14 and 28

Time: 14 and 28 days

Description: NIAID ordinal scale of disease severity

Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28

Time: 28 days

Description: Number of patients with resolution of fever, cough, and need for ventilatory or oxygen support.

Measure: Number of patients with cure

Time: 28 days

Description: Number of patients at the ICU or on ventilatory support

Measure: Number of patients at the ICU or on ventilatory support at Day 28

Time: 28 days

Description: Number of days free from mechanical ventilation

Measure: Number of days free from mechanical ventilation at 28 days

Time: 28 days

Description: Number of days in hospital

Measure: Number of days in hospital

Time: 28 days

Description: Number of days in ICU

Measure: Number of days in ICU

Time: 28 days
273 Assessment of Lung Recruitablity of Acute Respiratory Distress Syndrome With SARS-CoV-2 Pneumonia by Electrical Impedance Tomography: a Prospective Observational Study

Novel coronavirus (SARS-CoV-2: severe acute respiratory coronavirus 2) pneumonia often develop the acute respiratory distress syndrome (ARDS). Lung protective ventilation strategy consisting of low tidal volume and high positive end-expiratory pressure (PEEP) is recommended. However, it is not clear whether injured lungs from SARS-CoV-2 pneumonia have the same mechanical properties, especially response to PEEP as common ARDS. Therefore, the investigators propose an observational study to analyze respiratory mechanics and lung recruitablity using EIT (electrical impedance tomography) in patients with ARDS due to SARS-CoV-2 pneumonia.

NCT04473300
Conditions
  1. Critical Illness
  2. ARDS
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Critical Illness
HPO:Pneumonia

Primary Outcomes

Description: The distribution of ventilation measured by EIT at PEEP 5 and 15.

Measure: The distribution of ventilation

Time: Through study completion (up to 24 hours)

Secondary Outcomes

Description: The changes in dependent and non-dependent silent spaces measured by EIT in PEEP 5 and 15.

Measure: Silent spaces

Time: Through study completion (up to 24 hours)

Description: Respiratory system compliance in PEEP 5 and 15.

Measure: Respiratory system compliance

Time: Through study completion (up to 24 hours)

Description: Oxygenation in PEEP 5 and 15.

Measure: Oxygenation

Time: Through study completion (up to 24 hours)

Description: Dead space ventilation ratio in PEEP 5 and 15.

Measure: Dead space ventilation ratio

Time: Through study completion (up to 24 hours)
274 COVID-19 Convalescent Plasma Treatment in SARS-CoV-2 Infected Patients: Multicenter Interventional Study

Due to the limitations of COVID-19 treatment and in the absence of licensed antiviral for COVID-19, the historical choice of therapeutic convalescent plasma (CP) is considered especially against RNA viruses .It was known that convalescent plasma does not only neutralize the pathogens but provide passive immunomodulatory properties that allows the recipient to control the exaggerated inflammatory cascade. However, still there is a lack of understanding of the mechanism of action of CCP therapeutic components. Reports from open label trials and case series show that CCP is safe and might be effective in severe cases with COVID-19 . Therefore, the World health organisation (WHO) and Food and Drug Administration (FDA) issued guidelines for the CCP usage and standardised the donor selection , which was further supported by Emergency use Authorisation (EUA) . Therefore, the aim in the current study is to assess the effect of CCP on time to clinical improvement, hospital mortality and to evaluate the changes on oxygen saturation and laboratory markers (lymphocyte counts and C-reactive protein) compared with standard treatment alone in patients with moderate or severe COVID-19 disease.

NCT04474340
Conditions
  1. Moderate COVID-19 Pneumonia, Severe COVID-19 Pneumonia
  2. Pneumonia, Viral
Interventions
  1. Drug: COVID-19 Convalscent Plasma
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time to clinical improvement is defined as a time frame from CCP administration till 30 days or discharge, defined as a 2-grade decrease on an ordinal WHO clinical scale . The WHO clinical scale based on the following 7-grade ordinal levels: 1= ambulatory, independent; 2= ambulatory with assistance; 3=hospitalised, not requiring supplemental oxygen; 4= hospitalised, requiring supplemental oxygen; 5= hospitalised, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6= hospitalised, requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both; and 7= death.

Measure: Time to clinical improvement

Time: 30 days

Secondary Outcomes

Measure: All cause mortality

Time: 30 days
275 Managed Access Program (MAP) to Provide Access to Canakinumab Treatment of Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia

This is a global Managed Access Program (MAP) to provide access to canakinumab to patients with cytokine release syndrome resulting from COVID-19 pneumonia

NCT04476706
Conditions
  1. Cytokine Release Syndrome in COVID-19-induced Pneumonia
Interventions
  1. Drug: canakinumab
MeSH:Pneumonia Syndrome
HPO:Pneumonia

276 A Safety Study on the Use of Intermittent Versus Continuous Inhalation of NO in Spontaneous Breathing COVID-19 Patients

Preliminary data support the effect of Nitric Oxide (NO) on improving the oxygenation in mechanically ventilated patients and spontaneously breathing patients with COVID-19. In vitro studies showed an antiviral effect of NO against SARS-coronavirus. The optimal therapeutic regimen of NO gas in spontaneously breathing hypoxemic patients with COVID-19 is not known. We hypothesize that high concentration inhaled NO with an adjunct of continuous low dose administration between the high concentration treatments can be safely administered in hypoxemic COVID-19 patients compared to the high dose treatment alone. Prolonged administration of NO gas may benefit the patients in terms of the severity of the clinical course and time to recovery. Together with a clinical effect on ventilation-perfusion matching, a prolonged regimen would allow also an increase in antiviral activity (dose and time-dependent).

NCT04476992
Conditions
  1. Hypoxemia
  2. Pneumonia, Viral
  3. Coronavirus Infection
Interventions
  1. Drug: Nitric Oxide-Sessions
  2. Drug: Nitric Oxide-Continuous and Sessions
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Hypoxia
HPO:Hypoxemia Pneumonia

Primary Outcomes

Description: The primary outcome will be evaluated with the difference in Methemoglobin levels between the groups at 48 hours after randomization.

Measure: Change in Methemoglobin level at 48 hours

Time: 48 hours

Secondary Outcomes

Description: The primary outcome will be evaluated with the difference in Methemoglobineamia between the groups at 96 hours after randomization.

Measure: Change in Methemoglobin level at 96 hours

Time: 96 hours

Description: The secondary outcome, "Improve the oxygenation at 48 hours," will be evaluated with the measure of the difference in oxygenation among the groups at 48 hours. Oxygenation will be measured in terms of the SpO2/FiO2 ratio.

Measure: Improvement in oxygenation between the groups at 48 hours or at discharge if before 48 hours

Time: 48 hours

Description: The secondary outcome, "Improve the oxygenation at 96 hours," will be evaluated with the measure of the difference in oxygenation between the groups at 96 hours. Oxygenation will be measured in terms of the SpO2/FiO2 ratio.

Measure: Improvement in oxygenation between the groups at 96 hours or at discharge if before 96 hours

Time: 96 hours

Description: The secondary outcome "difference in the rate of negative RT-PCR for SARS CoV-2" will be evaluated as the rate of negativization of the RT-PCR for SARS-CoV-2 at 5 days after randomization, at discharge and at 28 days after randomization.

Measure: Rate of positive RT-PCR for SARS-CoV-2 between groups in 5 days, discharge, and 28 days

Time: 28 days

Description: The secondary outcome "different time to clinical recovery" will be evaluated as the time between the randomization and the clinical indication to interrupt the administration of oxygen for 24 hours.

Measure: Time to clinical recovery among groups, defined as time to interruption of oxygen administration for 24 hours or discharge

Time: 28 days

Description: The secondary outcome "Different reduction in inflammatory markers" will be evaluated as improvement in the inflammatory markers (IL-6; Ferritin; White Blood Cells; Leucocyte count; CRP; D-Dimer) observed in blood samples collected at day 1, 2, 3, 4, and 7 compared to the Baseline value.

Measure: Reduction in the inflammatory markers among groups

Time: 7 days

Description: The secondary outcome "rate of AKI between groups" will be evaluated as the presence of a comparable rate of AKI during the hospital stay. The AKI will be defined according to the KDIGO classification.

Measure: Rate of Acute Kidney Disease (AKI) between groups during hospitalization

Time: 28 days

Description: The secondary outcome "Difference in Katz score between groups" will be evaluated as the difference in Katz Activities of Daily Living between Baseline and day 28. This questionnaire will coincide with the 28-day phone call to assess health status and survival.

Measure: Difference in Katz score between groups

Time: 28 days

Other Outcomes

Description: 1. The exploratory outcome "Effect of nitric oxide on heart function in COVID-19 hypoxemic patients" will be evaluated as: the changes observed in heart ultrasound at 48 and 96 hours (or at discharge) compared to the Baseline in all groups. the changes observed in heart ultrasound during the administration of NO comparing pre-treatment, during treatment, and post-treatment.

Measure: Effect of NO gas treatment on cardiovascular hemodynamics assessed using cardiac ultrasound in COVID-19 hypoxemic patients

Time: 96 hours

Description: 2. The secondary outcome "Effect of NO gas on lung function in COVID-19 hypoxemic patients" will be evaluated as: the changes observed in spirometry at 48 and 96 hours (or at discharge) compared to the Baseline in all groups. the changes observed in spirometry during the administration of NO comparing pre-treatment, during treatment, and post-treatment.

Measure: Effect of NO gas treatment on lung function evaluated with serial spirometry in COVID-19 hypoxemic patients

Time: 96 hours
277 Assessment of the Risk of Pulmonary Embolism and Coagulation Profile in Patients With SARS Coronavirus (COV-2) Lung Disease

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is complicated by pneumonia (15 to 20% of cases) requiring hospitalization with oxygen therapy. Almost 20 to 25% of hospitalized patients require intensive care and resuscitation; half die. The main cause of death is acute respiratory distress syndrome (ARDS). However, some deaths have been linked to pulmonary embolism (PE). Recognition of PE is important because there is specific treatment to limit its own mortality. The identification of biological parameters of hemostasis predictive of thromboembolic disease is crucial in these patients. To evaluate the frequency of PE in the patients having to be hospitalized is to practice of a systematic thoracic angiography scanner in the patients having no contra-indication for its realization, as well as during hospitalization in patients deteriorating without any other obvious cause. The thromboembolic events and disturbances of the coagulation system described in patients with SARS-CoV-2 pneumonitis suggest that this viral infection is associated with an increase in the activation of coagulation contributing to the occurrence of thrombosis and especially from PE.

NCT04479540
Conditions
  1. Pneumonia, Viral
Interventions
  1. Radiation: Angiography scanner
MeSH:Pneumonia, Viral Pneumonia Lung Diseases Pulmonary Embolism Embolism
HPO:Abnormal lung morphology Pneumonia Pulmonary embolism

Primary Outcomes

Description: Rate of patients with pulmonary embolism diagnosed by thoracic angiography scanner

Measure: Rate of patients with pulmonary embolism

Time: up to Day 12

Secondary Outcomes

Description: Measure of prothrombin level to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Prothrombin level measurement

Time: up to Day 12

Description: Measure of activated partial thromboplastin time to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: activated partial thromboplastin time measurement

Time: up to Day 12

Description: Measure of fibrinogen to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Fibrinogen measurement

Time: up to Day 12

Description: Measure of D-dimers to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: D-dimers measurement

Time: up to Day 12

Description: Measure of Protein C to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Protein C measurement

Time: up to Day 12

Description: Measure of Willebrand antigen to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Willebrand antigen measurement

Time: up to Day 12

Description: Measure of Soluble tissue factor to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Soluble tissue factor measurement

Time: up to Day 12

Description: Measure of soluble thrombomodulin to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Soluble thrombomodulin measurement

Time: up to Day 12

Description: Measure of E-selectin to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: E-selectin measurement

Time: up to Day 12

Description: Measure of thrombin-antithrombin complex to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

Measure: Thrombin-antithrombin complex measurement

Time: up to Day 12

Description: Assessment of clot formation curve by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis

Measure: Assessment of clot formation curve

Time: Day 1

Description: Assessment of thrombin generation by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis

Measure: Assessment of thrombin generation

Time: Day 1

Description: Assessment of fibrinolysis by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis

Measure: Assessment of fibrinolysis

Time: Day 1

Description: Determine patient mortality

Measure: Mortality

Time: Day 30
278 Laparoscopic Bariatric Surgery During Phase 2-3 Covid-19 Pandemic in Italy: a Multicenter, Prospective, Observational Study.

The first person-to-person Coronavirus disease (COVID-19) transmission in Italy was reported on Feb 21st, 2020, causing one of the most massive outbreak in Europe so far that stopped immediately all elective surgical procedures. Bariatric surgery represents the most effective treatment to obtain an important, long-term weight loss and comorbidities' resolution, including respiratory disorders. A sensitive decrease of epidemic has been observed lately and a gradual and progressive stop of the lockdown (phase 2-3) was planned, when the virus is supposed to be under control and protocols are guiding the restart of the elective bariatric surgery. Several questions are currently open: Laparoscopic bariatric surgery is safe in the phase 2-3? What's the expected complications rate? The actual hospital protocols are effective to minimize the risk of postoperative COVID-19 infection? Aim: to analyse results of bariatric surgery during phase 2-3 COVID-19 pandemic in Italy. Primary end point: 30 days COVID-19 infection, mortality and complications. Secondary end points: readmission rate 30 days, reoperations for any reason related to surgery. Study design: prospective multicenter observational. Setting: Italian National Health Service 8 high-volume bariatric centres. Enrollment criteria: No previous Covid-19 infection; Primary, standard IFSO approved bariatric procedures; No concomitant procedure; No previous major abdominal surgery; >18<60 years old; Compensated comorbidities; Official SICOB's surgical informed consent given, including COVID-19 addendum; Adherence to very restrictive protocols regarding: hospital admission, management of in-hospital patients and after discharge. Follow-up: scheduled outpatient visit 30th postoperative day. Data evaluation: all the cases performed during July/December 2020 will be collected in a prospective database. Patients operated during the period July/December 2019 in the same centers will be considered comparative group (control). Expected results: Transparent information to the patients, and the introduction of the COVID-19 protocol concerning patients and health-professionals protection, should guarantee a safe restart of bariatric surgery in Italy. The network of 8 high-volume centers sharing information and protocols in this "unexplored" period will be a guarantee for patients' safety. Bariatric surgery should induce a postoperative amelioration of the comorbidities reducing the risks in case of a second outbreak.

NCT04480034
Conditions
  1. Bariatric Surgery Candidate
  2. Covid19
  3. Complication of Surgical Procedure
  4. Pneumonia, Viral
  5. Viral Infection
  6. Obesity, Morbid
  7. Safety Issues
  8. Readmission
Interventions
  1. Procedure: Bariatric procedures
MeSH:Virus Diseases Pneumonia, Viral Pneumonia Obesity Obesity, Morbid
HPO:Obesity Pneumonia

Primary Outcomes

Description: Postbariatric surgery COVID-19 infection, mortality and complications

Measure: Postoperative COVID-19 infection

Time: 30 postoperative days

Secondary Outcomes

Description: Complications, reoperations for any reason related to bariatric surgery.

Measure: Complications related to bariatric surgery

Time: 30 postoperative days
279 A Randomized, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and in Combination With NA-831 in Healthy Volunteers

The clinical study is designed to evaluate the safety, tolerability and pharmacokinetics of inhaled nanoparticle nanoparticle formulation of Remdesivir (GS-5734) alone and in combination with NA-831 in 48 healthy volunteers.

NCT04480333
Conditions
  1. Covid19
  2. Corona Virus Infection
  3. Severe Acute Respiratory Syndrome
  4. Severe Acute Respiratory Infection
  5. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  6. Severe Acute Respiratory Syndrome of Upper Respiratory Tract
  7. Neurodegeneration
  8. Neuroinflammatory Response
Interventions
  1. Drug: Drug: NA-831 - 0.10 mg/kg
  2. Drug: Placebo- 0.10 mg/kg
  3. Drug: Drug: NA-831 - 0.20 mg/kg
  4. Drug: Placebo- 0.20 mg/kg
  5. Drug: Drug: GS-5734 - 1.00 mg/kg
  6. Drug: Placebo- 1.00 mg/kg
  7. Drug: Drug: GS-5734 - 2.00 mg/kg
  8. Drug: Placebo- 2.00 mg/kg
  9. Combination Product: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
  10. Combination Product: Placebo 0.10 mg + 1.00 mg/kg
  11. Combination Product: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)
  12. Combination Product: Placebo 0.20 mg + 2.00 mg/kg
MeSH:Infection Communicable Diseases Respiratory Tract Infections Virus Diseases Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Nerve Degeneration
HPO:Neurodegeneration Pneumonia Respiratory tract infection

Primary Outcomes

Description: AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0

Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events

Time: First dose date up to Day 30 Follow-up Assessment

Description: This will be assessed at various time points by clinical laboratory tests and vital signs.

Measure: Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities

Time: First dose date up to Day 30 Follow-up Assessment

Secondary Outcomes

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the maximum concentration (Cmax) of NA-831 and GS-5734 in human serum.

Measure: Maximum Concentration (Cmax) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the time to maximum concentration (Tmax) of NA-831 and GS-5734 in human serum

Measure: Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve from time of administration to the last measurable of NA-831 and GS-5734

Measure: AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve extrapolated to infinity (AUC0-∞) of NA-831 and GS-5734

Measure: Area Under the Curve Extrapolated to Infinity (AUC0-∞)

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the half-life (t1/2) of NA-831 and GS-5734 in human serum.

Measure: Half-Life (t1/2) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera through various time points to elucidate the volume of distribution (Vd) of NA-831 and GS-5734 in human serum.

Measure: Volume of Distribution (Vd) - Pharmacokinetic Assessment

Time: 7 days

Description: Monitoring of the levels of drugs in subject sera through at various time points to elucidate clearance [CL] of NA-831 and GS-5734 in human serum.

Measure: Clearance [CL] - Pharmacokinetic Assessment

Time: 7 days
280 Evaluation of Clinical Characteristics and Outcome of COVID19 Pneumonia in Assiut

- Evaluation of the clinical presentation of COVID 19 pneumonia. - Identification the risk factors of severing COVID 19 pneumonia. - Evaluation of the outcome of the disease.

NCT04481360
Conditions
  1. Coronavirus
Interventions
  1. Device: CT of the chest
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Patients assessment using CURB 65|(confusion ,urea level, respiratory rate blood pressure,age above 65 years) score 0 or 1 out patient -2 inpatient observation- 3 or more ICU admission.

Measure: Clinical evaluation

Time: through study completion, an average of 1 year
281 Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial

This is a a randomized double blind placebo controlled Phase 2 trial with a 12 patient lead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for a total of 40 patients) to assess efficacy of decitabine in the treatment of critically ill patients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receive standard of care plus Decitabine or standard of care plus saline based placebo. The primary objective is to determine safety and efficacy of decitabine for COVID-19 ARDS based on clinical improvement on a 6-point clinical scale.

NCT04482621
Conditions
  1. COVID-19
Interventions
  1. Drug: Decitabine
  2. Other: Placebo Saline
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical improvement within 10 days since start of treatment, defined as a decrease of at least 1 point within 10 days from baseline on a six-point ordinal scale: Not hospitalized/discharged; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane oxygenation (ECMO), or both; and Death.

Measure: Change in clinical state as assessed by a 6-point ordinal scale

Time: Baseline and daily up to day 10

Secondary Outcomes

Description: Safety assessments using adverse events will be monitored daily while inpatient and weekly through end of study at week 6 once discharged from hospital. They will be monitored and graded using Common Terminology Criteria Adverse Events version 5.0.

Measure: Safety as assessed by adverse events

Time: Up to 6 weeks

Description: Oxygenation index is used to assess severity of hypoxic respiratory failure. (OI = mean airway pressure (MAP) × Fraction of inspired oxygen (FiO2) × 100÷ partial pressure of oxygen (PaO2). This will be measured daily while subject is on mechanical ventilation up to 6 weeks.

Measure: Change in oxygenation index

Time: Daily, up to 6 weeks

Description: Fraction of inspired oxygen in the oxygen delivery system during hospital stay. Measured at 8 am daily during hospital stay and then weekly until day 29.

Measure: Change in fraction of inspired oxygen

Time: Up to day 29

Description: Number of days for subject that have a reduction by at least 2 point from baseline on a six point ordinal scale: Not hospitalized/discharged; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane oxygenation (ECMO), or both; and Death.

Measure: Time (days) to clinical improvement

Time: Up to 6 weeks

Description: Patients status of alive versus death at completion of study follow up period, i.e. 6 weeks from start.

Measure: Overall survival

Time: Up to 6 weeks

Description: Duration of days from baseline to hospital discharge.

Measure: Length of stay in hospital

Time: Till hospital discharge, up to 6 weeks

Description: For subjects who received mechanical ventilation, total number of days from baseline to end of study at 6 weeks that subject was not on mechanical or non invasive mechanical ventilation.

Measure: Ventilator free days

Time: Up to 6 weeks

Description: If viremic at starting date of decitabine - time from baseline to 1st recorded negative COVID nucleic acid amplification (NAT) based assay, measured in days.

Measure: Time to Polymerase chain reaction (PCR) negativity

Time: Up to 6 weeks

Description: Determines the degree of illness of a patient and prompts critical care intervention. This composite score includes Respiratory Rate, Temperature, oxygen Saturation, Blood Pressure, Oxygen inspired and cognitive status. This will be measured at baseline and weekly while patient is in hospital.

Measure: Percentage of patients with National Early Warning Score 2 of 3 or more

Time: Weekly while patient is in hospital, up to 6 weeks
282 Predicting the Progression to Chronic Fibrosis of Lung Lesions Related to Covid-19 Infection From Chest CT Images

The main differences observed between SARSCoV-2 pneumonia and other epidemic viral pneumopathies (e.g., seasonal influenza) are the greater infectivity of SARSCoV-2, the clinical severity of the disease, particularly in young patients without co-morbidities, and the observation of radiological images related to significant parenchymal aggression in a large number of patients. The lesions in the acute phase correspond essentially to bilateral ground glass opacity more or less associated with condensations which would be markers of more severe infections. The major scope of the lesions in the acute phase raises the question of whether or not the scanning anomalies are completely resolved over time, and the possible impact on lung function. This risk of sequelae is very important to study given the large number of patients affected by SARSCoV-2, especially since these are often young patients who appear to be "healthy". In the current context of the CoV-2 SARS pandemic, the improved quality and availability of diagnostic scanners provides a wealth of information on the semiology and progression of lung disease with minimal exposure to ionizing radiation. A majority of hospitalized patients with SARSCoV-2 received a CT scan in the early phase of the disease. Indeed, the French Society of Radiology has recommended the performance of a CT scan without injection in thin sections in case of suspicion or for confirmation of the diagnosis in patients presenting initial or secondary clinical signs of severity and justifying hospital management due to the initial lack of reagents for performing biological tests (RT-PCR) and the high sensitivity of the CT scan and its specificity in epidemic periods. The present study aims to study the kinetics of lung involvement in SARS CoV 2, to study the predictive character of the chest CT scan performed at the patient's discharge on the existence of radiological sequelae at 3 months but also at 1 year in order not to misunderstand the constitution of late fibrosis after partial resolution of the CT images. The investigatos will study the correlation between possible radiological abnormalities and the clinical presentation (patient symptoms and lung function). The rigorous follow-up of these patients will allow us to set up, if necessary, early treatment of the detected abnormalities (inhaled corticoids in case of bronchial or bronchiolar damage, study of the place of an anti-fibrosis treatment in case of fibrosis,...).

NCT04483752
Conditions
  1. CoV2 SARS Pneumonia
Interventions
  1. Other: CHEST CT SCAN
MeSH:Pneumonia Fibrosis
HPO:Pneumonia

Primary Outcomes

Measure: description of the different types of lesions

Time: 3 months

Secondary Outcomes

Measure: quantification of circulating antibodies and correlation between the level of immunization against SARS CoV2, the severity of the initial disease and the existence or not of long-term pulmonary sequelae

Time: 3 months
283 Place of Circulating Biomarkers and Respiratory Eicosanoids in the Prognosis of Severe Forms of Covid-19 Pneumonia: BioCovid Study

The research is a prospective, multicentric (Groupe hospitalier Paris Saint-Joseph, Centre Hospitalier de Versailles André Mignot and Centre Hospitalier Victor Dupouy), non-interventional, prospective study. It aims at measuring eicosanoids at different stages of Covid-19 infection.

NCT04485364
Conditions
  1. Coronavirus
  2. Covid19
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The importance of the inflammatory response in the evolution of respiratory disease during the the patients' hospital care based on criteria such as: The search for systemic biomarkers: the previous work led by the Saint Joseph Hospital Group team has highlighted the potential interest of biomarkers of inflammation in the diagnosis of infectious pathology as well as in the eventual prognosis of these patients. and the study of the production of eicosanoids and their presence in the systemic circulation and in the respiratory tree.

Measure: Inflammatory response in the evolution of respiratory diseases

Time: 6 months = the study duration

Secondary Outcomes

Description: Evolution of respiratory pathology during mechanical ventilation.

Measure: Impact of the respiratory disease during mechanical ventilation

Time: 6 months = the study duration
284 Efficacy Assessment of Methylprednisolone and Heparin in Patients With COVID-19 Pneumonia: A Randomized, Controlled, 2x2 Factorial Study

The COVID-19 pandemic has been spreading continuously, and in Brazil, until July 19, 2020, there have been more than 2,000,000 cases with more than 79,000 deaths, with daily increases. The present study proposes to evaluate the efficacy of methylprednisolone and heparin in treatment of patients with COVID-19 pneumonia in a randomized, controlled, 2x2 factorial study.

NCT04485429
Conditions
  1. COVID-19
Interventions
  1. Drug: Methylprednisolone
  2. Drug: Heparin
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Rate of invasive mechanical ventilation

Time: 28 days

Secondary Outcomes

Description: Severity assessment will be performed using the ordinal severity scale during hospitalization.

Measure: Severity assessment by ordinal severity scale

Time: 3 days, 7 days, 14 days, 28 days after randomization

Description: Severity assessment will be performed using the SOFA score during hospitalization.

Measure: Severity assessment by SOFA score

Time: 3 days, 7 days, 14 days, 28 days after randomization

Measure: Length of hospital stay

Time: 28 days

Measure: Length of stay in intensive care

Time: 28 days

Measure: Death rate

Time: 14 days, 28 days, 60 days, 90 days after randomization
285 Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection

In this study, a total of 80 patients with severe coronavirus disease 2019 (COVID-19) infection will be randomized to receive Duvelisib or a placebo. Participants will be enrolled at Emory University Hospital and at the University of Pennsylvania and will be identified and recruited by their treating physician and research team.

NCT04487886
Conditions
  1. COVID-19
Interventions
  1. Drug: Duvelisib
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.

Measure: Number of Participants Requiring Mechanical Ventilation or Dying

Time: Up to Day 29

Secondary Outcomes

Description: Time to recovery (in days) is defined as a score of greater than 5 from the following eight categories from the NIAID ordinal scale. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities.

Measure: Days to Recovery

Time: Up to Day 29

Description: The number of days spent hospitalized will be compared between study arms.

Measure: Duration of Hospitalization

Time: Up to Day 29

Description: The incidence of death within 29 days of randomization will be compared between study arms.

Measure: Incidence of Death

Time: Up to Day 29

Description: Comparing the proportion of subjects in each group requiring ICU transfer within 29 days of randomization

Measure: Proportion of Participants Transferred to ICU

Time: Up to Day 29

Description: The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active and 5 = dead. Median ECOG performance will be compared between study arms.

Measure: Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score

Time: Day 15, Day 29

Description: The incidence of grade III-V adverse events or Serious Adverse Events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, will be compared between study arms.

Measure: Incidence of Grade III-V Adverse Events

Time: Up to Day 29

Description: The incidence of documented secondary bacterial or viral infections among participants will be compared between study arms.

Measure: Incidence of Secondary Bacterial or Viral Infections

Time: Up to Day 29

Description: The mean frequency of Th1 T cells in blood mononuclear cells will be compared between study arms.

Measure: Change in Th1 T Cell Frequency

Time: Weeks 1, 2, and 4

Description: The mean frequency of Th17 T cells in blood mononuclear cells will be compared between study arms.

Measure: Change in Th17 T Cell Frequency

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IL-2 will be compared between study arms.

Measure: Change in Interleukin-2 (IL-2)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IL-2R will be compared between study arms.

Measure: Change in Interleukin-2 receptor (IL-2R)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IL-6 will be compared between study arms.

Measure: Change in Interleukin-6 (IL-6)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IL-7 will be compared between study arms.

Measure: Change in Interleukin-7 (IL-7)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IL-8 will be compared between study arms.

Measure: Change in Interleukin-8 (IL-8)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IL-10 will be compared between study arms.

Measure: Change in Interleukin-10 (IL-10)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker IP-10 will be compared between study arms.

Measure: Change in Interferon gamma-induced Protein 10 (IP-10)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker MIP-1a will be compared between study arms.

Measure: Change in Macrophage Inflammatory Protein 1alpha (MIP-1a)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker MCP-1 will be compared between study arms.

Measure: Change in Monocyte Chemoattractant Protein-1 (MCP-1)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker G-CSF will be compared between study arms.

Measure: Change in Granulocyte Colony-stimulating Factor (G-CSF)

Time: Weeks 1, 2, and 4

Description: Mean levels of the inflammatory serum biomarker TNF-alpha will be compared between study arms.

Measure: Change in Tumor Necrosis Factor (TNF)-alpha

Time: Weeks 1, 2, and 4

Description: VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.

Measure: Change in Vasoactive Intestinal Peptide (VIP)

Time: Weeks 1, 2, and 4

Description: Mean levels of the Tregs will be compared between study arms.

Measure: Change in Gene Expression Profile of Regulatory T Cells (Tregs)

Time: Weeks 1, 2, and 4

Description: Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.

Measure: Change in Gene Expression Profile of cluster of differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage colony-stimulating factor (GM-CSF)+

Time: Weeks 1, 2, and 4

Description: Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.

Measure: Change in Gene Expression Profile of CD8+ T cell immunoglobulin and mucin domain-containing protein 3 (Tim3)+ Programmed cell death protein 1 (PD-1)+

Time: Weeks 1, 2, and 4

Description: Mean levels of CD14+CD16+ monocytes will be compared between study arms.

Measure: Change in Gene Expression Profile of cluster of differentiation 14 (CD14)+ cluster of differentiation (CD16)+ monocytes

Time: Weeks 1, 2, and 4

Description: Mean levels of SARS-CoV-2 viremia in respiratory specimens will be compared between study arms.

Measure: Change in SARS-CoV-2 Viremia

Time: Weeks 1, 2, and 4

Description: Median titers of IgG antibodies to SARS-CoV-2 will be compared between study arms.

Measure: Change in Immunoglobulin G (IgG) Antibodies

Time: Weeks 1, 2, and 4

Description: Median titers of IgM antibodies to SARS-CoV-2 will be compared between study arms.

Measure: Change in Immunoglobulin M (IgM) Antibodies

Time: Weeks 1, 2, and 4

Description: Overall survival is defined as days from randomization to death and censored at last follow up.

Measure: Overall Survival

Time: Up to Day 29
286 N-terminal Pro B-type Natriuretic Peptide and Vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia

This study is designed to assess the difference between level of NT-pro-BNP, and Vitmin D in moderate cases who progressed to severe or critically ill category compared to those who did not. Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection.

NCT04487951
Conditions
  1. COVID19 Pneumonia
Interventions
  1. Other: Pro BNP , Vitamin D
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: level of NT-pro-BNP, and Vitamin D

Measure: NT-pro-BNP and Vitamin D

Time: 6 month

Secondary Outcomes

Description: Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection

Measure: Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection

Time: 6 month
287 Pathogens Involved in Secondary Infections During Severe Forms of Covid-19 Pneumonia: COVAP Study

A Respiratory infection with the SARS-CoV2 virus is associated with a major risk of viral pneumonia that can lead to respiratory distress requiring resuscitation. In the most severe forms, it may require mechanical ventilation or even lead to an acute respiratory distress syndrome with a particularly poor prognosis. The SARS-CoV2 is a single-stranded RNA virus of positive polarity and belongs to the beta genus of Coronaviruses. SARS-CoV2 is responsible for the third epidemic in less than twenty years secondary to a Coronavirus (SARS-CoV then MERS-CoV) and if the mortality associated with it is lower than that of previous strains, notably MERS-CoV, its spread is considerably big. As a result, the number of patients developing respiratory distress requiring invasive mechanical ventilation is high, with prolonged ventilation duration in these situations

NCT04488510
Conditions
  1. Covid19
  2. Ventilator Associated Pneumonia
  3. Nosocomial Pneumonia
MeSH:Pneumonia, Ventilator-Associated Healthcare-Associated Pneumonia Coinfection Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Establishing a biobank of the bacterial agents responsible for nosocomial pneumonia acquired under mechanical ventilation in order to: better understand the particularities of the bacteria responsible and obtain the "clinical" strains for in vitro studies that will be carried out secondarily.

Measure: Research of the bacteria responsible for nosocomial pneumonia

Time: 6 months

Secondary Outcomes

Description: Evaluation of the adhesion properties to the bronchial epithelium (LPS peculiarities of Gram-negative bacteria, the interaction with the virus in in vitro models and the different molecules of interest in the collected bronchial secretions).

Measure: Additional evaluations to the study

Time: 6 months
288 Phase I, Randomized, Double Blinded, Placebo Control Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Placebo to Treat Acute Pulmonary Inflammation Due to COVID-19 With Moderate to Severe Symptoms

The purpose of this study is to demonstrate the safety of Umbilical Cord Tissue Derived Mesenchymal Stem Cells (UCMSCs) administered intravenously in patients with acute pulmonary inflammation due to COVID-19 with moderately severe symptoms

NCT04490486
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Corona Virus Infection
Interventions
  1. Biological: UCMSCs
  2. Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Safety of UCMSCs will be reported as the percentage of participants in each treatment group that experienced a treatment related SAEs.

Measure: Percent of participants with treatment related Serious Adverse Events (SAE)

Time: 12 months

Secondary Outcomes

Description: Change in serum inflammatory marker levels including Interleukin (IL) IL-6, IL-2, Tumor Necrosis Factor Alpha (TNF-a) and procalcitonin will be evaluated in ng/L.

Measure: Change in inflammatory marker levels

Time: Baseline, Day 30

Description: Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.

Measure: Change in systemic inflammatory marker levels

Time: Baseline, Day 30

Description: Assessed using blood samples or nose/throat swabs.

Measure: COVID-19 Viral Load

Time: Up to 30 Days

Description: Sequential Organ Failure Assessment (SOFA) will be used to assess organ failure including the cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs. SOFA score ranges from 0-24 with the higher score indicating worse outcomes.

Measure: Change in SOFA score

Time: Baseline, Up to 30 Days

Description: Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.

Measure: Change in electrolytes levels

Time: Baseline, Up to 30 Days

Description: Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.

Measure: Change in LDH levels

Time: Baseline, Up to 30 Days

Description: ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.

Measure: Number of subjects discharged from the ICU

Time: Up to 7 Days

Description: Percentage of participants requiring less use of vasoactive agents will be reported.

Measure: Percentage of participants with less requirement for vasoactive agents

Time: Up to 30 Days

Description: Percentage of participant deaths throughout the study period.

Measure: Rate of Mortality

Time: Up to 30 Days

Description: The percentage of participants with changes in serum immune marker levels including Cluster of Differentiation (CD) CD 4+ and CD 8+, as evaluated by treating physician will be reported.

Measure: Percentage of participants with changes in immune marker expression

Time: Up to 30 Days

Description: Percentage of participants with changes in their chest imaging such as ground-glass opacity, local patch shadowing, bilateral patch shadowing and interstitial abnormalities will be reported. Imaging will be assessed by treating physician using chest radiography or chest Computed Tomography (CT).

Measure: Percentage of participants with changes in radiologic findings

Time: Up to 30 Days

Description: Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.

Measure: Percentage of participants with less pneumonia symptoms

Time: Up to 30 Days
289 The Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Two-Sided Pneumonia

Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection. According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes. This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.

NCT04491240
Conditions
  1. Covid19
  2. SARS-CoV-2 PNEUMONIA
  3. COVID-19
Interventions
  1. Drug: EXO 1 inhalation
  2. Drug: EXO 2 inhalation
  3. Drug: Placebo inhalation
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial

Measure: Number of Participants With Non-serious and Serious Adverse Events During Trial

Time: 30 days after clinic discharge

Description: Safety assessments such as adverse events during the inhalation procedures will be registered.

Measure: Number of Participants With Non-serious and Serious Adverse During Inhalation Procedure

Time: after each inhalation during 10 days

Secondary Outcomes

Description: Measure and compare time to clinical recovery compared to placebo. Time to clinical recovery calculated by the number of days the patient has hospitalized.

Measure: Time to Clinical Recovery (TTCR)

Time: from first inhalation until discharge from the clinic, up to 30 days

Description: The concentration of SpO2 by Pulse oximetry device during procedures in the groups. The measure was done before and after each inhalation (total 4 measures per day). The intraday SpO2 data of all patients in groups was calculated as Median with Inter-Quartile Range and presented in the table by days.

Measure: SpO2 Concentration

Time: 10 days during inhalation

Description: Blood biochemistry C reactive protein level in serum.

Measure: C-reactive Protein

Time: At the begining of inhalation (day 1) and on next day of last inhalation (day 11)

Description: Lactic Acid Dehydrogenase (LDH) level in serum

Measure: Lactic Acid Dehydrogenase (LDH)

Time: At the beginning of inhalation (day 1) and on next day of last inhalation (day 11)
290 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation

The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

NCT04492514
Conditions
  1. COVID 19
  2. SARS-CoV 2
  3. Pneumonia
Interventions
  1. Drug: Mavrilimumab
  2. Drug: Placebo
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: Proportion of subjects alive and off oxygen at day14

Measure: Primary Outcome Measure:

Time: Day 14

Secondary Outcomes

Description: Proportion of subjects alive and without respiratory failure at 28 days

Measure: Secondary Outcome Measures:

Time: 28 days
291 Extracellular Vesicle Infusion Treatment for Severe COVID-19

To evaluate the safety and efficacy of intravenous administration of bone marrow derived extracellular vesicles, ExoFlo, versus placebo as treatment for moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) in patients with severe COVID-19.

NCT04493242
Conditions
  1. Covid19
  2. ARDS
  3. Pneumonia, Viral
Interventions
  1. Biological: DB-001
MeSH:Pneumonia, Viral Pneumonia Blister
HPO:Pneumonia

Primary Outcomes

Description: all-cause mortality

Measure: all-cause mortality

Time: 28 days

Description: median days to recovery

Measure: median days to recovery

Time: 28 days
292 Low Dose Whole Lung Radiotherapy for Older Patients With Coronavirus 19 Disease (COVID-19) Pneumonitis: Practical Protocol by the International Geriatric Radiotherapy Group

Low dose whole lung radiotherapy may improve survival of older patients with COVID-19 pneumonitis

NCT04493294
Conditions
  1. COVID-19 Pneumonitis
Interventions
  1. Radiation: Low dose whole lung radiotherapy for older patients with COVID-19 pneumonitis
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Comparing mortality rate of the whole group of patients treated with low dose whole lung radiotherapy with historical data

Measure: Mortality rate

Time: One year

Secondary Outcomes

Description: Comparison mortality rate of different ethnic groups treated with whole lung radiotherapy for COVID-19 pneumonia

Measure: Mortality rate

Time: One year

Description: Duration of hospitalization for the whole group and different groups with or without oxygen requirement

Measure: Duration of hospitalization

Time: One year

Description: Ordinal scale at the time of radiotherapy and 28 days later

Measure: Time to recovery

Time: One month

Description: Correlation between oxygen saturation rate and ordinal scale at different times following radiotherapy

Measure: Oxygen saturation rate

Time: One year

Description: Biomarkers for inflammation such as Interleukin 6 will be monitored and correlated with ordinal scale at different times following radiotherapy

Measure: Patient inflammatory status

Time: One year
293 An Open-label Multicenter Randomized Trial to Evaluate the Efficacy of Bioven, Manufactured by Biopharma Plasma, LLC, in Complex Therapy of Patients With Pneumonia Induced by COVID-19 / SARS-CoV-2

Pneumonia caused by coronavirus infection COVID-19 is characterized by a combination of several dangerous factors that consistently worsen the patient's condition: viral lung damage early in the disease; a sharp increase in inflammation on the background of an unbalanced immune response ("cytokine storm"); joining a bacterial infection. The condition of patients deteriorates significantly mostly at cytokine storm development. The damaging of a large volume of lung tissue leads to develops of respiratory failure, respiratory distress syndrome, or shock. Ventilatory support becomes ineffective and patients die. There are reports of the effectiveness of Human Normal Immunoglobulin for Intravenous Administration (IVIG) high doses when used as part of complex therapy in patients with pneumonia caused by coronavirus COVID-19. In particular, IVIG has a positive effect on survival rates, overall disease course, duration of stay in the intensive care unit, and ventilatory support duration. The probable mechanism of action of high-dose IVIG therapy is considered to be a regulatory effect on the immune system. Similar is the known and confirmed effectiveness of IVIG for autoimmune diseases (Kavasaky disease, Guillain Barre syndrome, Chronic inflammatory demyelinating polyradiculoneuropathy, Multifocal motor neuropathy). This trial to assesses the Efficacy of IVIG (medication trade name - Bioven, manufactured by Biopharma Plasma LLC) in the High Immunomodulatory Dose in Complex Treatment of Severe Pneumonia Caused by COVID-19 / SARS-CoV-2

NCT04500067
Conditions
  1. Covid19
  2. Pneumonia
Interventions
  1. Drug: IVIG
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of days post-onset of severe pneumonia to the moment of normalization at least two from following primary outcomes: O2 saturation with self-breathing, respiratory movements rate with self-breathing, body temperature without antipyretics use, lymphocyte count (targeted levels set in the description each of these primary outcomes)

Measure: Period duration (in days) to clinical improvement

Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

Description: The target level of SPO2 percentage - 95% and above with self-breathing, is used as one of the clinical improvement criteria

Measure: O2 saturation (SPO2 percentage), with self-breathing

Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

Description: The target level of respiratory movements - 28 per minute or less with self-breathing, is used as one of the clinical improvement criteria

Measure: Respiratory movements rate (amount per minute), with self-breathing

Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

Description: Measured in degrees Celsius. Fever absence (body temperature no more 37 degrees Celsius) during at least 24 hours without antipyretics, is used as one of the clinical improvement criteria.

Measure: Body temperature without antipyretics use

Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

Description: The target level 1000 cells / mm3 and above is used as one of the clinical improvement criteria (applicable for patients with lymphocytes count lower 1000 cells / mm3 at screening moment)

Measure: Lymphocyte count

Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

Secondary Outcomes

Description: Period duration (in days)

Measure: Time from the onset of the disease to discharge, in days

Time: 28 days

Description: Number of days with ventilatory support

Measure: Duration of the need for ventilatory support, in days

Time: 28 days

Description: Number of days in the intensive care unit

Measure: Duration of the need for intensive care, in days

Time: 28 days

Description: Number of days with necessery of oxygenation support

Measure: Duration of need for oxygenation in days (SPO2 ≤ 93% with self-breathing)

Time: 28 days

Description: Measuring the analyte concentration in plasma (mg/L)

Measure: The C-reactive protein (CRP) level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Measuring the analyte concentration in plasma (pg/mL)

Measure: The tumor necrozis factor alpha (TNF-α) level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Measuring the analyte concentration in plasma (pg/mL)

Measure: The interleukin-1β (IL-1β) level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Measuring the analyte concentration in plasma (pg/mL)

Measure: The interleukin-6 (IL-6) level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Measuring the analyte concentration in plasma (µg FEU/mL)

Measure: The D-dimer level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Measuring the analyte concentration in plasma (g/L)

Measure: The Complement (C3 component) level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Measuring the analyte concentration in plasma (U/mL)

Measure: The Circulating immune complexes level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Analyte concentration in plasma (ng/mL)

Measure: The ferritin level

Time: Day 0 (screening), day 5, day 14, day 28

Description: Analyte concentration in plasma (ng/mL)

Measure: The procalcitonin level

Time: Day 0 (screening), day 5, day 14, day 28

Description: The IgG-subtypes (IgG1-IgG4) concentration in plasma (mg/dL)

Measure: IgG subtypes

Time: Day 0 (screening), day 5, day 14, day 28

Description: Survivealance estimation

Measure: Survival assessment for a 28-day follow-up period since the onset of severe pneumonia

Time: 28 days

Other Outcomes

Description: Number of participants with adverse reactions related by investigational drug as assessed by CTCАЕ v 4.0

Measure: Frequency of side effects

Time: 28 days

Description: Number of participants with serious adverse reactions related by investigational drug as assessed by CTCАЕ v 4.0

Measure: Frequency of serious side effects

Time: 28 days
294 Phase 2, Multi-center, Randomized, Double-blind, Placebo- Controlled Study to Evaluate the Safety and Efficacy of EC-18 in COVID-19 Infection to Pneumonia

Prevention of COVID-19 infection to severe pneumonea or ARDS

NCT04500132
Conditions
  1. COVID-19
Interventions
  1. Drug: EC-18
  2. Drug: Placebo EC-18
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Rate of transition to ARDS

Time: 14 days after starting IP administration
295 One-year Cardiac Follow-up of Patients With COVID-19 Pneumonia

The primary objective of the study is to assess the cardiac status of COVID-19 pneumonia patients during 1 year after discharge

NCT04501822
Conditions
  1. Covid19
  2. Cardiac Complication
Interventions
  1. Diagnostic Test: Evaluation of clinical, instrumental and laboratory diagnostics tests
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Echocardiographic assessment of global strain parameters at 3 and 12 months after discharge

Measure: Echocardiographic assessment of cardiac function

Time: up to one year

Secondary Outcomes

Description: Major adverse cardiac and cerebrovascular events: cardiac death, myocardial infarction, or stroke at 3 and 12 months after discharge

Measure: МАССЕ

Time: up to one year

Description: Describe the parenchymal lung damage through a quantitative analysis with chest CT at 3 and 12 months after discharge

Measure: Quantitative analysis of parenchymal lung damage

Time: up to one year

Description: Six-min walk test at 3 and 12 months after discharge

Measure: Functional exercises capacity assessment

Time: up to one year

Description: Measure of creatinine clearance at 3 and 12 months after discharge

Measure: Evaluation of renal function

Time: up to one year

Description: Analysis for C-reactive protein at 3 and 12 months after discharge

Measure: Evaluation of inflammation

Time: up to one year

Description: Analysis for activated clotting time at 3 and 12 months

Measure: Evaluation of coagulation abnormality

Time: up to one year

Description: Assessment of the Short Form Health Survey (SF36) at 3 and 12 months after discharge

Measure: Evaluation of quality of life in first year after discharge

Time: up to one year
296 Treatment of COVID-19 With Opaganib in Patients With Pneumonia Requiring Oxygen But Not Mechanical Ventilation

Patients diagnosed with COVID-19 infection will be offered treatment with Opaganib, 500 mg Q12 hours. Opaganib will be continuously administered for up to 2 weeks, until discharged on room air (if earlier than 2 weeks).

NCT04502069
Conditions
  1. COVID-19
  2. Lung Infection
Interventions
  1. Drug: Opaganib
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To determine the time to breathing room air (off of supplemental oxygen) after the start of opaganib treatment.

Measure: Time to breathing room air

Time: Up to 2 weeks

Description: All adverse events will be graded according to the revised NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0). If an AE is not listed in the NCI-CTCAE v.5.0, then the Investigator will use the terms: mild, moderate, severe, life-threatening, or death to describe the maximum intensity of the AE.

Measure: Adverse Event Grading and Coding

Time: Up to 2 weeks
297 Study of a Possible Respiratory Degradation Prognosis Caused by Biomarkers in Severe Forms of COVID-19 Pneumonia: the LPSARS2 Study

Respiratory infection with the SARS-CoV2 virus is associated with a major risk of viral pneumonia that can lead to respiratory distress requiring resuscitation. In the most severe forms, it may require a mechanical ventilation or even lead to an acute respiratory distress syndrome with a particularly poor prognosis. The SARS-CoV2 is a single-stranded RNA virus of positive polarity and belongs to the beta genus of Coronaviruses. SARS-CoV2 is responsible for the third epidemic in less than twenty years secondary to a Coronavirus (SARS-CoV then MERS-CoV) and if the mortality associated with it is lower than that of previous strains, particularly MERS-CoV (Middle East Respiratory Syndrome), its spread is considerably bigger. As a result, the number of patients developing respiratory distress that require an invasive mechanical ventilation is high, with prolonged ventilation duration in these situations.

NCT04505605
Conditions
  1. Community-acquired Pneumonia
  2. Covid19
Interventions
  1. Other: Blood samples
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The study aims at evaluating the interests of the biomarkers dosage: endotoxin (LPS) and circulating cytokines (HMGB1 or RAGE) in the prediction of respiratory degradation through a severe form of COVID-19 acquired pneumonia that requires a hospitalization.

Measure: Evaluation of the dosage of biomarkers

Time: 6 months = study duration

Secondary Outcomes

Description: The study will be also focusing on the search for a correlation between the biomarkers by blood samples that will be taken on each hospitalized patients.

Measure: Link between the biomarkers

Time: 6 months = study duration
298 Clinical, Laboratory and Imaging Comparison Between COVID-19 Pneumonia Confirmed by PCR Detection on Nasopharyngeal Swab and Negative Swab Pneumonia

In the late 2019 a new Coronavirus was identified as the cause of a group of atypical interstitial pneumonia cases in Wuhan, a city in the Chinese province of Hubei. In February 2020, the World Health Organization designated COVID-19 disease, which stands for Coronavirus 2019 disease. Following the progressive spread of the infection in other countries of the world, WHO declared the Pandemic on 11 March 2020. Italy was the first European country involved in the spread of the infection and among those with the highest number of victims. The Coronavirus responsible for COVID-19 has, as its main target organ, the respiratory system, being able to determine a serious acute respiratory syndrome similar to that of the cases found during the SARS epidemic of 2003: hence the name of the virus as SARS-CoV-2. The diagnosis of SARS-COV-2 infection is made by direct detection by PCR of viral RNA on different biological materials from patients with suspicious symptoms, and the first level diagnostic test is generally the nasopharyngeal swab. However, even if the specificity of the nasopharyngeal swab is high, its sensitivity can be affected by technical causes (sampling mode), as well as by intrinsic factors related to the method. The purpose of the study is to identify the clinical, laboratory and imaging characteristic which are similar or which can differentiate the hospitalized patients affected by COVID-19 pneumonia (with positive PCR on naso-pharyngeal swab) and patients with pneumonia with negative PCR for COVID-19. To do this, the investigators will compare the clinical, laboratory and imaging characteristics between interstitial pneumonia secondary to SARS-COV-2 infection, confirmed by molecular biology investigations (viral RNA research by PCR on nasopharyngeal swab) and cases of interstitial pneumonia negative to the nasopharyngeal swab.

NCT04507893
Conditions
  1. Covid19
  2. Interstitial Pneumonia
Interventions
  1. Other: Clinical, laboratory and imaging characteristics of pneumonia
MeSH:Pneumonia Lung Diseases, Interstitial
HPO:Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pneumonia

Primary Outcomes

Description: Accuracy of severity of respiratory insufficiency - evaluated as need of three step "nasal oxygen, oxygen mask, invasive ventilation" - in differentiate COVID-19 infection, classified according to the results of PCR assay for COVID-19 on naso-pharyngeal swab as "COVID-19 patients" and "COVID-19 negative controls"

Measure: Evaluation of the clinical characteristics of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

Time: 75 Days

Description: Accuracy of the association of 3 haemato-chemical abnormalities (lymphopenia + increased serum transaminases + increased serum LDH) in differentiate COVID-19 infection, classified according to the results of PCR assay for COVID-19 on naso-pharyngeal swab as "COVID-19 patients" and "COVID-19 negative controls".

Measure: Evaluation of the laboratory characteristics of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

Time: 75 Days

Description: Accuracy of thorax CT scan in differentiate COVID-19 infection, classified according to the results of PCR assay for COVID-19 on naso-pharyngeal swab as "COVID-19 patients" and "COVID-19 negative controls".

Measure: Evaluation of the imaging characteristics of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

Time: 75 Days

Secondary Outcomes

Description: Evaluation of mortality in "COVID-19 patients" and "COVID-19 negative controls", hospitalized in the study period.

Measure: Evaluation of mortality of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

Time: 75 Days

Description: Evaluation of clinical severity in "COVID-19 patients" and "COVID-19 negative controls", hospitalized in the study period.

Measure: Evaluation of clinical severity of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

Time: 75 Days

Description: Evaluation of hospital stay length in "COVID-19 patients" and "COVID-19 negative controls", hospitalized in the study period.

Measure: Evaluation of hospital stay length of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

Time: 75 Days
299 Effect of the Use of Anticoagulant Therapy During Hospitalization and Discharge in Patients With COVID-19 Infection

Viral infections provoke the systemic inflammatory response and cause an imbalance between the procoagulant and anticoagulant homeostatic mechanisms. Multiple pathogenic mechanisms are involved, including endothelial dysfunction, increased von Willebrand factor, Toll receptor activation, and tissue factor pathway activation. D-dimer levels greater than 1000 ng / mL are associated with an 18-fold increased risk of mortality. In this context, many patients may require prophylaxis or antithrombotic treatment with low molecular weight heparins. Currently, there is no validated scheme on the dose and timing of the use of antithrombotic drugs. The study aims to identify the effect of two anticoagulant strategies (prophylactic and therapeutic) on the progression to ventilatory support or death in patients with COVID-19 infection who require hospital care.

NCT04508439
Conditions
  1. Covid19
  2. Pneumonia
  3. Coagulation Disorder
  4. Pulmonary Embolism
Interventions
  1. Drug: Enoxaparin
MeSH:Pneumonia Pulmonary Embolism Embolism Hemostatic Disorders Blood Coagulation Disorders
HPO:Abnormality of coagulation Abnormality of the coagulation cascade Pneumonia Pulmonary embolism

Primary Outcomes

Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) on ventilatory support time in patients requiring hospital care for COVID-19 infection.

Measure: low molecular weight heparin (enoxaparin) and ventilatory support time

Time: 30 days

Description: To compare oral anticoagulation therapy by administering Rivaroxaban 10mg PO every 24 hours on early thrombotic complications

Measure: thrombotic complications and Rivaroxaban

Time: 30 days

Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) on the length of hospital stay in patients requiring hospital care for COVID-19 infection.

Measure: low molecular weight heparin (enoxaparin) and length of hospital stay

Time: 30 days

Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) over mortality rate in patients requiring hospital care for COVID-19 infection.

Measure: low molecular weight heparin (enoxaparin) and mortality rate

Time: 30 days
300 A Practical, Pilot, Randomized, Controlled Trial of Valproate Alone or in Combination With Quetiapine for Severe COVID-19 Pneumonia With Agitated Delirium

The primary purpose of this research is to determine whether Valproate alone, and in combination with Quetiapine, lowers confusion and agitation in persons with severe Corona Virus Disease (COVID)19 pneumonia during weaning from the breathing machine (ventilator). Though Valproate and Quetiapine are often given to persons with severe confusion with agitation, the purpose of this small research study is specifically for: a) persons infected with COVID 2019 on a ventilator whose agitation is not responding to the usual medications (like dexmedetomidine), and b) to reduce the time persons are treated with dexmedetomidine, which requires continuous close monitoring in an ICU.

NCT04513314
Conditions
  1. Covid19
  2. Hyperactive Delirium
  3. Pneumonia, Viral
Interventions
  1. Drug: Valproate
  2. Drug: Quetiapine
  3. Other: Standard of Care
MeSH:Pneumonia, Viral Pneumonia Delirium
HPO:Pneumonia

Primary Outcomes

Description: Richmond Agitation Sedation Scale (RASS) score ranges from +4 (combative) to 0 (alert & calm) to -5 (unarousable).

Measure: Change from baseline RASS score of +3 or greater

Time: Baseline, Day 7

Secondary Outcomes

Description: Total dose of dexmedetomidine administered will be reported from baseline RASS score of +3 or greater.

Measure: Total dose of dexmedetomidine administered

Time: Day 7

Description: Incidence of Treatment Emergent Adverse Events will include: QTc duration > 470 msecs. Increase in Liver Function Tests to a Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Suicidality reported as having a score of moderate or high risk using the Columbia-Suicide Severity Rating Scale Screening (C-SSRS). C-SSRS is a calculated risk assessment tool that scores suicidality from no risk to high risk.

Measure: Incidence of Treatment Emergent Adverse Events

Time: Day 7
301 Prone Position and Respiratory Outcomes in Non-Intubated COVID-19 PatiEnts The "PRONE" Study

The overall objective of this study is to determine whether a positional maneuver (e.g., prone positioning) decreases the need for escalation of respiratory-related care in patients with coronavirus (COVID-19) pneumonia.

NCT04517123
Conditions
  1. Covid19
  2. Pneumonia, Viral
Interventions
  1. Other: Prone Positioning
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Participants will be assessed for the occurrence of an escalation in respiratory related care (Yes or No). Escalation in respiratory related care is clinically defined as any of the following: intubation any increase in flow of supplemental oxygen transition to high flow nasal cannula increase in fraction of inspired oxygen transfer from a lower to a higher level acuity of care (e.g. medical floor to intermediate care unit (IMC) or intensive care unit (ICU); IMC to ICU).

Measure: Occurrence of an escalation in respiratory related care (yes vs no)

Time: During hospitalization, up to 30 days

Secondary Outcomes

Description: Oxygen Saturation measured in percent oxygen over a 24-hour period.

Measure: Oxygen Saturation

Time: Over a consecutive 24-hour period after randomization

Description: Respiratory effort will be assessed using the respiratory rate (in breaths per minute) over a 24-hour period.

Measure: Respiratory Effort as assessed by Respiratory Rate

Time: Over a consecutive 24-hour period after randomization
302 Toclizumam Versus Dexamethasone in Severe Covid-19 Cases

randomized controlled trial comparing survival benefit of Tocilizumab therapy with dexamethasone in patients with severe COVID 19

NCT04519385
Conditions
  1. Pneumonia, Viral
Interventions
  1. Drug: Tocilizumab
  2. Drug: Dexamethasone
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: survival 14 days from admission date

Measure: Proportion of participants with Overall Survival at 14 days

Time: 14 days

Secondary Outcomes

Description: Change in Fio2/Pao2

Measure: Fio2/Pao2

Time: 2 days
303 Prospective Hospital Registry of Patients With Suspected or Confirmed Coronavirus Infection (COVID-19) and Community-acquired Pneumonia

Coronavirus-2019 disease (COVID-19) and community-acquired pneumonia are significant problems of modern medicine. Pneumonia is the most common severe complication of COVID-19. But at the same time, COVID-19 is not the only cause of community-acquired pneumonia. Moreover, pneumonia is only one of the numerous possible severe complications of COVID-19. Medical centers specialized for the hospital treatment of patients with severe COVID-19 and community-acquired pneumonia were organized in different regions of Russia during coronavirus pandemic-2020. The indications for hospitalization to one of these centers based in the National Medical and Surgical Center (NMSC) are: confirmed or suspected severe COVID-19 or community-acquired pneumonia. A prospective medical registry of such patients hospitalized to NMSC, is intended to analyze and compare their clinical and instrumental data, co-morbidity, treatment, short-term and long-term outcomes in real clinical practice. Stage 1. Hospital treatment in NMSC Duration of this stage: from the date of admission to the hospital up to the date of discharge from the hospital / or up to the date of death during the reference hospitalization. The date of admission to the hospital will be the date of enrollment to the study. Evaluation of electronic health record data using the Medical Information System (MIS). Assessment of the outcomes of the hospital phase (discharge from the hospital, death) and significant events (acute respiratory and pulmonary failure, requiring mechanical ventilation; cardiovascular events - myocardial infarction, cerebral stroke, acute heart failure, paroxysmal heart rhythm disturbances, bleedings, thrombosis of large vessels and thromboembolic complications). A survey of patients to clarify data on risk factors, somatic diseases, and drug therapy before hospitalization. COVID-19 was diagnosed when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed by Polymerase chain reaction (PCR). Pneumonia was confirmed according to computerized tomography (CT) data. Stage 2. Prospective outpatient follow-up for 24 months Duration of this stage: 24 months after discharge from the hospital This work will be delivered by investigators from the National Medical Research Center for Therapy and Preventive Medicine. Evaluation of long-term outcomes and events among residents of Moscow and the Moscow Region according to a patient survey (contact by phone for 30-60 days, 6 months, 12 and 24 months after discharge from the hospital) and medical records.

NCT04522076
Conditions
  1. COVID 19
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Overall survival

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Time to all-cause mortality or Artificial Pulmonary Ventilation (APV)

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Time to all-cause mortality, nonfatal myocardial infarction, nonfatal cerebral stroke, and coronary or carotid revascularization

Time: from discharge up to two years after reference hospitalization

Secondary Outcomes

Description: Damage area >50% according to the computer tomography data at any time point during hospitalization

Measure: Proportion of patients with severe pneumonia

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Description: SpO2 <90% - at any point during hospitalization

Measure: Proportion of patients with low oxygen saturation value

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Proportion of patients with Hb <90 g/l (9.0 g/dl) at any point during hospitalization

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Proportion of patients hospitalized or transferred to Intensive Care Unit (ICU)

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Overall survival

Time: from discharge up to two years after reference hospitalization

Measure: Time to nonfatal myocardial infarction, nonfatal cerebral stroke, and coronary or carotid revascularization

Time: from discharge up to two years after reference hospitalization

Description: In patients with pneumonia during reference hospitalization time to recurrent pneumonia. In patients without pneumonia during reference hospitalization - time to first pneumonia

Measure: Time to pneumonia/recurrent pneumonia

Time: from discharge up to two years after reference hospitalization

Description: In patients without COVID-19 - time to primary diagnosis and in patients with COVID-19 - time to recurrent event

Measure: Time to primary or recurrent coronavirus infection disease (COVID-19)

Time: from discharge up to two years after reference hospitalization

Other Outcomes

Measure: proportion of patients with nonfatal myocardial infarction

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: proportion of patients with nonfatal cerebral stroke

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: proportion of patients with bleedings

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Description: proportion of patients with thromboembolic events

Measure: thromboembolic events

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Description: the sum of the days when the patients required artificial pulmonary ventilation

Measure: Duration of Artificial Pulmonary Ventilation

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Minimal value of oxygen blood saturation (SpO2) during the hospital stage.

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Measure: Minimal value of hemoglobin (Hb) during the hospital stage

Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

Description: proportion of patients with rehospitalization due to pneumonia, COVID-19, flu and other acute respiratory infections (ARV)

Measure: Rehospitalization due to pneumonia, COVID-19, flu and other acute respiratory infections (ARV)

Time: from discharge up to two years after reference hospitalization

Description: proportion of patients with hospitalization due to cardiovascular disease

Measure: Hospitalization due to cardiovascular disease (CVD)

Time: from discharge up to two years after reference hospitalization

Measure: time to Flu and other ARV (except COVID-19)

Time: from discharge up to two years after reference hospitalization
304 An Exploratory Study of ADR-001 in Patients With Severe Pneumonia Caused by SARS-CoV-2 Infection

Safety and efficacy of ADR-001 are evaluated in Patients with Severe Pneumonia caused by SARS-CoV-2 infection.

NCT04522986
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
Interventions
  1. Biological: Mesenchymal stem cell
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Adverse events which appear in subjects with ADR-001 treatment are evaluated.

Measure: Safety: Adverse Event

Time: 12 weeks
305 Low-Level Laser Therapy Treatment of Lung Inflammation in COVID-19 Patients

To determine if a reduction of pneumonic inflammation occurs after treatment with Low-Level Laser Therapy (LLLT) applying red-light technology in the respiratory system of COVID-19 patients suffering from acute viral pneumonia.

NCT04524715
Conditions
  1. Covid19
Interventions
  1. Device: Non-invasive red LLLT treatment to chest of patient.
  2. Device: Sham Device Treatment
MeSH:Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Change in inflammation of the lungs as measured by O2 saturation levels

Measure: Inflammation of the lungs - O2

Time: 10 days

Description: Change in inflammation of the lungs as measured by C-Reactive Protein (CRP) Test

Measure: Inflammation of the lungs - CRP

Time: 10 days

Description: Change in inflammation of the lungs as measured by IL-6 Levels

Measure: Inflammation of the lungs - IL6

Time: 10 days
306 A Phase I/Ⅱa Trial to Explore the Safety and Efficacy of Allogenic Adipose Tissue-derived Mesenchymal Stem Cell (AstroStem-V) Therapy in Patients With COVID-19 Pneumonia

This study is an open-label, single-arm study to evaluate the safety and efficacy of Astrostem-V, allogenic adipose tissue derived mesenchymal stem cells (AdMSC), in patients with COVID-19 pneumonia. After each subject completes 12-Weeks visit (Visit 12) and the data management team confirms all individual data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.

NCT04527224
Conditions
  1. Covid19
Interventions
  1. Drug: AstroStem-V
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms.

Measure: Treatment related adverse events

Time: From baseline to Week 12

Description: Number of subjects with treatment related adverse events as assessed by analysis of adverse events including abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination.

Measure: Number of subjects with treatment related abnormal variation of vital signs, physical examination and laboratory test values

Time: From baseline to Week 12

Secondary Outcomes

Description: Change from baseline in Oxygenation index (PaO2 / FiO2 ratio) at every week

Measure: Oxygenation index (PaO2 / FiO2 ratio)

Time: From baseline to Week 12

Description: Check survival status of the subject at Visit 6, 10(Week 4, 8 and Week 12 if follow-up is possible) and record the status on eCRF.

Measure: Mortality rate

Time: Week 4, Week 8, and Week 12

Description: Check the duration of the ventilator retention, check when the ventilator treatment has been completed after the baseline.

Measure: Ventilator treatment status

Time: From Week 1 to Week 12

Description: Perform chest X-ray or CT every week (W1 - W4) after screening, baseline, and W4 followed by 2 - week intervals (W6, W8). The investigator of each clinical trial organ shall check chest X-ray or CT for bilateral shading and evaluate them.

Measure: Improvement of pneumonia

Time: From baseline to Week 12

Description: Check the SOFA score every week from the baseline to the W4 (W1 - W4) and 2 weeks after the W4 (W6, W8). The Sequential Organ Failure Assessment (SOFA) is a simple and clinically useful indicator that can be used to assess, predict, and monitor long-term failure in patients with multiple organ failure, and therefore increase in SOFA score can be expected to result in multiple organ failure and worse prognosis.

Measure: SOFA score (Sequential Organ Failure Assessment)

Time: From baseline to Week 12

Description: The Real-time PCR (RT-PCR) test for COVID-19 is measured at weekly intervals (W1 - W4) from baseline to baseline to W4 and 2 weeks after W4.

Measure: 2019 nCOV nucleic acid test

Time: From baseline to Week 12

Description: Check hospitalization date, date of admission at intensive care unit, or discharge date and record them in eCRF.

Measure: Duration of total hospitalization and intensive care unit stay (days)

Time: From baseline to Week 12
307 Multicenter, Randomized, Double-blind, Placebo-controlled Pilot Study of Treamid Efficacy and Safety in the Rehabilitation of Patients After COVID-19 Pneumonia

The innovative drug Treamid is planned for use in the rehabilitation of patients after COVID-19 pneumonia in a pilot, multicenter, randomized, double-blind, placebo-controlled Phase II clinical study to assess the efficacy and safety of Treamid, tablets, 50 mg in patients with fibrotic changes in the lungs after COVID-19 pneumonia during a 28-day treatment. The primary objective of the study is to demonstrate the efficacy of Treamid tablet, 50 mg in change in forced vital capacity (FVC) and/or diffusing capacity of lung for carbon monoxide (DLCO) at Week 4. The secondary objective of the study is to evaluate the safety of Treamid tablet, 50 mg and pharmacokinetics (PK).

NCT04527354
Conditions
  1. SARS-CoV-2 Infection
  2. Fibrosis Lung
Interventions
  1. Drug: Treamid
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinically significant changes include a relative ≥ 10% increase in FVC or a relative increase in FVC within the range from ≥ 5% to <10% and a relative ≥ 15% in DLCO

Measure: Rate of clinically significant change in FVC and/or DLCO at Week 4 relative to the baseline value

Time: Day 1- Day 28

Secondary Outcomes

Measure: Change in distance covered for 6 minutes (6MWD) at Weeks 2 and 4 from the baseline value (based on 6-minute walk test)

Time: Day 1- Day 28

Measure: Change in the score of the Borg scale at Weeks 2 and 4 from the baseline value (based on the 6-minute walk test)

Time: Day 1- Day 28

Measure: Change in forced expiratory volume for the first second (FEV1) according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

Time: Day 1- Day 28

Measure: Change in FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

Time: Day 1- Day 28

Measure: Change in FEV1/FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

Time: Day 1- Day 28

Measure: Change in DLCO according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

Time: Day 1- Day 28

Measure: Change in Total Lung Capacity (TLC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

Time: Day 1- Day 28

Measure: Change in Functional Residual Capacity (FRC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

Time: Day 1- Day 28

Description: Classification of lung damage includes the following stages: CT-0 (norm), CT-1 (< 25% of lung damage), CT-2 (25-50% of lung damage), CT-3 (50-75% of lung damage), CT-4 (> 75% of lung damage)

Measure: The rate of reduction in the lung damage degree based on the computed tomography (CT) at Week 4 relative to the baseline value

Time: Day 1- Day 28

Measure: Change in mMRC Dyspnea Score in Week 1, Week 2, Week 3, and Week 4 from the baseline value

Time: Day 1- Day 28

Measure: Change in the overall score of the KBILD Questionnaire at Week 2 and Week 4 relative to the baseline value

Time: Day 1- Day 28

Other Outcomes

Measure: The rate of adverse events (AEs)

Time: Day 1- Day 28

Measure: The rate of serious adverse events (SAEs)

Time: Day 1- Day 28

Description: Blood sampling for the PK study of the parameter Сtrough will be performed for all patients prior to administration of the Treamid / Placebo at Week 0, Week 2, and Week 4 visits.

Measure: Residual concentration Ctrough of the active substance of Treamid

Time: Day 1- Day 28
308 Efficacy and Safety of Using Convalescent Plasma for Treating Patients With COVID-19 Pneumonia Without Indication of Ventilatory Support

The COVID-19 pandemic has been spreading continuously, and in Brazil, until August 18, 2020, there have been more than 3,359,000 cases with more than 108,536 deaths, with daily increases. The present study proposes to evaluate the efficacy and safety of using convalescent plasma for treating patients with COVID-19 pneumonia without indication of ventilatory support.

NCT04528368
Conditions
  1. COVID-19
Interventions
  1. Biological: Convalescent plasma
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To evaluate the area under the curve of SARSCoV-2 viral load in nasopharyngeal and or oropharyngeal samples on days 0, 3, 6, 9, 12, 15, 18 and 15 after randomization.

Measure: Area under the curve of SARS-COV-2 viral load obtained from nasopharyngeal and /or oropharyngeal swabs.

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Secondary Outcomes

Description: The seven-point scale is as follows: Death 7 points; Hospital admission for mechanical ventilation plus additional organ support (eg, pressors, RRT, ECMO) = 6 points; Hospital admission for mechanical ventilation = 5 points; Hospital admission for non-invasive ventilation or high-flow oxygen therapy = 4 points; Hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation) = 3 points; Hospital admission but not requiring oxygen therapy = 2 points; Discharged with limitations of activities = 1 point; Discharged with no limitations of activities = 0 point;

Measure: Assessment of clinical improvement using an Ordinal Severity Scale

Time: 0, 7, 10, 14, 21 and 28 days

Measure: Evaluate oxygen saturation

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Measure: Evaluate oxygen supplementation

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Measure: Assess respiratory rate

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Measure: Evaluate the PaO2 / FiO2 ratio (for patients on mechanical mechanisms)

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Measure: Length of hospital stay

Time: 21 days

Measure: Length of stay in intensive care

Time: 21 days

Measure: Assess the rate of orotracheal intubation

Time: 21 days

Description: Quantification by ELISA the levels of 36 molecules determined simultaneously using the Human Cytokine Array Kit da R&D Systems (C5a, IL-4, IL-32 alpha, CD40 ligand, IL-5, CXCL10 / IP-10, G-CSF, IL-6, CXCL11 / I-TAC, GM-CSF, IL-8, CCL2 / MCP-1, CXCL1 / GRO alpha, IL-10, MIF, CCL1 / I-309, IL-12 p70, CCL3 / MIP-1 alpha, ICAM-1, IL-13, CCL4 / MIP-1 beta, IFN -gamma, IL-16, CCL5 / RANTES, IL-1 alpha, IL-17, CXCL12 / SDF-1, IL-1 beta, IL-17E, Serpin E1 / PAI-1, IL-1ra, IL-23, TNF-alpha, IL-2, IL-27 and TREM-1)

Measure: Change in the profile of cytokines/chemokines in both groups

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Measure: Presence of antibodies against SARS-CoV-2 in serum after convalescent plasma administration

Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

Measure: Death rate

Time: 7, 10, 14, 21 and 28 days

Measure: Rate of transfusion reactions to convalescent plasma infusion

Time: 21 days
309 Steroids and Unfractionated Heparin in Critically Ill Patients With Pneumonia From COVID-19 Infection. A Multicenter, Interventional, Randomized, Three Arms Study Design

SARS-CoV-2 infection seems to induce in most critical cases an excessive and aberrant hyper-inflammatory host immune response that is associated with a so-called "cytokine storm", moreover pro-thrombotic derangements of haemostatic system is another common finding in most severe forms of COVID19 infections, which may be explained by the activation of coagulative cascade primed by inflammatory stimuli, in line with what is observed in many other forms of sepsis. Targeting inflammatory responses exploiting steroids' anti-inflammatory activity along with thrombosis prevention may be a promising therapeutic option to improve patients' outcome. Despite the biological plausibility, no good evidence is available on the efficacy and safety of heparin on sepsis patients, and many issues have to be addressed, regarding the proper timing, dosages and administration schedules of anticoagulant drugs. The primary objective is to assess the hypothesis that an adjunctive therapy with steroids and unfractionated heparin (UFH) or with steroids and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill patients with pneumonia from COVID- 19 infection compared to low molecular weight heparin (LMWH) alone. Mortality will be measured at 28 days. The study is designed as a multicenter, national, interventional, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned in a ratio 1:1:1 to one of the three treatment groups: LMWH group, LMWH+steroids or UFH+steroid group. A possible result showing the efficacy of the composite treatment in reducing the mortality rate among critically ill patients with pneumonia from COVID-19 infection will lead to a revision of the current clinical approach to this disease.

NCT04528888
Conditions
  1. Covid19
  2. SARS-CoV Infection
  3. Pneumonia, Viral
  4. Coagulopathy
Interventions
  1. Drug: Enoxaparin
  2. Drug: Methylprednisolone
  3. Drug: unfractionated heparin
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Critical Illness
HPO:Pneumonia

Primary Outcomes

Description: All-cause mortality at day 28, defined as the comparison of proportions of patients death for any cause at day 28 from randomization.

Measure: All-cause mortality at day 28

Time: Day 28 from randomization

Secondary Outcomes

Description: All-cause mortality at ICU discharge, defined as the comparison of proportions of patients death for any cause at ICU discharge.

Measure: All-cause mortality at ICU discharge

Time: from randomization to ICU discharge, censored at day 30

Description: All-cause mortality at Hospital discharge, defined as the comparison of proportions of patients death for any cause at hospital discharge

Measure: All-cause mortality at hospital discharge

Time: from randomization to ICU discharge, censored at day 90

Description: Occurrence of rescue administration of high-dose steroids or immune-modulatory drugs

Measure: Need of rescue administration of high-dose steroids or immune-modulatory drugs

Time: from randomization to ICU discharge, censored at day 28

Description: Occurrence of new organ dysfunction during ICU stay. Organ dysfunction is defined as a Sequential Organ Failure Assessment (SOFA) score ≥3 for the corresponding organ occurring after randomization.

Measure: New organ dysfunction during ICU stay

Time: From randomization to ICU discharge, censored at day 28

Description: Grade of organ dysfunction during ICU stay, grade of dysfunction is measured with Sequential Organ Failure Assessment (SOFA) score daily from randomization to day 28 or ICU discharge.

Measure: Grade of organ dysfunction during ICU stay

Time: From randomization to ICU discharge, censored at day 28

Description: Total number of days between ICU discharge and day 28. If death occurs during the ICU stay before day 28 the ICU free days calculation will be 0. The ICU readmission before day 28 after randomization will be considered.

Measure: ICU free days at day 28

Time: From randomization to day 28

Description: Occurrence of new infections including bacterial infections, fungal infections by Candida, Aspergillus, and viral reactivations including Adenovirus, Herpes Virus e Cytomegalovirus

Measure: Occurrence of new infections

Time: from randomization to day 28

Description: Total number of days that patient is alive and free of ventilation between randomisation and day 28. Ventilation is considered as positive pressure ventilation, either invasive or non-invasive. Periods of assisted breathing lasting less than 24 hours for surgical procedures will not count against the ventilation free days calculation.

Measure: Ventilation free days at day 28

Time: From randomization to day 28, censored at hospital discharge

Description: Total number of days that patient is alive and free of vasopressors between randomisation and day 28.

Measure: Vasopressors free-days at day 28

Time: From randomization to day 28, censored at hospital discharge

Description: Occurrence of switch from non-invasive to invasive mechanical ventilation

Measure: Switch from non-invasive to invasive mechanical ventilation

Time: from randomization to ICU discharge, censored at day 28

Description: Total number of hours from start of non-invasive to invasive ventilation to switch to invasive ventilation

Measure: Delay from start of non-invasive ventilation to switch to invasive ventilation

Time: from randomization to ICU discharge, censored at day 28

Description: Adverse events occurred from randomization to day 28. Events that are part of the natural history of the primary disease process or expected complications of critical illness will not be reported as adverse events.

Measure: Occurrence of protocol related adverse events

Time: From randomization to day 28

Description: Occurrence of objectively confirmed venous thromboembolism, stroke or myocardial infarction

Measure: Occurrence of venous thromboembolism, stroke or myocardial infarction

Time: from randomization to ICU discharge, censored at day 28

Description: Occurrence of major bleeding defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death)

Measure: Occurrence of major bleeding (safety end point)

Time: from randomization to ICU discharge, censored at day 28

Description: Occurrence of clinically relevant non-major bleeding defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, or 100 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug.

Measure: Occurrence of clinically relevant non-major bleeding (safety end point)

Time: from randomization to ICU discharge, censored at day 28

Other Outcomes

Description: Mean arterial pressure will be measured in millimeters of mercury

Measure: Mean arterial pressure

Time: Daily from inclusion until ICU discharge, censored day 28

Description: hearth rate will be measured in beats per minute

Measure: hearth rate

Time: Daily from inclusion until ICU discharge, censored day 28

Description: respiratory rate will be measured in breaths per minute

Measure: respiratory rate

Time: Daily from inclusion until ICU discharge, censored day 28

Description: diuresis will be measured daily in milliliters of urine output in the previous 24 hours

Measure: diuresis

Time: Daily from inclusion until ICU discharge, censored day 28

Description: systemic body temperature will be measured in celsius degrees

Measure: systemic body temperature

Time: Daily from inclusion until ICU discharge, censored day 28

Description: fluid balance will be measured in milliliters of fluids input and output in the previous 24 hours

Measure: fluid balance

Time: Daily from inclusion until ICU discharge, censored day 28

Description: Haemoglobin will be measured in mg/dl

Measure: Haemoglobin concentration

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: platelets count will be measured in U 10^3/mm^3

Measure: platelets count

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: white blood cells count will be measured in U per 10^9/L

Measure: white blood cells count

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: troponin will be measured in µg/L

Measure: troponin

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: coagulative function will be measured with parameters INR, PT, aPTT

Measure: coagulative function

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: D-dimer will be measured in µg/ml

Measure: D-dimer

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: anti-thrombin will be measured as a percentage

Measure: anti-thrombin

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: liver function will be assessed through measurement of AST, ALT in U/L

Measure: Liver function

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: Bilirubin will be measured in mg/dL

Measure: Bilirubin

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: Creatinine will be measured in mg/dL

Measure: Creatinine

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: Blood cells count will be measured in Units per x 10^9/L of blood

Measure: Blood cells count

Time: daily from inclusion to ICU discharge (censored at day 28)

Description: C-reactive protein (CRP) will be measured in mg/dl

Measure: C-reactive protein (CRP)

Time: daily from inclusion to ICU discharge (censored at day 28)

Description: procalcitonin(PCT) wiull be measured in ng/ml

Measure: procalcitonin(PCT)

Time: daily from inclusion to ICU discharge (censored at day 28)

Description: interleukin 6 (IL-6) will be measured in pg/ml

Measure: interleukin 6 (IL-6)

Time: daily from inclusion to ICU discharge (censored at day 28)

Description: Ventilation mode will be cathegorized in spontaneous breathing, invasive or non invasive ventilation

Measure: Ventilation mode

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: inspired oxygen fraction will be measured in percentage of oxygen in inspired air

Measure: inspired oxygen fraction

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: Gas exchanges will be assessed by measurement of PaO2, PaCO2 in mmHg by arterial blood gas analysis

Measure: Gas exchanges

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: lactates will be measured in mMol/L

Measure: lactates

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: pH will be measured in pH scale

Measure: pH

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: oxygen saturation in blood will be measured in arterial and venous samples in percentage values

Measure: oxygen saturation in blood

Time: Daily from inclusion to ICU discharge (censored at day 28)

Description: New blood, respiratory and urinary-tract infections will be recorded

Measure: New infections

Time: From randomization to day 28

Description: Viral reactivation measured by CMV DNA titres will be recorded.

Measure: Viral reactivation

Time: From randomization to day 28

Description: Need of new renal replacement therapy (intermittent haemodialysis or continuous veno-venous hemofiltration) will be recorded.

Measure: Need of new renal replacement therapy

Time: from randomization to day 28

Description: Adjunctive treatment such as pronation cycles, Nitric Oxide or ECMO will be recorded

Measure: Adjunctive treatments

Time: from randomization to ICU discharge (censored at day 28);
310 Efficacy and Safety Study to Evaluate the Use of Nebulized Heparin in Patients With Severe Acute Respiratory Syndrome Covid-19 (SARS-CoV-2)

To evaluate the safety and efficacy of the use of inhalational heparin in patients with pulmonary compromise / pneumonia / SARS associated with COVID-19, laboratory with marked inflammation parameters, and prothrombotic state secondary to it (Fibrinogen, Ferritin and / or elevated D-Dimer) , from admission to hospitalization. The combination of inhalation heparin combined with prophylactic doses of LMWH could reduce the progression to severe forms of the disease, and consequently the need for intensive care units and mechanical ventilation.

NCT04530578
Conditions
  1. Covid19
  2. Pneumonia
Interventions
  1. Drug: Heparin sodium
  2. Drug: Enoxaparin
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Blood Gas criteria :PaO2 / FiO2 <200 (or the inability to maintain an SpO2 of at least 92% with a reservoir mask). Acute ventilatory failure (pH less than 7.35 with PaCO2 greater than 45 mmHg)

Measure: Percentage of patients requirement mechanical ventilation

Time: 15 days

Secondary Outcomes

Description: Mean every 48 hours PaO2 to FiO2 ratio

Measure: Percentage of patients with PaO2 to Fi02 ratio > 300

Time: 7 days

Description: To compare the lengths of hospital-stay

Measure: Lengths of hospital-stay

Time: Days 60

Description: All cause mortality

Measure: Mortality rate

Time: 30 days
311 Randomized, Open, Parallel, Single-center, Non-inferiority Clinical Trial, With an Active Control Group, Comparing Two Oral Prednisone Regimens With the Aim of Optimizing the Therapeutic Strategy in Patients With Organizing Pneumonia Post-COVID-19 Infection

Background: Based on data from the 2003 SARS-COVID pandemic, other serious lung infections, and patients with respiratory distress, it is estimated that 10-30% of patients with severe SARS-COVID-2 pneumonia may present as a sequel an organized pneumonia. The treatment of this complication is not well defined. The use of oral corticosteroids is mandatory to avoid a possible evolution to pulmonary fibrosis, however, the doses to be administered and the duration of treatment are unknown as there is no study specifically aimed at solving this doubt. Many authors advocate high-dose treatment regimens for a minimum of six months, as proposed for cryptogenic organized pneumonia. However, there is a question whether in non-idiopathic cases of organized pneumonia, less intense treatment could resolve the disease. Hypothesis: The use of a less intensive prednisone regimen may be sufficient for therapeutic control in patients with post-COVID-19 organizing pneumonia, in relation to the established standard regimen Simplicity of the procedures: The objective of the NORCOVID study is to identify the optimal treatment regimen with corticosteroids in post-COVID19 patients diagnosed with NO. Specifically, the primary objective of this multicenter randomized trial is to evaluate whether treatment with a less intensive regimen of corticosteroids produces a non-inferior therapeutic effect than the established control regimen. Secondary objectives are to evaluate the effect of treatment on secondary efficacy variables and on safety. DLCO, respiratory function tests, 6MWT test, need for rescue, radiological tests, complications, mortality and the WHO ordinal scale will be evaluated.

NCT04534478
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Drug: Prednisone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The main variable will be the change in pulmonary diffusion, in terms of predicted DLCO (%), between the baseline value and that obtained at 6 months, comparing the two treatment groups, adjusting for the baseline value using a repeated measures model with random effects (mixed model for repeated measurements.

Measure: Change in pulmonary diffusion.

Time: Six Months
312 Randomized Trial, Anti-inflammatory Effect of Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia

There are several clinical studies that mention the benefits of treatment with low-dose radiation therapy to patients with COVID 19, so this study protocol will be started to determine if there is clinical improvement with treatment and low-dose radiation therapy. to all the lung.

NCT04534790
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Radiation: Low Dose Radiotherapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: improvement of oxygen saturation

Measure: Clinical improvement

Time: 7 days

Secondary Outcomes

Description: improvement in acute phase reactants and simple tomography

Measure: improvement of laboratory and imaging parameters

Time: 7 -14 days
313 Convalescent Plasma as Potential Therapy for Severe COVID-19 Pneumonia

To determinate feasibility, safety and outcome with convalescent plasma in patients with severe COVID-19 penumonia

NCT04535063
Conditions
  1. Covid19 Pneumonia
Interventions
  1. Biological: COVID19 convalescent plasma infusion
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: number of subjects surviving at 28 days from plasma infusion

Measure: 28 days survival

Time: 28 days

Secondary Outcomes

Description: comparison of clinical efficacy according antibodies levels

Measure: efficacy of plasma infusion according to antibodies levels in the infuse bags

Time: 28 days

Description: we will search if clinical efficacy is better when the earlier the infusion is decided

Measure: clinical efficacy of plasma infusion according to frame time from symptoms onset and hospitalization

Time: 28 days

Description: WHO clinical scale is a measure of patient progression through the health-care system with 1 point asymptomatic patient and 10 patient dead

Measure: change in clinical WHO ordinal scale from 1 to 10 points

Time: 14 days
314 A Multicenter, Randomised, Controlled, Open Label Trial on the Efficacy and Safety of Asunercept for Patients With Severe COVID-19 Disease

This is an open-label, randomized, phase II study with the main objective to investigate the effectiveness and safety of an investigational drug (APG101; International Nonproprietary Name: asunercept) in patients with severe COVID-19 disease. The study aims to decrease overall and SARS-CoV-2 associated pneumonia mortality in patients with COVID-19 as well as to decrease the percentage of patients admitted to Intensive Care Unit (ICU), decrease the need to supply oxygen to patients, reduce the number of days patients are hospitalized in ICU and/or on the ward, decrease the number of days required to obtain a negative result in the PCR (Polymerase Chain Reaction, a laboratory technique that allows the amplification of small fragments of DNA to detect the presence of the virus) test for COVID-19 and decrease the levels of markers that indicate pneumonia.

NCT04535674
Conditions
  1. COVID-19 Induced Pneumonia
  2. Covid19
Interventions
  1. Biological: Asunercept
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The primary endpoint is time to clinical improvement which is defined as time from randomisation to an (sustained) improvement of at least one category on two consecutive days compared to the status at randomisation measured on a nine-category ordinal scale (proposed by WHO).

Measure: Time to sustained improvement of one category (i.e. two consecutive days) from randomisation

Time: Day 1-29

Secondary Outcomes

Description: Time to discharge or to a NEWS of ≤2 and maintained for 24 hours, whichever occurs first Change from baseline

Measure: Efficacy according to the National Early Warning Score (NEWS)

Time: Day 1-29

Description: Oxygenation free days until day 29 Incidence and duration of new oxygen use during the trial

Measure: Oxygenation

Time: Day 1-29

Description: Ventilator free days until day 29 Incidence and duration fo new mechanical ventilation use during the trial

Measure: Ventilation

Time: Day 1-29

Description: Duration of hospitalisation Length of ICU stay (in days)

Measure: Hospitalisation - Length

Time: Day 1-29

Description: Proportion of patients admitted to ICU

Measure: Hospitalisation - Proportion on ICU

Time: Day 1-29

Description: 15-day, 29-day all-cause mortality

Measure: Mortality

Time: Day 1-29
315 Utility of Low Doses of Corticosteroids and Cyclosporine Combined With Enoxaparin, in Patients With COVID-19 Pneumonia at the ISSSTE Regional Hospital, Puebla, During the Contingency Period Due to the SARS-Cov2 Pandemic

Methods: Single-center pilot study included PCR+ SARS-CoV2-patients, hospitalized from April to May 2020 in Puebla, Mexico. Comparative treatment with steroids plus CsA or steroids. Mild, moderate or severe pneumonia was measured by clinical, laboratory tests, lung damage score by computed tomography, and score for clinical improvement. Death rate was evaluated at 28 days.

NCT04540926
Conditions
  1. COVID 19 Pneumonia
Interventions
  1. Drug: Cyclosporin A
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Improvement of patients, defined by the following parameters: lower oxygen requirements (2 liters per minute, or less), absence of fever by three consecutive days, respiratory rate <22, a decrease of 50% or more in the C reactive protein on admission, and length of hospital stay.

Measure: Number of days to clinical improvement until hospital discharge or death.

Time: 28 days.
316 Evaluation of the Safety and Outcomes of Outpatient Management With Mild to Moderate COVID-19 Pneumonia (PneumoCoV-Ambu)

The purpose of this study is to evaluate the strategy of investigators for outpatients SARS-CoV-2 moderate pneumonia management in terms of efficacy and patient safety. The investigators ultimate goal is to validate first wave management strategy in order to support the investigators future approach in the event of a second wave, and spare the hospital resources by safely keeping at home as many patients as possible.

NCT04542044
Conditions
  1. Covid19
  2. Pneumonia
Interventions
  1. Other: management strategy of outpatient with mild to moderate SARS-CoV-2 pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Secondary hospitalization(s) or death COVID-19 related

Time: 30 to 60 days from diagnosis

Secondary Outcomes

Description: severity of COVID-19 disease on a 7-points ordinal scale (1: not hospitalized, no limitation of activities; 2: not hospitalized, limitation of activities; 3: hospitalized, not requiring supplementary oxygen; 4: hospitalized, requiring supplementary oxygen; 5: hospitalized, on non-invasive mechanical ventilation; 6: hospitalized, on invasive mechanical ventilation or ECMO; 7: death),

Measure: severity of COVID-19 disease

Time: 30 to 60 days from diagnosis

Description: Satisfaction Survey of outpatient management

Measure: patient satisfaction with management strategies

Time: 30 to 60 days from diagnosis

Description: estimation of saved costs compared with a strategy of hospitalization of all COVID-19 related pneumonia cases.

Measure: Saved costs

Time: 30 days
317 A Phase 1/2 Open Label, Multicenter, Single Arm Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Single Dose Kamada Anti-SARS-CoV-2 in COVID-19 Hospitalized Patients With Pneumonia

Evaluate the safety pharmacokinetics and pharmacodynamics (PK/PD)of a single dose of Kamada anti-severe acute respiratory syndrome (SARS)- CoV-2 in patients hospitalized with COVID-19 caused pneumonia

NCT04550325
Conditions
  1. Covid19
  2. Pneumonia, Viral
Interventions
  1. Biological: Kamada Anti-SARS-CoV-2
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Record adverse events, serious adverse events, and deaths

Measure: Adverse events, serious adverse events, and deaths

Time: 14 days

Description: Record adverse events, serious adverse events, and deaths

Measure: Adverse events, serious adverse events, and deaths

Time: 28 days

Secondary Outcomes

Description: Measurement of the area under the curve of anti SARS CoV-2 immunoglobulin

Measure: AUC0-7 of Anti SARS CoV-2 antibodies

Time: 7 days

Description: Evaluate virus neutralization activity of patient's plasma

Measure: Neutralization activity

Time: 7 days

Other Outcomes

Description: Time patient spent in hospital

Measure: Duration of Hospitalization

Time: 84 days

Description: Score on the 6 point ordinate scale

Measure: Clinical status on the 6 point ordinate scale

Time: 84 days
318 Evaluation of a Chest X-Ray AI Neural Network (RadGen SARS-CoV2 Detection System) for the Detection of RT-PCR Confirmed SARS-Cov2 Covid-19 Pneumonia

This study investigates the diagnostic performance of an AI algorithm in the detection of COVID-19 pneumonia on chest radiographs.

NCT04561024
Conditions
  1. Covid19
Interventions
  1. Diagnostic Test: AI model
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Performance (accuracy, sensitivity, specificity, false-positive rate (FPR), false-negative rate (FNR), and Area Under the Curve (AUC)) of the AI model in detection of COVID-19 pneumonia on their baseline CXR using RT-PCR and historical controls as gold standard in a multi-center / multi-national cohort.

Measure: Diagnostic Performance of AI model

Time: 9 months
319 A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of EG-HPCP-03a Compared to Dexamethasone in Patients With Moderate/Severe (Non-intubated, Non-mechanical Ventilation) COVID-19 Pneumonia

To study signals of efficacy and safety of a currently available dosage form (IM) of EG-HPCP-03a in reducing the severity of respiratory disease in patients hospitalized with SARS-CoV-2 virus.

NCT04561180
Conditions
  1. Pneumonia as One of the Lung Complications Caused by SARS-CoV-2 Infection
Interventions
  1. Drug: EG-HPCP-03a
  2. Drug: EG-HPCP-03a Placebo
  3. Drug: Standard of Care
  4. Drug: Dexamethasone
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Patients will be assessed for COVID-19 Ordinal Scale for Clinical Improvement scores and respiratory status throughout the study

Measure: The proportion of patients alive and without respiratory failure

Time: First dose date to 28 days treatment dosing period
320 Nitazoxanide for Moderate to Severe COVID-19 Pneumonia: a Multicenter, Randomized, Placebo-controlled, Double-Blind Clinical Trial

Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 500 Hospitalized patients with pneumonia derived from COVID-19 (Coronavirus Disease-19), either confirmed by RT-PCR (Real Time polymerase chain reaction), or suggested by typical findings on the computed tomography scan symptomatic. Experimental group: nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: placebo 8/8 hours for 5 days.

NCT04561219
Conditions
  1. Covid19
  2. Corona Virus Infection
  3. Pneumonia, Viral
Interventions
  1. Drug: Nitazoxanide
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Compare the intubation rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by percentage.

Measure: Orotracheal intubation rate

Time: 14 days

Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed free of mechanical ventilation, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

Measure: Mechanical ventilation free days

Time: 14 days

Secondary Outcomes

Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the hospital, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

Measure: Hospitalisation days

Time: 14 days

Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the ICU, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

Measure: ICU days

Time: 14 days

Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed with the support of oxygen nasal cannula, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

Measure: Intranasal oxygen support days

Time: 14 days

Description: Compare the mortality rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

Measure: Mortality rate

Time: 14 days

Description: Reduction in the duration of fever of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

Measure: Days with fever

Time: 14 days

Description: Reduction in the duration of cough of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

Measure: Days with cough

Time: 14 days

Description: Reduction in the duration of dyspnea of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

Measure: Days with dyspnea

Time: 14 days

Description: Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations.

Measure: Radiologic findings

Time: Day1

Description: Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations.

Measure: Radiologic findings

Time: Day7

Description: Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations.

Measure: Cardiologic findings

Time: Day1

Description: Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations.

Measure: Cardiologic findings

Time: Day7

Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: C-reactive protein - absolute number

Time: Day 1

Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: C-reactive protein serum levels

Time: Day 3

Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: C-reactive protein serum levels

Time: Day 7

Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Lactate dehydrogenase (LDH) serum levels

Time: Day 1

Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Lactate dehydrogenase (LDH) serum levels

Time: Day 3

Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Lactate dehydrogenase (LDH) serum levels

Time: Day 7

Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Troponin serum levels

Time: Day 1

Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Troponin serum levels

Time: Day 3

Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Troponin serum levels

Time: Day 7

Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Electrolytes serum levels

Time: Day 1

Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Electrolytes serum levels

Time: Day 3

Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Electrolytes serum levels

Time: Day 7

Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Glucose serum levels

Time: Day 1

Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Glucose serum levels

Time: Day 3

Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Glucose serum levels

Time: Day 7

Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Renal function

Time: Day 1

Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Renal function

Time: Day 3

Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Renal function

Time: Day 7

Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Coagulogram

Time: Day 1

Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Coagulogram

Time: Day 3

Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Coagulogram

Time: Day 7

Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Liver function panel

Time: Day 1

Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Liver function panel

Time: Day 3

Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Liver function panel

Time: Day 7

Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Ferritin

Time: Day 1

Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Ferritin

Time: Day 3

Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Ferritin

Time: Day 7

Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: D-dimer

Time: Day 1

Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: D-dimer

Time: Day 3

Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: D-dimer

Time: Day 7

Description: To evaluate blood cell count of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, for 7 days; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Blood cell count

Time: 7 days

Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Inflammatory mediators

Time: Day 1

Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Inflammatory mediators

Time: Day 3

Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

Measure: Inflammatory mediators

Time: Day 7

Other Outcomes

Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by percentage.

Measure: Adverse events - percentage

Time: Day 14

Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by absolute number.

Measure: Adverse events - absolute number

Time: Day 14

Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.

Measure: Treatment discontinuation rate - absolute number

Time: Day 14

Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.

Measure: Treatment discontinuation rate - percentage

Time: Day 14
321 A Randomized, Double Blind, Placebo-controlled, Phase 2 Clinical Trial to Investigate the Efficacy and Safety of 2 Doses of NuSepin® Intravenous Infusion in COVID-19 Pneumonia Patients

A randomized, double blind, placebo-controlled, phase 2 clinical trial to investigate the efficacy and safety of 2 doses of NuSepin® intravenous infusion in COVID-19 pneumonia patients

NCT04565379
Conditions
  1. COVID19 Pneumonia
Interventions
  1. Drug: NuSepin® 0.1 mg
  2. Drug: NuSepin® 0.2 mg
  3. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Difference in Time to Clinical Improvement (TTCI) between the 2 treatments and the placebo group (in days)

Time: Day 29

Secondary Outcomes

Measure: Percentage of patients with CRP < 10 mg/L or < 30% decreases from baseline

Time: Day 15 and Day 29

Description: Minimum value being 1, Maximum value being 6. Smaller the number, better the clinical status & outcome

Measure: Clinical Status assessed by the six-category ordinal scale at fixed time points

Time: Day 1, 4, 9, 15 and 29

Measure: Time to complete clinical remission OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours

Time: Up to Day 29

Measure: All-cause mortality

Time: Up to Day 29

Measure: Duration (days) of mechanical ventilation

Time: Up to Day 29

Measure: Duration (days) of extracorporeal membrane oxygenation

Time: Up to Day 29

Measure: Duration (days) of supplemental oxygenation

Time: Up to Day 29

Measure: Length of hospital stay (days)

Time: Up to Day 29

Measure: Length of ICU stay (days)

Time: Up to Day 29

Measure: Number of incidence of treatment emergent adverse events (TEAEs) in 3 treatment groups

Time: Day 15 and Day 29

Other Outcomes

Measure: Serum level of TNF-α in pg/ml

Time: Day 0, 4, 9, 15 and 29

Measure: Serum level of IL-1β in pg/ml

Time: Day 0, 4, 9, 15 and 29

Measure: Serum level of IL-6 in pg/ml

Time: Day 0, 4, 9, 15 and 29

Measure: Serum level of IL-8 in pg/ml

Time: Day 0, 4, 9, 15 and 29
322 Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of EC-18 in Preventing the Progression of COVID-19 Infection to Severe Pneumonia or ARDS

A trial of EC-18 in patients with mild/moderate pneumonia due to COVID-19

NCT04569227
Conditions
  1. Covid19 Pneumonia
Interventions
  1. Drug: EC-18
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Proportion of patients alive and free of respiratory failure through at Day 28

Time: 28 days

Secondary Outcomes

Measure: Probability of progression of mild pneumonia patients to severe pneumonia or ARDS within 28 days

Time: 28 days

Measure: Assessment of all-cause mortality

Time: 28 days

Description: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20L/min with a fraction of delivered oxygen ≥ 0.5) Non-invasive positive pressure ventilation Extracorporeal membrane oxygenation

Measure: Respiratory failure defined based on resource utilization requiring at least 1 of the following:

Time: 28 days

Measure: Proportion of patients alive and free of invasive mechanical ventilation at a pre-specified timepoint

Time: 28 days

Measure: Proportion of patients alive and discharged from the hospital at a pre-specified timepoint

Time: 28 days

Measure: Lengths of ICU stay

Time: 28 days

Measure: Lengths of alive and respiratory failure-free days

Time: 28 days

Measure: Proportion of patients with objective measures of improvement (returning to room air) at time points (days 7, 14, and 28)

Time: 7, 14, and 28 days

Description: o Check for changes in symptoms on a daily basis for 28 days compared to the baseline at day 1

Measure: Confirmation of changes in subject's subjective clinical symptoms (e.g., patient questionnaire)

Time: 28 days
323 Effectiveness of an Exercise Re-training Program on Dyspnea in Patients After Acute Respiratory Distress Syndrome Secondary to Severe COVID-19 Pneumonia in Post-ICU

Dyspnea is defined by a subjective sensation of respiratory discomfort, the intensity of which varies according to the terrain, the anamnesis and the cause. Resuscitation is associated with many causes of dyspnea, including initial distress, mechanical ventilation, or after-effects following the pathology and its management. Respiratory distress is the most severe form of impaired lung function. It is the first cause of hospitalization in intensive care. This distress, indicative of the failure of the respiratory system, is always severe and potentially fatal. It therefore constitutes an absolute therapeutic emergency. Dyspnea is often the revealing symptom of the condition and the urgency surrounding its management is an additional factor of concern for the patient. As a result, dyspnea is a pejorative element associated with severity or even death.

NCT04569266
Conditions
  1. Dyspnea
Interventions
  1. Other: specific exercise rehabilitation treatment
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea
HPO:Dyspnea Pneumonia Respiratory distress

Primary Outcomes

Description: Multidimensional Dyspnea Profile (MDP) scale assessment of dyspnea

Measure: Evaluate the effect of exercise rehabilitation on post-ICU dyspnea

Time: Day 1

Description: Multidimensional Dyspnea Profile (MDP) scale assessment of dyspnea

Measure: Evaluate the effect of exercise rehabilitation on post-ICU dyspnea

Time: 3 Months

Secondary Outcomes

Description: Assessment of dyspnea on the Modified Medical Research Council (mMRC) scale

Measure: Evaluate the effect of exercise rehabilitation on functional dyspnea

Time: Day 1

Description: Assessment of dyspnea on the Modified Medical Research Council (mMRC) scale

Measure: Evaluate the effect of exercise rehabilitation on functional dyspnea

Time: 3 Months

Description: Short-Form Quality of Life Assessment (SF-12)

Measure: Evaluate the effect of stress rehabilitation on quality of life

Time: Day 1

Description: Short-Form Quality of Life Assessment (SF-12)

Measure: Evaluate the effect of stress rehabilitation on quality of life

Time: 3 Months
324 Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)

To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.

NCT04569877
Conditions
  1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
  2. COVID-19 Pneumonia
Interventions
  1. Drug: Molgramostim nebuliser solution
  2. Other: Placebo nebuliser solution
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Need for mechanical ventilation within 15 days after randomization

Measure: Mechanical ventilation

Time: During 15 days

Secondary Outcomes

Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.

Measure: Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale):

Time: At day 15 and day 29

Description: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] will be measured at day 0 (day before first dose), day 1-9, and day 15

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: At day 0 (day before first dose), day 1-9, and day 15

Description: Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98%

Measure: Oxygen supply

Time: At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15

Description: Clinical parameter (4 times daily): temperature (°C degree)

Measure: Clinical parameter: temperature

Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

Description: Clinical parameter (4 times daily): blood pressure (mmHg)

Measure: Clinical parameter: blood pressure

Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

Description: Clinical parameter (4 times daily): hear beat (beats per minute)

Measure: Clinical parameter: heart beat

Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

Description: Clinical parameter (4 times daily): respiratory rate (breaths per minute)

Measure: Clinical parameter: respiratory rate

Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

Description: Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage

Measure: Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)

Time: Max. 48 hours before day 0 and at day 8-9

Description: C-reactive protein test measures the amount of C-reactive protein in blood (mg/L)

Measure: Laboratory: C-reactive protein test

Time: At day 0, day 1-7, day 8-9 and day 15

Description: Ferritin test measures the amount of ferritin in the blood (ng/ml)

Measure: Laboratory: ferritin

Time: At day 0, day 1-7, day 8-9 and day 15

Description: Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml)

Measure: Laboratory: Interleukin-6

Time: At day 0, day 1-7, day 8-9 and day 15

Description: Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l)

Measure: Laboratory: procalcitonin

Time: At day 0, day 1-7, day 8-9 and day 15

Description: Occurrence of secondary bacterial pneumonia

Measure: Bacterial pneumonia

Time: At day 0, day 1-7, day 8-9 and day 15

Description: Days on vaso-active drugs in a 29-day period

Measure: Vaso-active drugs

Time: At day 29

Description: All-cause mortality

Measure: Mortality

Time: At day 29

Description: GM-CSF levels in serum

Measure: GM-CSF

Time: At day 0 and day 1-7
325 Open Clinical Trial of the Use of Antioxidants and Pentoxifylline as Adjuvant Therapy to Standard Therapy in Patients With and Without Septic Shock Secondary to COVID-19 Severe Pneumonia

Introduction: SARS-CoV2 infection produces severe pneumonia with pulmonary alveolar collapse. There is no specific treatment to date. In experimental models and humans with septic shock, there is a high production of nitric oxide (NO) and reactive nitrogen species (RNS) and can cause multiple organ failure. The administration of antioxidants such as n-acetylcysteine (NAC), vitamin C, melatonin, and vitamin E participate in increasing the intracellular content of GSH, ROS sequestration, protection of the lipids of cell membranes, cytosol proteins, nuclear DNA, mitochondrial and decrease LPO. Justification: as there is no specific antiviral therapy, the therapeutic options are limited, complications and mortality are high; It is intended to evaluate the effect of antioxidants on the storm outcome of the dysregulation of oxidative stress. Hypothesis: It is postulated that adjuvant therapy with antioxidants and Pentoxifylline reduces the use of ventilators in patients with or without septic shock secondary to severe SARS-COV2 pneumonia as decreases lipoperoxidation, and corrects dysregulation of oxidative stress by increasing the antioxidant capacity. Objectives: To evaluate whether it is possible to avoid intubation or decrease assisted mechanical ventilation days, improve oxidative stress dysregulation in patients with SARS-COV2 infection with severe pneumonia with or without septic shock. Methodology: Quasi-experimental, open analytical, prospective, and longitudinal study (before-after). In patients over 18 years of age who are admitted to the CITIBANAMEX Center with or without septic shock secondary to severe SARS-COV2 pneumonia. There will be two groups: 1) patients without septic shock and 2) patients with septic shock secondary to severe pneumonia due to SARS-COV2. A single antioxidant will be applied following the clinical decision tree (NAC, Vit C, Vit E, melatonin) more Pentoxifylline orally or by orogastric tube for a total of 5 days from the start of the protocol. APACHE II will calculate the risk, SOFA, MEXSOFA, measurements of IL-8, vitamin C, NO3 / NO2, LOP, total antioxidant capacity will be carried out at baseline and 48 hours. SOFA will be calculated for seven days, in addition to days of hospitalization, days of mechanical ventilation. It was evaluated 28 days after discharge by telephone.

NCT04570254
Conditions
  1. Pneumonia, Viral
  2. Covid19
  3. ARDS
  4. Oxidative Stress
Interventions
  1. Drug: Vitamin C
  2. Drug: Vitamin E
  3. Drug: Melatonin
  4. Drug: N-acetyl cysteine
  5. Drug: Pentoxifylline
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: It will be evaluated whether secondary to SARS-COV2 pneumonia, the outcome of the patient is dead.

Measure: Death from any cause

Time: From admission to discharge, up to 30 days.

Description: The percentage of patients with SARS-COV2 pneumonia in whom orotracheal intubation was avoided will be evaluated.

Measure: Percentage of patients who required orotracheal intubation

Time: From admission to discharge, up to 1 week

Description: It will be evaluated if it is possible to reduce the days of mechanical ventilation

Measure: Assisted mechanical ventilation

Time: From admission to discharge, up to 1 week

Description: The number of days of stay in the intensive care unit will be evaluated.

Measure: Stay in an intensive care unit

Time: From admission to discharge, up to 1 week

Secondary Outcomes

Description: For the measurement of lipid peroxidation, 50 µL of CH3-OH with 4% BHT plus a phosphate buffer pH 7.4 was added to 100 µL of plasma. The mixture was vigorously vortexed for 5 seconds and subsequently incubated in a water bath at 37 ° C for 30 minutes. 1.5 mL of 0.8 M tribarbituric acid was added to the sample, which was incubated in a water bath with boiling temperature for one hour. After this time and to stop the reaction, the sample was placed on ice; 1 mL 5% KCl was added to each sample, as was 4 mL of n-butanol; The sample was vortexed for 30 seconds and centrifuged at 4000 rpm at room temperature for 2 min. Subsequently, the butanol phase was extracted, and the absorbance at 532 nm was measured. The calibration curve was obtained using tetra ethoxy propane as a standard.

Measure: Measure lipoperoxidation in basal and post-therapy samples

Time: Baseline and 5 days post-dose

Description: 100 mL of plasma was suspended in 1.5 mL of a reaction mixture prepared as follows: 300 mM of acetate buffer with pH 3.6, 20 mM of ferric chloride hexahydrate, and 10 mM of 2,4,6-Tris-2- Pyridyl-s-triazine dissolved in 40 mM hydrochloric acid in a ratio 10: 1: 1 v / v, respectively. The mixture was vigorously vortexed for 5 seconds. It was incubated at 37 ° C for 15 min in the dark. The absorbance was measured at 593 nm. The calibration curve was obtained using Trolox

Measure: Evaluation of the total antioxidant capacity

Time: Baseline and 5 days post-dose

Description: For the measurement of NO3- / NO2-, 100 µl of plasma were added 100 µL of a 10% solution of ZnSO4, 100 µL of 0.5 N NaOH and 700 µl of tridestated water. It was shaken vigorously and centrifuged at 10,000 rpm for 5 minutes. To the resulting supernatant, Griess reagent (200 µL of 1% sulfanilamide and 200 µL of 1% N- (1-naphthyl) ethylenediamine hydrochloride) was added and incubated for 10 min protected from light at room temperature. The coloration developed after incubation was measured at an analytical wavelength of 540 nm in a double beam UV-Vis spectrometer (DW2000, SLM-Aminco, Urbana, Illinois, USA). The calibration curve was performed with a KNO3 stock solution (Spectrum Quality Products, Inc., Gardena CA) in a concentration range from 0.001 nM to 10 nM.

Measure: Oxidative and antioxidant stress

Time: Baseline and 5 days post-dose

Description: Measurements will be made using the Sequential Organ Failure Assessment (SOFA) every 24 hours. With a minimum score of 0-1 which translates a mortality in initial score and the highest of 0%. The maximum score of more than 14 translates a mortality of 95.2% in the initial evaluation and 89.7% in the highest evaluation.

Measure: Effect of antioxidant therapy at the level on organ failure secondary to SARS-COV2

Time: From day 0 to day 7 post antioxidant dose.

Description: Measurements will be made using the Mexico Sequential Organ Failure Assessment (MEXSOFA) every 24 hours. highest evaluation. Patients with an initial MEXSOFA score of 9 points or less calculated during the first 24 hours after admission to the ICU had a mortality rate of 14.8%, while those with an initial MEXSOFA score of 10 points or more had a mortality rate. 40% mortality rate. The MEXSOFA score at 48 h was also associated with mortality: patients with a score of 9 points or less had a mortality rate of 14.1%, while those with a score of 10 points or more had a rate of 50% mortality.

Measure: Effect of antioxidant therapy at the level on organ failure secondary to SARS-COV2

Time: From day 0 to day 7 post antioxidant dose.
326 Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia (a Phase I Feasibility Trial)

The purpose of this study is to document the feasibility and tolerability of low dose thoracic radiotherapy in patients with WHO level 5 COVID 19 infections.

NCT04572412
Conditions
  1. Covid19
Interventions
  1. Radiation: Low dose Radiotherapy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Feasibility to recruit to the study.

Measure: Feasibility of Recruitment

Time: 6 months

Description: Proportion of patients with no decline in PaO2/FiO2 ratio (P/F Ratio) at 48 hours after each fraction of radiotherapy

Measure: Tolerability of Low dose Radiotherapy

Time: 48 hours

Secondary Outcomes

Description: The number of patients who withdraw from the study

Measure: Withdrawal

Time: 6 months

Description: The number of Grade 4 or higher CTCAE v5 (apart from asymptomatic lymphopenia) adverse events reported

Measure: Adverse events

Time: 1 month

Description: Ability to perform lymphocyte subset, IL-6, and IL-10 analysis at baseline and 7 days post last fraction of radiotherapy

Measure: Feasibility of biochemical analysis

Time: 1 week
327 A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

NCT04574869
Conditions
  1. Acute Lung Injury
  2. ALI
  3. COVID-19
Interventions
  1. Drug: RLS-0071
  2. Drug: RLS-0071
  3. Drug: Placebo
  4. Drug: RLS-0071
  5. Drug: RLS-0071
  6. Drug: Placebo
MeSH:Pneumonia Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
HPO:Pneumonia

Primary Outcomes

Measure: Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.

Time: Through study completion at Day 28 following last dose.

Secondary Outcomes

Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose apparent total body clearance for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

Time: Through study completion at Day 28 following last dose.

Measure: Overall survival.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.

Time: Days on ventilation while in the hospital through study completion at Day 28.

Measure: Incidence of transfer to the ICU.

Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.

Measure: Duration of hospitalization after treatment (days).

Time: Through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

Time: Through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

Time: Through study completion at Day 28 following last dose.

Measure: Duration of requirement for supplemental oxygen after treatment (days).

Time: Through study completion at Day 28 following last dose.

Measure: PaO2/FiO2

Time: Through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Description: Dialysis will be assessed by the investigator with CTCAE's latest version.

Measure: Incidence and duration after treatment (days) of dialysis.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Measure: Levels of complement activity (eg, CH50).

Time: Through study completion at Day 28 following last dose.

Measure: Levels of C1q (free and bound to RLS-0071).

Time: Through study completion at Day 28 following last dose.
328 Risk Factors, Prognosis and Findings by Computed Tomography in Patients Infected by COVID-19 and Its Association With Severity.

In the SARS-CoV2 pandemic, imaging studies proved its diagnostic utility to determine the severity of lung involvement. Computed tomography (CT) is a state-of-the-art study proven to be a highly sensitive diagnostic test complemented by RT-PCR testing to determine the disease and the degree of severity. In March 2020, the Dutch Society of Radiology developed a standardized assessment scheme for COVID-19 lung disease, called CO-RADS. This system proposes a level of suspicion of pulmonary involvement of COVID-19, based on the simple chest tomography findings. The level of suspicion ranges from very low (CO-RADS 1) to very high (CO-RADS 5), with two additional categories involving a technically deficient study (CO-RADS 0) and a positive RT-PCR test for SARS -CoV-2 known before tomography (CO-RADS 6). For its part, acute respiratory damage secondary to SARS-COV2 pneumonia causes acute respiratory distress syndrome, which warrants immediate medical attention. During the evaluation and triage of patients with suspected or confirmed SARS-COV2 infection, it is a challenge for health personnel given that the severity and clinical presentation is highly variable. The patient's risk stratification is carried out using previously established and validated risk scales and is a fundamental tool for making clinical decisions. Some of the risk indices and scales have been developed and used in the pandemic epicenters, such as China and Europe. Useful for the clinician is the national early warning scale (NEWS 2), severe disease risk assessment score (COVID-GRAM), the rapid severity index for COVID-19 (qCSI), evaluation score of Modified sequential organ failure (mSOFA), the sepsis-induced coagulopathy score (SIC), the ROX index as a predictor of success to the high-flow nasal cannula. The evaluation of the risk of thrombotic complications such as the Padua risk, of cardiac complications such as QT segment prolongation, through the Tisdale risk score. Risk stratification is essential in the current COVID-19 pandemic situation; upon admission, the clinician will discern if the patient requires in-hospital medical treatment, the risk of severe disease, and progression to assisted mechanical ventilation. This work aims to establish whether the severity of the findings identified by cardiac tomography upon admission and the risk established by the different established prognostic indices.

NCT04577105
Conditions
  1. Covid19
  2. ARDS
  3. Pneumonia, Viral
  4. Computed Tomography
Interventions
  1. Diagnostic Test: Simple chest tomography
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: CO-RADS will categorize the level of suspicion of COVID-19. Very low (CO-RADS 1) to very high (CO-RADS 5), with two additional categories involving a technically deficient study (CO-RADS 0) and a positive RT-PCR test for SARS-CoV- 2 known before tomography (CO-RADS 6).

Measure: Assessment of the level of suspicion of SARS-CoV2 infection

Time: At hospital admission

Description: It will be a semi-quantitative assessment of lung lobe lesions' extent considering five lobes (upper right lobes, middle lobe, lower right lobe, upper left lobe, and lower left lobe). Each of these lobes, depending on their condition, is scored from 1 to 5, with 1 <5%, 2 from 5 to 25%, 3> 25 to 50%, 4 from> 50 to 75% and the number 5 greater than 75%. With this, it is grouped into mild affection from 1 to 5 points, moderate from 5 to 15 points, and greater than 15 points as severe affection

Measure: Evaluate the severity degree of pulmonary affection by chest computed tomography

Time: At hospital admission

Description: The requirement for orotracheal intubation and the start of assisted mechanical ventilation after admission will be evaluated

Measure: Percentage of patients requiring endotracheal intubation

Time: From admission to discharge, up to 1 week

Description: Patients who present fatal descent during hospitalization will be evaluated.

Measure: Death from any cause

Time: From admission to discharge, up to 1 week

Secondary Outcomes

Description: The evaluation of multiple organ failure secondary to sepsis will be carried out using the mSOFA scale, which can predict in-hospital mortality and 30 days, with a minimum score of 0-7 that translates mortality of 0% and a score greater than 11 translates mortality of 58%.

Measure: Modified Sequential Organ Failure Assessment (mSOFA)

Time: At hospital admission

Description: The sepsis-induced coagulopathy score scale (SIC) refers to the diagnosis of coagulopathy when the score is greater than 4 or the INR is greater than or equal to 3.

Measure: Sepsis-induced coagulopathy (SIC)

Time: At hospital admission

Description: A score of 0-4 confers a low risk; on the contrary, a score of more than 7 gives a high risk.

Measure: National Early Warning Scale (NEWS 2)

Time: At hospital admission

Description: It establishes three risk groups: the mild one with a risk of critical illness of less than 1.7% and the high risk of more than 40.4%.

Measure: COVID-GRAM severe illness risk score

Time: At hospital admission

Description: A score less than or equal to 3 gives a low risk with a critical illness risk of 4%, while a score of 10-12 gives a high risk and a critical illness probability of 57%.

Measure: Rapid Severity Index for COVID-19 (qCSI)

Time: At hospital admission

Description: A ratio of 6-8 translates mild physiological stress, while a ratio of more than 18 a severe physiological stress level.

Measure: Neutrophil-Lymphocyte Ratio (NLR)

Time: At hospital admission

Description: The gradient Aa O2 = [(FiO2) × (Atmospheric pressure - Pressure of H2O) - (PaCO2 / 0.8)] - PaO2 of ABG is calculated and a normal gradient with age is estimated with the following formula: Estimate of normal gradient = (Age / 4) + 4. The gradient is increased in conditions such as ARDS, PE, and cardiac failure.

Measure: Alveolar-arterial gradient of oxygen

Time: At hospital admission

Description: Required criteria (must have all three of the following): Timing within 1 week of clinical insult or new/worsening respiratory symptoms, Chest XR shows bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules Respiratory failure not fully explained by cardiac failure/fluid overload Risk factor (one of the following): Risk factor for ARDS present (e.g. pneumonia, trauma, sepsis, pancreatitis). Objective assessment (Echo) excludes hydrostatic edema. Severity (based on oxygenation, select one of the following): Mild: PaO₂/FiO₂ >200 to ≤300 mmHg with PEEP OR CPAP ≥5 cm H₂O, Moderate: PaO₂/FiO₂ >100 to ≤200 mmHg with PEEP ≥5 cm H₂O and Severe: PaO₂/FiO₂ ≤100 mmHg with PEEP ≥5 cm H₂O

Measure: Berlin Criteria for Acute Respiratory Distress Syndrome

Time: At hospital admission
329 A Phase I/II Dose-escalation Multi Center Study to Evaluate the Safety of Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in coronaviruS pnEumonia and/or Lymphopenia

This is a phase I/II clinical trial using adoptive cell therapy with NK cells or memory T cells in patients affected by COVID-19. Severe cases with COVID-19 present a dysregulated immune system with T cell lymphopenia, specially NK cells and memory T cells, and a hyper-inflammatory state. This clinical trial proposes the use of cell therapy for the treatment of patients with worse prognosis due to SARS-CoV-2 infection (those with pneumonia and/or lymphopenia). This is an innovative and a non-pharmacological intervention.

NCT04578210
Conditions
  1. Corona Virus Infection
Interventions
  1. Biological: T memory cells and NK cells
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Lymphopenia
HPO:Lymphopenia Pneumonia

Primary Outcomes

Description: Any grade 3 or higher toxicity with an attribution of definitely or probably related to the infusion of the cells and any lower grade toxicity that increases to a grade 3 or higher as a direct result of the cell infusion.

Measure: Occurrence of DLTs in all patients during the study treatment, until 21 days after cell infusion and the MTD

Time: 3 months
330 Randomised Multi-arm Trial of Ruxolitinib (RUX) and Fostamatinib (FOS) for COVID-19 Pneumonia

The Multi-arm trial of Inflammatory Signal Inhibitors for COVID-19 (MATIS) study is a two-stage, open-label, randomised controlled trial assessing the efficacy of ruxolitinib (RUX) and fostamatinib (FOS) individually, compared to standard of care in the treatment of COVID-19 pneumonia. The primary outcome is the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Patients are treated for 14 days and will receive follow-up assessment at 7, 14 and 28 days after the first study dose. Patients with mild or moderate COVID-19 pneumonia will be recruited. Initially, n=171 (57 per arm) patients will be recruited in Stage 1. Following interim analysis to assess the efficacy and safety of the treatments, approximately n=285 (95 per arm) will be recruited during Stage 2.

NCT04581954
Conditions
  1. Coronavirus
  2. Covid19
  3. Pneumonia
Interventions
  1. Drug: Ruxolitinib
  2. Drug: Fostamatinib
  3. Other: Standard of care
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: All-cause mortality

Time: Day 14

Measure: Number and proportion of patients requiring invasive ventilation

Time: Day 14

Measure: Number and proportion of patients requiring non-invasive ventilation (CPAP and high flow nasal oxygen)

Time: Day 14

Secondary Outcomes

Measure: All-cause mortality

Time: Day 28

Measure: Number and proportion of patients requiring invasive ventilation or extracorporeal membrane oxygenation (ECMO)

Time: Day 14, 28

Measure: Number and proportion of patients requiring non-invasive ventilation including continuous positive airway pressure (CPAP) or high flow nasal oxygen

Time: Day 14, 28

Measure: Number and proportion of patients requiring renal replacement therapy

Time: Day 14, 28

Measure: Number and proportion of patients experiencing venous thromboembolism events

Time: Day 14, 28

Measure: Length of stay

Time: Day 14, 28

Measure: Number and proportion of serious adverse events and discontinuations

Time: Day 14, 28

Description: Scale range from 0 (uninfected) to 9 (dead)

Measure: Absolute change in pneumonia severity on the modified WHO COVID-19 Ordinal Scale

Time: Day 14, 28
331 D-dimer Adjusted Versus Therapeutic Dose Low-molecular-weight Heparin in Patients With COVID-19 Pneumonia

evaluation of the efficacy and safety of D-dimer adjusted heparin versus therapeutic dose heparin in patients with COVID-19 Pneumonia.

NCT04584580
Conditions
  1. Coronavirus Disease (COVID)19
Interventions
  1. Drug: low-molecular-weight heparin
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: All cause mortality

Measure: mortality

Time: Until patient is discharged or up to 4 weeks whichever comes first

Description: clinical signs supported by radiological evidence of arterial thrombosis or venous thromboembolism (e.g. venous or arterial duplex and CT scan of the chest with pulmonary angiography)

Measure: occurrence of venous and/or arterial thrombosis

Time: Until patient is discharged or up to 4 weeks whichever comes first

Secondary Outcomes

Description: calculation of sepsis induced coagulopathy (SIC) score

Measure: occurrence of Sepsis-induced coagulopathy

Time: Until patient is discharged or up to 4 weeks whichever comes first

Description: Calculation of partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/ FIO2) ratio

Measure: Occurrence of adult respiratory distress syndrome (ARDS)

Time: Until patient is discharged or up to 4 weeks whichever comes first

Description: Calculation of sequential organ failure (SOFA) score

Measure: Occurrence of sepsis

Time: Until patient is discharged or up to 4 weeks whichever comes first

Description: occurrence of respiratory failure detected by arterial blood gases analysis

Measure: ICU admission and need for mechanical ventilation

Time: Until patient is discharged or up to 4 weeks whichever comes first
332 Prone Position to Improve Oxygenation in COVID-19 Patients Outside Critical Care (PRONE-COVID Study)

Prone positioning is known to improve the PaO2/FiO2 ratio and reduce mortality in patients with ARDS managed in the critical care setting. Therefore, it is incorporated into regular clinical practice of managing patients with ARDS in critical care and is being used as such in the COVID-19 outbreak. Given that prone positioning is recommended by the Intensive Care Society in non-ventilated patients with COVID-19, there is an urgent need to better understand the physiological effects of prone positioning in such cases. Furthermore, the translation and applicability of such a low-cost non-invasive intervention in a wider group of patients with pneumonia not specific to covid-19 infection, is an important consideration that merits investigation. This single-centred observational study conducted at Cambridge University Hospitals NHS Foundation Trust aims to improve understanding of physiological effects of prone positioning in non-ventilated patients with COVID-19 and a control group of patients with non-COVID-19 related pneumonia. The study also aims to incorporate a small subset of patients, with an approximately even spread of COVID-19 and non-COVID cases, which allows for an additional exploratory descriptive report on prone positioning over a 24-hour period. This study proposes that prone positioning improves oxygenation in non-ventilated patients with pneumonia (COVID-19 related or not) requiring supplemental oxygen managed outside of the critical care setting.

NCT04589936
Conditions
  1. Pneumonia
  2. Covid19
Interventions
  1. Procedure: Prone positioning
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Oxygenation measured by peripheral saturations in relation to inspired oxygen (FiO2) when patient is prone versus a supine or lateral position using a Masimo device

Measure: Peripheral Oxygen saturation

Time: 1 year (June 2021)

Secondary Outcomes

Description: To evaluate effects of prone position versus supine or lateral position on derived measures of oxygenation (Pa02:Fi02 ratio calculated from formulae) in relation to inspired oxygen.

Measure: PaO2 :FiO2 ratio calculated from formulae

Time: 1 year (June 2021)

Description: Effects of prone versus supine or lateral position on respiratory rate

Measure: Respiratory rate measured with Masimo device

Time: 1 year (June 2021)

Description: Effects of prone versus supine or lateral position on heart rate

Measure: Heart rate measured with Masimo device

Time: 1 year (June 2021)

Description: Effects of prone versus supine or lateral position on blood pressure

Measure: Blood pressure measured with Masimo device

Time: 1 year (June 2021)

Description: To evaluate whether prone position reduces patient reported severity of breathlessness assessed by visual assessment score.

Measure: Patient reported severity of breathlessness on a continuous linear scale of 0 to 10cm (10cm being the most severe)

Time: 1 year (June 2021)

Description: To evaluate patient tolerability of prone position assessed by visual assessment score.

Measure: Patient tolerability of prone position on a continuous linear scale of 0 to 10cm (10cm being the most unacceptable)

Time: 1 year (June 2021)

Description: To evaluate investigator experience of delivering prone positioning in this study by free text question responses.

Measure: Investigator experience of delivering prone positioning

Time: 1 year (June 2021)

Description: To evaluate the natural position of patients (with the aid of position sensors) who are encouraged to position themselves prone over a 24-hour period (which include sleep) and relationship with oxygenation

Measure: To assess patient's peripheral oxygen saturation

Time: 1 year (June 2021)
333 Myeloid Cells in Patients With Covid-19 Pneumonia

The purpose of this study is to analyze in depth the relationship of myeloid cell subpopulations during infection by Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), the virus mediating Covid-19. Myeloid cells include neutrophils, monocytes and dendritic cells, each divided into subpopulations with different functions in immune defense and immune pathologies. The study is based on the following hypotheses: - Infection and the interferon response to infection may induce hyperactive or immunosuppressive differentiation of myeloid cells, that may be treated by specific inhibitors. - Some myeloid cell subpopulations currently identified in our laboratories might be markers for Covid-19 prognosis. - Alternative receptors may be present on myeloid cells, inducing the cytokine storm, a target for therapy. - The expression of Interferon (IFN) receptor and IFN responding genes on myeloid cells and on respiratory epithelial cells may correlate with prognosis and indicate potential treatment targets. - Interferon responses are known to be skewed during Covid-19, but some IFN subtype polymorphisms may correlate with prognosis and these subtypes migt be supplemented or inhibited for therapy.

NCT04590261
Conditions
  1. Covid-19; SARS-Cov2
Interventions
  1. Other: Blood sampling
  2. Other: Nasal Brushing
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Cytometric analysis of surface and intracellular molecules to identify myeloid cell sub-populations and define their function in vivo

Measure: Myeloid cell sub-population phenotype

Time: Month zero-month 36

Secondary Outcomes

Description: Cell culture and cytometric and analyte analysis of their functions, including IFN production

Measure: Myeloid cell functions

Time: Month zero-month 36

Description: Transcriptomic and proteomic analysis of the functions of myeloid cell subtypes

Measure: Myeloid cell transcriptomic and proteomic study

Time: Month zero-month 36

Description: Single cell RNA sequencing of the nasal brush products

Measure: Transcriptomic study of nasal epithelial cells

Time: Month zero-month 36

Description: High sensitivity detection by state-of-the art ELISA type methods

Measure: Plasma analyte concentration measurement

Time: Month zero-month 36
334 Safety, Tolerability and Efficacy of GLS-1027 in the Prevention of Severe Pneumonitis Caused by SARS-CoV-2 Infection

This clinical trial will evaluate the safety, tolerability and efficacy of GLS-1027 in the prevention of severe pneumonitis caused by SARS-CoV-2 infection

NCT04590547
Conditions
  1. Pneumonitis
  2. SARS-CoV Infection
Interventions
  1. Drug: GLS-1027
  2. Drug: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Incidence of serious adverse events relative to treatment group

Time: 56 days

Measure: Incidence of progression to WHO Classification of ≥6 to include intubation with mechanical ventilation, need for ECMO, or death relative to treatment group

Time: 56 days

Secondary Outcomes

Measure: Assess the number of days requiring ICU care relative to treatment group

Time: 56 days

Measure: Assess the number of days of mechanical ventilation relative to treatment group

Time: 56 days
335 Long-term Follow-up Findings of Inpatients for COVID-19 Pneumonia Related to Lung Functions, Radiology and Exercise Capacity

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus (SARS-CoV-2) that can progress to severe multiorgan disease requiring hospitalization. The medium and long-term impact in survivors of COVID-19 on lung function, imaging by thoracic CT, exercise capacity, and health-related quality of life and the relation of these parameters remains to be determined.

NCT04599998
Conditions
  1. Covid19
Interventions
  1. Diagnostic Test: spirometry, thoracic CT, CPET, 6 minute walking test, SF-36 questionnaire
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: in ml

Measure: Forced vital capacity (FVC)

Time: at 6-12 months after discharge

Description: DLCO (%predicted); DLCO/alveolar volume- DLCO/VA (%predicted)

Measure: Lung diffusion capacity for carbon monoxide (DLCO)

Time: at 6-12 months after discharge

Description: m

Measure: 6-minute walk test distance

Time: at 6-12 months after discharge

Description: scores range between 0 and 100 with higher scores indicating a better HRQoL

Measure: Short-form 36 questionnaire (SF-36)

Time: at 6-12 months after discharge

Description: from incremental Cardiopulmonary exercise test (% of predicted)

Measure: Oxygen uptake at peak exercise

Time: at 6-12 months after discharge

Description: from incremental Cardiopulmonary exercise test (L/L)

Measure: Minute-ventilation/carbon dioxide output during exercise

Time: at 6-12 months after discharge

Description: from incremental Cardiopulmonary exercise test (measured with 10-point categorical Borg scale

Measure: Dyspnea during exercise

Time: at 6-12 months after discharge

Description: lung parenchymal abnormalities as percentage of occupied lung

Measure: Thoracic CT findings

Time: in hospital and at 6-12 months after discharge

Description: in ml and %predicted

Measure: Forced expiratory volume in 1 second

Time: at 6-12 months after discharge

Description: in %

Measure: FEV1/FVC ratio

Time: at 6-12 months after discharge

Description: in %

Measure: Forced vital capacity %predicted (FVC%)

Time: at 6-12 months after discharge

Secondary Outcomes

Description: Recorded separately as present or absent) mortality (recorded as present or absent)

Measure: Signs and symptoms

Time: in hospital and at 6-12 months after discharge

Description: in days

Measure: Time to hospital discharge

Time: in hospital

Description: in days

Measure: ICU discharge

Time: in hospital

Description: in days

Measure: Weaning from intubation

Time: in hospital

Description: in days

Measure: Weaning from supplemental oxygen

Time: in hospital

Description: in days

Measure: Weaning from noninvasive mechanical ventilation

Time: in hospital

Description: recorded as present or absent

Measure: Mortality

Time: in hospital and at 6-12 months after discharge
336 The Extended Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in COVID-19 Associated Two-Sided Pneumonia

Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection. According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes. This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.

NCT04602442
Conditions
  1. Covid19
  2. SARS-CoV-2 PNEUMONIA
  3. COVID-19
Interventions
  1. Drug: EXO 1 inhalation
  2. Drug: EXO 2 inhalation
  3. Drug: Placebo inhalation
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial

Measure: Number of participants with non-serious and serious adverse events during trial

Time: through study, an average of 2 months

Description: Safety assessments such as adverse events during the inhalation procedures will be registered.

Measure: Number of participants with non-serious and serious adverse during inhalation procedure

Time: 10 days during inhalation procedures

Secondary Outcomes

Description: Measure and compare time to clinical recovery and clinical discharge compare to placebo.

Measure: Time to clinical recovery (TTCR)

Time: up to 2 months

Description: Concentration of SpO2 by Pulse oximetry device during procedures and compare to placebo.

Measure: SpO2 concentration changes

Time: up to 2 months

Description: Chest imaging changes for 30 days compared to placebo. Information on the percent of damaged lungs will be analyzed and reported.

Measure: Chest Imaging Changes

Time: Three times. At diagnosis, 10-14 days after treatment and 30 days after clinic discharge

Description: C-reactive protein (CRP, mg/L) concentration in the plasma will be measured. The result will be analyzed and compared in time.

Measure: Blood biochemistry (CRP)

Time: Baseline, day 5, 10, 20

Description: Procalcitonin concentration in plasma (ng/mL) will be measured. The result will be analyzed and compared in time.

Measure: Procalcitonin concentration

Time: Baseline, day 5, 10, 20

Description: Ferritin concentration in plasma (ng/mL) will be measured. The result will be analyzed and compared in time.

Measure: Ferritin concentration

Time: Baseline, day 5, 10, 20

Description: Creatinine concentration (umol/L) in plasma will be measured. The result will be analyzed and compared in time.

Measure: Creatinine concentration

Time: Baseline, day 5, 10, 20

Description: Urea concentration (mmol/L) in plasma will be measured. The result will be analyzed and compared in time.

Measure: Urea concentration

Time: Baseline, day 5, 10, 20
337 Pulmonary Involvement of Novel SARS-COV-2 Infection (COVID-19): Long-term Impact and Predictors of Possible Lasting Damage: Follow the Covid Study

In December 2019 the first case of human infection by a new coronavirus was identified, currently called SARS-COV-2 (Severe Acute Respiratory Syndrome - Coronavirus - 2), characterized by high contagiousness and the possibility of causing a severe acute respiratory distress syndrome from which its acronym derives and which caused the state of a global pandemic in a few months. The most frequent clinical manifestation of COVID-19 is pneumonia, which in about 20% of cases results in acute respiratory failure. Very few studies have so far addressed the problem of clinical and functional recovery in these patients, most of them just before or after discharge and none specifically focused on patients admitted for ARF. Indeed most of these investigations were limited to a specific field such as symptoms, pulmonary function and radiological changes. There are no guidelines for the follow-up of COVID-19 patients, despite the British Thoracic Society (BTS) has published a guidance for scheduling post-hospitalization assessments. Aim of this study is to describe the long term (6 to 12 months) evolution of lung involvement in patients discharged after an episode of ARF due to COVID-19, identifying possible factor associated to lasting clinical, functional or radiological abnormalities collecting data from hospital stay, 1-month after hospital discharge, 3-months after hospital discharge and 6-to-12-months after hospital discharge.

NCT04605757
Conditions
  1. SARS-COV-2 Pneumonia
Interventions
  1. Other: Clinical, functional and radiological lung involvement evolution
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: For long term clinical evolution of SARS-COV-2 pneumonia Investigators will evaluate the presence or absence of each of the following symptoms (yes/no respectively for presence/absence): dyspnea, fatigue, cough, fever, thoracic pain, nausea, diarrhea, dysgeusia. The presence of each of these symptoms will be collected at the time of the hospital stay due to COVID-19 (H) and at 1-month after hospital discharge followup visit (V1); at 3-months after hospital discharge followup visit (V2); at 6-to-12-months after hospital discharge followup visit (V3). V3 will be performed for study subjects that at V2 show clinical and/or functional and/or radiological abnormalities due to sequelae of COVID-19. Differences in terms of presence and type of each symptoms between H, V1, V2 and V3 will be evaluated.

Measure: Long term evolution of clinical involvement due to SARS-COV-2 pneumonia / symptoms

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.

Description: For long term clinical evolution of SARS-COV-2 pneumonia Investigators will collect respiratory rate (RR, breaths/minute) of study subjects collected during the hospital stay due to COVID-19 (H); at V1, V2and V3. Difference in RR between H, V1, V2 and V3 will be evaluated.

Measure: Long term evolution of clinical involvement due to SARS-COV-2 pneumonia / respiratory rate

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.

Description: Investigators will collect: partial pressure of oxygen [paO2, mmHg], partial pressure of carbon monoxide [paCO2 mmHg], emerged from blood gas exchange analysis performed during H, V1, V2 and V3. For each parameter (paO2, paCO2) the difference between value at H, V1,V2 and V3 will be evaluated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters/partial pressure of oxygen and partial pressure of carbon monoxide

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

Description: Investigators will collect: - ph [absolute value], emerged from blood gas exchange analysis performed during H, V1, V2 and V3. Difference between pH value at H, V1,V2 and V3 will be evaluated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters/ ph

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

Description: Investigators will collect: - oxygen saturation [SatO2, in %]), emerged from blood gas exchange analysis performed during H, V1, V2 and V3. Difference between SatO2 value at H, V1,V2 and V3 will be evaluated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters/ oxygen saturation

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

Description: Investigators will collect: - P/F ratio (ratio between the measured paO2 and fraction of inspired oxygen ratio) expressed in absolute ratio; emerged from blood gas exchange analysis performed during H, V1, V2 and V3. Difference between P/F ratio value at H, V1,V2 and V3 will be evaluated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters: P/F ratio

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

Description: Investigators will consider the following parameters: forced expiratory volume in the first second [FEV1,expressed in % of predicted value]; forced vital capacity [FVC, expressed in % of predicted value]; total lung capacity [TLC, expressed in % of predicted value]; residual volume [RV, expressed in % of predicted value]; collected through pulmonary function tests performed at V1, V2 and V3. For each parameter (FEV1, FVC, TLC, RV) the difference between value at V1,V2 and V3 will be evaluated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - pulmonary function tests/ forced expiratory volume in the first second; forced vital capacity; total lung capacity; residual volume

Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge

Description: Investigators will consider the following parameters: FEV1/FVC absolute ratio; RV/TLC absolute ratio; collected through pulmonary function tests performed at V1, V2 and V3. For each parameter (FEV1/FVC, RV/TLC) the difference between value at V1,V2 and V3 will be evaluated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - pulmonary function tests/ FEV1/FVC ratio and RV/TLC ratio

Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge

Description: Investigators will consider diffusing capacity of carbon monoxide (DLCO), expressed in % of the predicted value collected during V1, V2 and V3. Differences in terms of DLCO values between V1, V2 and V3 will be calculated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - diffusing capacity of carbon monoxide

Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge

Description: Investigators will consider 6 minute walking test [6MWT] distance, expressed in meters collected during V1, V2 and V3. Differences in terms of 6MWT distance between V1, V2 and V3 will be calculated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - six minute walking test distance

Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge.

Description: Investigators will consider the presence (yes/no) of desaturation at 6MWT (defined as a difference > 3% between baseline SatO2% and minimum SatO2% during test) collected during V1, V2 and V3. Differences in terms of presence of desaturation at 6MWT between V1, V2 and V3 will be calculated.

Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - presence of desaturation during six minute walking test

Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge.

Description: For long term radiological evolution of SARS-COV-2 pneumonia Investigators will consider: presence [yes/no] of consolidation and/or ground-glass opacities at chest X-ray and high resolution computed tomography (HRCT) of the lungs, presence/absence [yes/no] of lung abnormalities in lung ultrasound (LUS) evaluation, collected each during H, V1, V2 and V3. Differences between H,V1,V2 and V3 for each characteristics will be described.

Measure: long term evolution of radiological involvement due to SARS-COV-2 pneumonia

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.

Secondary Outcomes

Description: To identify possible factors associated or correlated to the persistency of clinical and/or functional and/or radiological long term lung involvement due to SARS-COV-2 pneumonia at V1, V2, V3, primary outcome measurements will be stratified according to: the presence [yes/no] of comorbidities (cardiovascular, chronic obstructive pulmonary disease, asthma, immunological disorders, solid cancer, hematological malignancy, diabetes mellitus, immunodepression); age (expressed in years, age≥60 versus age<60 years); sex (male versus female); hospital stay duration (expressed in days); acute respiratory failure duration (expressed in days); of study subjects.

Measure: identifying possible factors associated to the persistency of clinical, functional and radiological long term lung involvement due to COVID-19

Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.
338 Clinical Trial on the Safety and Efficacy of Regadenoson for Moderate to Severe COVID-19 Adult Patients

More than 17 million people have been infected and more than 677K lives have been lost since the COVID-19 pandemic. Unfortunately, there is neither an effective treatment nor is there a vaccination for this deadly virus. The moderate to severe COVID-19 patients suffer acute lung injury and need oxygen therapy, and even ventilators, to help them breathe. When a person gets a viral infection, certain body cells (inflammatory/immune cells) get activated and release a wide range of small molecules, also known as cytokines, to help combat the virus. But it is possible for the body to overreact to the virus and release an overabundance of cytokines, forming what is known as a "cytokine storm". When a cytokine storm is formed, these cytokines cause more damage to their own cells than to the invading COVID-19 that they're trying to fight. Recently, doctors and research scientists are becoming increasingly convinced that, in some cases, this is likely what is happening in the moderate to severe COVID-19 patients. The cytokine storm may be contributing to respiratory failure, which is the leading cause of mortality for severe COVID-19 patients. Therefore, being able to control the formation of cytokine storms will also help alleviate the symptoms and aid in the recovery of severe COVID-19 patients.

NCT04606069
Conditions
  1. COVID-19
  2. Lung Inflammation
Interventions
  1. Drug: Regadenoson
  2. Other: Placebo Control
MeSH:Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Respiratory failure is defined based on resource utilization requiring at least 1 of the following modalities: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation or CPAP Whether patient is on ECMO

Measure: Proportion of patients alive and free of respiratory failure through the 30-day trial.

Time: 30 Days

Secondary Outcomes

Description: We will collect blood samples of the regadenoson and placebo treated patients at the baseline, 30mins, 4 hours during drug infusion and 12 hour post drug infusion. It may also including the daily blood collected on normal standard care base. The inflammatory cytokines, including IL-1 beta, IL-6, IL-4, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ will be measured using the Luminex™ 100 Multi-analyte System at The UM SOM Cytokine Core Laboratory. The levels of of cytokines will be measure in picogram/milliliter (pg/ml).

Measure: Change of the levels of the inflammatory cytokines prior, during and post drug infusion.

Time: 30 days

Description: The same blood samples used in outcomes 2 will be used to measure the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 using gelatin zymography as described in our previous publications (Zhao et al, 2010 & 2011). The enzyme levels will be quantified using The Image Lab 5.1 software. The unit will be nanogram/ml (ng/ml).

Measure: Change of the levels of MMP-2 and MMP-9 prior, during and post drug infusion.

Time: 30 days
339 Prospective, Open-label, Randomized, Multi-Center Study for Safety and Efficacy Evaluation of Inhaled Nitric Oxide (NO) Given Intermittently to Adults With Viral Pneumonia

The purpose of this multi center, open label, randomized, study is to obtain information on the safety and efficacy of 150 ppm Nitric Oxide given in addition to the standard of care of patients with viral pneumonia

NCT04606407
Conditions
  1. Viral Pneumonia
  2. Nitric Oxide
  3. Respiratory Disease
  4. Pneumonia, Viral
  5. Inhaled Nitric Oxide
  6. Covid19
  7. SARS-CoV Infection
Interventions
  1. Device: LungFit™
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Aspiration Respiration Disorders Respiratory Tract Diseases
HPO:Pneumonia

Primary Outcomes

Description: Clinical safety will be assessed by incidence of Serious Adverse Events (SAEs)

Measure: incidence of Serious Adverse Events

Time: 30 days

Secondary Outcomes

Description: Time to fever resolution

Measure: fever resolution

Time: Baseline to 30 days

Description: Number of patients requiring admission to ICU

Measure: ICU admission

Time: Baseline to 30 days

Description: Time until patient no longer requires supportive oxygen

Measure: Oxygen support

Time: Baseline to 30 days

Description: b.d. Stable room air saturation of 93% and above or returning to baseline saturation, whichever is lower

Measure: Stable room air saturation

Time: Baseline to 30 days
340 Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide Early After Mild-to-severe COVID-19

Infection with severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) may be associated with diffuse alveolar damage and pulmonary vasculitis. Thus, it is likely that pulmonary function changes may be seen in COVID-19 survivors. The aim of the present study was to test that simultaneously-determined lung diffusing capacity for nitric oxide and carbon monoxide may be useful to detect post-viral diffusive gas exchange abnormalities early after mild-to-severe COVID-19-related pneumonias.

NCT04610554
Conditions
  1. COVID-19 Pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Changes of DLNO after SARS-CoV-2 infection

Measure: Lung diffusing capacity for nitric oxide (DLNO)

Time: At a time interval ranging from 15 to 189 days after two nasopharyngeal swabs negative for SARS-CoV-2

Secondary Outcomes

Description: Changes of DLco after SARS-CoV-2 infection

Measure: Lung diffusing capacity for carbon monoxide (DLco)

Time: At a time interval ranging from 15 to 189 days after two nasopharyngeal swabs negative for SARS-CoV-2
341 Double-blind, Randomized, Controlled, Clinical Trial to Assess the Efficacy of Allogenic Mesenchymal Stromal Cells in Patients With Acute Respiratory Distress Syndrome Due to COVID-19

A double-blind, randomized, controlled, clinical trial to evaluate the efficacy and safety of MSC (mesenchymal stromal cells) intravenous administration in patients with COVID-induced ARDS compared to a control arm.

NCT04615429
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19 Pneumonia
Interventions
  1. Biological: Mesenchymal stromal cells
  2. Other: Placebo
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Primary endpoint

Measure: Change in the PaO2/FiO2* ratio from baseline to day 7 of treatment administration

Time: 7 days

Secondary Outcomes

Description: Secondary endpoint

Measure: All-cause mortality

Time: Days 7, 14, and 28 after treatment

Description: Secondary endpoint

Measure: Time to PaO2/FiO2 ratio greater than 200 mmHg

Time: 12 months

Description: Secondary endpoint. Categories: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities. Hospitalized, not requiring supplemental oxygen. Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high flow oxygen devices. Hospitalized, on invasive mechanical ventilation or ECMO . Death.

Measure: Clinical status on the World Health Organization ordinal scale

Time: Baseline, daily until day 14, and on day 28 after treatment

Description: Secondary endpoint

Measure: PaO2/FiO2 ratio

Time: Baseline and days 2, 4, 14 and 28 after treatment

Description: Secondary endpoint Sequential Organ Failure Assessment score (0-24)

Measure: SOFA score

Time: Baseline and days 2, 4, 7, 14 and 28 after treatment

Description: Secondary endpoint

Measure: Oxygen therapy-free days

Time: Day 28

Description: Secondary endpoint

Measure: Duration of hospitalization

Time: 12 months

Description: Secondary endpoint

Measure: Duration of ICU admission

Time: 12 months

Description: Secondary endpoint Proportion of patients with non-invasive ventilation

Measure: Incidence of non-invasive ventilation

Time: Day 28

Description: Secondary endpoint Proportion of patients with invasive mechanical ventilation

Measure: Incidence of invasive mechanical ventilation

Time: Day 28

Description: Secondary endpoint (number of days)

Measure: Duration of non-invasive ventilation

Time: Day 28

Description: Secondary endpoint (number of days)

Measure: Duration of invasive mechanical ventilation

Time: Day 28

Description: Secondary endpoint

Measure: Mechanical ventilation-free days

Time: Day 28

Description: Secondary endpoint

Measure: Survival rate

Time: 3 and 12 months.

Description: Secondary endpoint

Measure: Cumulative incidence SAEs, Grade 3 and 4 AEs, ADR and AEs of special interest.

Time: 12 months

Other Outcomes

Description: Exploratory endpoint Analytical markers (e.g., neutrophil and lymphocyte counts). Changes from baseline to set time points will be calculated.

Measure: Analytical endpoints

Time: Baseline and days 2, 4, 7, 14 and 28 after treatment
342 FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia

Vascular leakage following endothelial injury, responsible for interstitial and alveolar edema, is a major feature of pathogen induced acute lung injury. As acute respiratory distress syndrome (ARDS) due to pandemic Covid-19 is associated with more than 60% mortality, controlling vascular leakage may be a major target to decrease the mortality associated with the spreading of the disease in France. FX06, a drug under clinical development containing fibrin-derived peptide beta15-42, is able to stabilize cell-cell interactions, thereby reducing vascular leak and mortality in several animal models, particularly during lipopolysaccharide-induced and dengue hemorrhagic shock . A phase I study was conducted in humans, with no specific adverse event detected with a dose up to 17.5 mg/kg. In a phase II randomized multicentre double-blinded trial in 234 patients suffering from ST+ acute coronary syndrome, FX06 treated patients exhibited a 58% decrease in the early necrotic core zone. Importantly, adverse events were highly comparable between groups, indicating a high safety profile for the drug . Lastly, the drug was used as a salvage therapy in a patient exhibiting a severe ARDS following EBOLA virus infection . Altogether, those data indicate that FX06 is well tolerated in humans and is a potent regulator of vascular leakage. Our hypothesis here is that FX06 may decrease pulmonary vascular hyperpermeability during ARDS following SARS-CoV-2 infection, thereby improving gas exchanges and the outcome of infected patients.

NCT04618042
Conditions
  1. Ards
  2. Covid19
  3. Pneumonia
Interventions
  1. Drug: FX06
  2. Drug: Placebo of FX06
MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
HPO:Pneumonia

Primary Outcomes

Description: Assessed by transpulmonary thermodilution Transpulmonary thermodilution systems, part of the standard management in ICU, allow a direct evaluation of vascular hyperpermeability in the lungs using thermodilution technique. EVLWi is a reliable parameter, independently associated with mortality during ARDS

Measure: Change in extravascular lung water index (EVLWi)

Time: Between Day 1 and Day 7

Secondary Outcomes

Description: measured by transpulmonary thermodilution during 7 days

Measure: Evolution of daily extravascular lung water index (EVLWi)

Time: Between Day 1 and Day 7

Description: measured by transpulmonary thermodilution during 7 days

Measure: Evolution of daily cardiac index

Time: Between Day 1 and Day 7

Description: measured by transpulmonary thermodilution during 7 days

Measure: Evolution of global end-diastolic volume index

Time: Between Day 1 and Day 7

Description: measured by transpulmonary thermodilution during 7 days

Measure: Evolution of pulmonary vascular permeability index

Time: Between Day 1 and Day 7

Measure: Overall survival

Time: Day 30

Measure: Mortality rate in ICU and in hospital

Time: Through study completion an average of 2 months

Measure: Rate of withdraw or withhold life-sustaining treatments decision

Time: Day 30

Measure: Daily weight

Time: Between Day 1 and Day 7

Measure: Daily fluid balance

Time: Between Day 1 and Day 7

Description: Evolution of blood biological criteria (g/L)

Measure: Evolution of albuminemia

Time: Between Day 1 and Day 7

Measure: Duration of mechanical ventilation

Time: Day 30

Measure: Proportion of participants alive and off invasive mechanical ventilation

Time: Day 30

Measure: Evolution of Murray ARDS severity score

Time: Day 1 to day 15

Description: Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity

Measure: Evolution of radiological Weinberg score

Time: Day 1 to Day 30

Description: Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease

Measure: Evolution of pulmonary Sequential Organ Failure Assessment) score.

Time: Day 1 to day 15

Measure: Rate of rescue therapy with Veino-veinous V-ECMO

Time: Through study completion an average of 2 months

Description: Scale from 0 to 24, lower is better.

Measure: Evolution of SOFA (Sequential Organ Failure Assessment) score

Time: Day 15

Description: one or more SOFA sub-score >=3

Measure: Organ failure free days

Time: Day 15

Measure: Renal replacement therapy free days

Time: Day 30

Measure: Duration of renal replacement therapy free days

Time: Day 30

Measure: Nature and frequency of adverse events

Time: Through study completion an average of 2 months

Description: measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min

Measure: Evolution of FX06 concentration

Time: Day 1

Description: A test for immunogenicity will be performed on a serum sample at day 7 (2 days after the end of treatment administration) to detect any antibody against FX06. The assay will consist in a three-fold procedure, as recommended by the manufacturer. An initial screening assay will qualitatively measure antibodies to FX06. Samples deemed positive will be subject to a confirmatory assay, which will determine the specificity of the detected antibody against FX06. The third tier of the assay will consist in titre analysis to semi-quantitatively assess the antibody response.

Measure: Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure

Time: Day 7
343 Surfactant Protein D Levels in Covid-19 Infection: Case-Control Study

This study aims to provide some insight into the variation of SD-D protein levels in patients with Covid-19 (-) pneumonia, Covid-19 (+) pneumonia, and CT negative Covid-19 infection in comparison to the normal population through a larger number of cases. Objective of the study is to determine the serum surfactant protein D (SP-D) levels in Covid-19 pneumonia infection.

NCT04618861
Conditions
  1. Covid19
  2. Pneumonia
  3. Surfactant Protein Deficiency
MeSH:Infection Pneumonia Protein Deficiency
HPO:Pneumonia

Primary Outcomes

Description: First primary outcome is determining the serum surfactant protein D level changes in patient who have Covid-19 infection or pneumonia aganist healty controls.

Measure: Meassuring the serum surfactant protein D levels in patient who have Covid-19 infection or pneumonia.

Time: 2 months

Description: Determining the correlation between between serum surfactant protein D levels and demographic datas (age,gender), medical history, vital findings (fever, blood pressure, sPO2), laboratory findings (complete blood count; C-reactive protein (CRP), D-dimer, Ferritin and hsTnT parameters) and radiological findings, time to onset of symptoms, Comorbid diseases, hospitalization location of the patients (service or ICU), clinical scores (PSI and CURB65 scores), CT severity scores .

Measure: Analyzing the correlations between serum surfactant protein D levels and demographic,laboratory, clinical and radiological datas.

Time: 2 months
344 Determination of Biomarkers for the Prediction of Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia

The primary objective of this study is to demonstrate (at the time of admission) biomarkers of interest (Human Plasma BAK125 panel + interferon panel) for dexamethasone responders versus non-responders in SARS-CoV-2 hypoxemic pneumonia. The secondary objectives are to describe and compare between groups: - The number of days without mechanical ventilation - The need for mechanical ventilation - 28-day mortality - Progression towards acute respiratory distress syndrome (ARDS) - Change in the qSOFA score - Length of hospitalization - The change in the extent of lesions on thoracic computed tomography scan between inclusion and D7 (or the day of discharge from hospital if

NCT04619693
Conditions
  1. Pneumonia, Viral
  2. SARS-Cov-2
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Treatment failure is defined as the need to transfer the patient to intensive care for mechanical ventilation.

Measure: Treatment failure (yes/no)

Time: Hospital discharge (expected maximum of 28 days)

Secondary Outcomes

Description: PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc

Measure: Human Plasma BAK-125 proteomics profile

Time: Baseline (day 0)

Description: PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc

Measure: Human Plasma BAK-125 proteomics profile

Time: Day 7

Measure: Circulating blood interferon level

Time: Baseline (day 0)

Measure: Circulating blood interferon level

Time: Day 7

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of SpO2

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of FiO2

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of temperature (°C)

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of respiratory rate (cycles per minute)

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of pulse (bpm)

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of systolic blood pressure (mmHg)

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of diastolic blood pressure (mmHg)

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: Capillary glycemia will be measured at least twice per day throughout the initial hospitalization period.

Measure: A vector of repeated measures of capillary glycemia (g/L)

Time: Throughout initial hospitalization (expected maximum of 28 days)

Description: The Quick Sequential Organ Failure Assessment (qSOFA) score will be assessed at least twice per day throughout the initial hospitalization period. The quick Sepsis-related organ failure assessment (qSOFA) score ranges from 0 to 3 points, with '3' indicating the worst health state. It uses three criteria, assigning one point for low blood pressure (systolic blood pressure ≤100 mmHg), high respiratory rate (≥22 breaths per min), or altered mentation.

Measure: A vector of repeated measures of the qSOFA score

Time: Throughout initial hospitalization (expected maximum of 28 days)

Measure: Hemoglobin

Time: Baseline (day 0)

Measure: Hemoglobin

Time: Day 2

Measure: Hemoglobin

Time: Day 4

Measure: Hemoglobin

Time: Day 7 (or day of discharge if before day 7)

Measure: Platelet count

Time: Baseline (day 0)

Measure: Platelet count

Time: Day 2

Measure: Platelet count

Time: Day 4

Measure: Platelet count

Time: Day 7 (or day of discharge if before day 7)

Measure: White blood cell count

Time: Baseline (day 0)

Measure: White blood cell count

Time: Day 2

Measure: White blood cell count

Time: Day 4

Measure: White blood cell count

Time: Day 7 (or day of discharge if before day 7)

Measure: Neutrophil percentage

Time: Baseline (day 0)

Measure: Neutrophil percentage

Time: Day 2

Measure: Neutrophil percentage

Time: Day 4

Measure: Neutrophil percentage

Time: Day 7 (or day of discharge if before day 7)

Measure: Eosinophil percentage

Time: Baseline (day 0)

Measure: Eosinophil percentage

Time: Day 2

Measure: Eosinophil percentage

Time: Day 4

Measure: Eosinophil percentage

Time: Day 7 (or day of discharge if before day 7)

Measure: Basophil percentage

Time: Baseline (day 0)

Measure: Basophil percentage

Time: Day 2

Measure: Basophil percentage

Time: Day 4

Measure: Basophil percentage

Time: Day 7 (or day of discharge if before day 7)

Measure: Lymphocyte percentage

Time: Baseline (day 0)

Measure: Lymphocyte percentage

Time: Day 2

Measure: Lymphocyte percentage

Time: Day 4

Measure: Lymphocyte percentage

Time: Day 7 (or day of discharge if before day 7)

Measure: Monocyte percentage

Time: Baseline (day 0)

Measure: Monocyte percentage

Time: Day 2

Measure: Monocyte percentage

Time: Day 4

Measure: Monocyte percentage

Time: Day 7 (or day of discharge if before day 7)

Measure: Prothrombin rate (%)

Time: Baseline (day 0)

Measure: Prothrombin rate (%)

Time: Day 2

Measure: Prothrombin rate (%)

Time: Day 4

Measure: Prothrombin rate (%)

Time: Day 7 (or day of discharge if before day 7)

Measure: Activated partial thromboplastin time ratio

Time: Baseline (Day 0)

Measure: Activated partial thromboplastin time ratio

Time: Day 2

Measure: Activated partial thromboplastin time ratio

Time: Day 4

Measure: Activated partial thromboplastin time ratio

Time: Day 7 (or day of discharge if before day 7)

Measure: Fibrinogen (g/L)

Time: Baseline (Day 0)

Measure: Fibrinogen (g/L)

Time: Day 2

Measure: Fibrinogen (g/L)

Time: Day 4

Measure: Fibrinogen (g/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: D-Dimers (μg/mL)

Time: Baseline (Day 0)

Measure: D-Dimers (μg/mL)

Time: Day 2

Measure: D-Dimers (μg/mL)

Time: Day 4

Measure: D-Dimers (μg/mL)

Time: Day 7 (or day of discharge if before day 7)

Measure: Aspartate aminotransferase (ASAT; UI/L)

Time: Baseline (Day 0)

Measure: Aspartate aminotransferase (ASAT; UI/L)

Time: Day 2

Measure: Aspartate aminotransferase (ASAT; UI/L)

Time: Day 4

Measure: Aspartate aminotransferase (ASAT; UI/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Alanine aminotransferase (ALAT; UI/L)

Time: Baseline (Day 0)

Measure: Alanine aminotransferase (ALAT; UI/L)

Time: Day 2

Measure: Alanine aminotransferase (ALAT; UI/L)

Time: Day 4

Measure: Alanine aminotransferase (ALAT; UI/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Glucose (mmol/L)

Time: Baseline (Day 0)

Measure: Glucose (mmol/L)

Time: Day 2

Measure: Glucose (mmol/L)

Time: Day 4

Measure: Glucose (mmol/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Glycated haemoglobin (HbA1c; %)

Time: Baseline (Day 0)

Measure: Glycated haemoglobin (HbA1c; %)

Time: Day 2

Measure: Glycated haemoglobin (HbA1c; %)

Time: Day 4

Measure: Glycated haemoglobin (HbA1c; %)

Time: Day 7 (or day of discharge if before day 7)

Measure: Urea (mmol/L)

Time: Baseline (Day 0)

Measure: Urea (mmol/L)

Time: Day 2

Measure: Urea (mmol/L)

Time: Day 4

Measure: Urea (mmol/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Creatinine (µmol/L)

Time: Baseline (Day 0)

Measure: Creatinine (µmol/L)

Time: Day 2

Measure: Creatinine (µmol/L)

Time: Day 4

Measure: Creatinine (µmol/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time: Baseline (Day 0)

Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time: Day 2

Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time: Day 4

Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

Time: Day 7 (or day of discharge if before day 7)

Measure: Albumin (g/L)

Time: Baseline (Day 0)

Measure: Albumin (g/L)

Time: Day 2

Measure: Albumin (g/L)

Time: Day 4

Measure: Albumin (g/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: C reactive protein (CRP, mg/L)

Time: Baseline (Day 0)

Measure: C reactive protein (CRP, mg/L)

Time: Day 2

Measure: C reactive protein (CRP, mg/L)

Time: Day 4

Measure: C reactive protein (CRP, mg/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Lactate dehydrogenase (LDH, UI/L)

Time: Baseline (Day 0)

Measure: Lactate dehydrogenase (LDH, UI/L)

Time: Day 2

Measure: Lactate dehydrogenase (LDH, UI/L)

Time: Day 4

Measure: Lactate dehydrogenase (LDH, UI/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Hypersensitive troponin T (µg/L)

Time: Baseline (Day 0)

Measure: Hypersensitive troponin T (µg/L)

Time: Day 2

Measure: Hypersensitive troponin T (µg/L)

Time: Day 4

Measure: Hypersensitive troponin T (µg/L)

Time: Day 7 (or day of discharge if before day 7)

Measure: Ferritin (µg/L)

Time: Baseline (Day 0)

Measure: Ferritin (µg/L)

Time: Day 2

Measure: Ferritin (µg/L)

Time: Day 4

Measure: Ferritin (µg/L)

Time: Day 7 (or day of discharge if before day 7)

Description: CD4 refers to cluster of differentiation 4.

Measure: CD4 cell count

Time: Baseline (Day 0)

Description: CD4 refers to cluster of differentiation 4.

Measure: CD4 cell count

Time: Day 2

Description: CD4 refers to cluster of differentiation 4.

Measure: CD4 cell count

Time: Day 4

Description: CD4 refers to cluster of differentiation 4.

Measure: CD4 cell count

Time: Day 7 (or day of discharge if before day 7)

Description: CD8 refers to cluster of differentiation 8.

Measure: CD8 cell count

Time: Baseline (Day 0)

Description: CD8 refers to cluster of differentiation 8.

Measure: CD8 cell count

Time: Day 2

Description: CD8 refers to cluster of differentiation 8.

Measure: CD8 cell count

Time: Day 4

Description: CD8 refers to cluster of differentiation 8.

Measure: CD8 cell count

Time: Day 7 (or day of discharge if before day 7)

Measure: Natural killer cell count

Time: Baseline (Day 0)

Measure: Natural killer cell count

Time: Day 2

Measure: Natural killer cell count

Time: Day 4

Measure: Natural killer cell count

Time: Day 7 (or day of discharge if before day 7)

Measure: Activated T cell percentage

Time: Baseline (Day 0)

Measure: Activated T cell percentage

Time: Day 2

Measure: Activated T cell percentage

Time: Day 4

Measure: Activated T cell percentage

Time: Day 7 (or day of discharge if before day 7)

Measure: Change in SARS-CoV-2 real-time polymerase chain reaction cycle threshold

Time: Baseline to day 7 (or day of discharge if before day 7)

Measure: Change in SARS-CoV-2 IgG serology (% of control signal = PCS)

Time: Baseline to day 7 (or day of discharge if before day 7)

Measure: Change in SARS-CoV-2 IgM serology (% of control signal = PCS)

Time: Baseline to day 7 (or day of discharge if before day 7)

Measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 real time polymerase chain reaction

Time: Day 7 (or day of discharge if before day 7)

Measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgG serology

Time: Day 7 (or day of discharge if before day 7)

Measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgM serology

Time: Day 7 (or day of discharge if before day 7)

Description: A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

Measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for grand glass opacities

Time: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

Description: A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

Measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for consolidation

Time: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

Description: A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

Measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for total lesions

Time: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

Measure: Requirement for low flow oxygen therapy during the initial hospitalisation: yes/no

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Requirement for high flow oxygen therapy during the initial hospitalisation: yes/no

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Requirement for non-invasive ventilation during the initial hospitalisation: yes/no

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Requirement for invasive ventilation during the initial hospitalisation: yes/no

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Requirement for dialysis during the initial hospitalisation: yes/no

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Requirement for extracorporeal membrane oxygenation during the initial hospitalisation: yes/no

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Classification of acute respiratory distress syndrome (ARDS) according to the Berlin criteria during initial hospitalization: absent, mild, moderate or severe

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Length of stay (hours) in intensive care

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Length of stay (hours) in hospital

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Days alive and without low flow oxygen therapy

Time: Day 28

Measure: Days alive and without high flow oxygen therapy

Time: Day 28

Measure: Days alive and without any oxygen therapy

Time: Day 28

Measure: Days alive and without non-invasive ventilation

Time: Day 28

Measure: Days alive and without invasive ventilation

Time: Day 28

Measure: Days alive and without extracorporeal membrane oxygenation

Time: Day 28

Measure: Days alive and without intensive care

Time: Day 28

Measure: Days alive and without hospitalisation

Time: Day 28

Measure: Mortality

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Mortality

Time: Day 28

Measure: Club cell secrectory protein polymorphism A38G

Time: Between day 0 and day 28

Other Outcomes

Measure: Presence/absence of incident hyperglycemia during hospitalization

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Presence/absence of secondary infection during hospitalization

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Presence/absence of cardiovascular event (ischemic, stroke, other) during hospitalization

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Presence/absence of digestive hemorrhage during hospitalization

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Presence/absence of neuro-psychiatric event (acute delirium, depressive syndrome, decompensation of an underlying psychiatric pathology) during hospitalization

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Adverse events

Time: Day of hospital discharge (expected maximum of 28 days)

Measure: Adverse events

Time: Day 28
345 Efficacy of Treatment With Vitamin D in Patients Diagnosed With COVID-19 Who Presenting Vitamin D Deficiency and Pneumonia.

HYPOTHESIS: The administration of vitamin D supplements to patients who have a positive diagnosis for SARS-Cov-2, acute pneumonia requiring hospital admission and vitamin D deficiency have a more favourable evolution than subjects not treated with vitamin D (placebo). This favourable evolution will translate into a reduction in mortality, fewer ICU admissions and fewer days of stay in hospital. OBJECTIVES: PRINCIPAL: To assess whether the group of patients receiving vitamin D supplements have a less severe evolution of their acute pneumonia, translated into lower mortality, than patients who do not receive that supplement. SECONDARY: 1) To determine the number of intensive care admissions and the number of days of admission in both groups (control group and intervention group). 2) To estimate the prevalence of Vitamin D deficiency in the patients studied and the effectiveness of its supplementation. 3) To establish the degree of complexity of each study group and carry out a cost-effectiveness study. METHODOLOGY: DESIGN: Clinical trial, randomized, placebo-controlled and double-blind, with two parallel groups The active treatment will be vitamin D (Hydroferol soft capsules of 0.266 mg). The placebo will consist of a tablet with the same external characteristics and with the same treatment scheme but which will not contain any vitamin D active ingredients.

NCT04621058
Conditions
  1. SAR
  2. SARS Pneumonia
Interventions
  1. Drug: Vitamin D
  2. Drug: PLACEBO
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Mortality reduction

Measure: MORTALITY

Time: At 21 days.

Secondary Outcomes

Description: Intensive care admissions reduction

Measure: Intensive care admissions

Time: At 21 days

Description: Length of hospital stay reduction

Measure: Length of hospital stay

Time: AT 21 DAYS

Description: To assess the prevalence of vitamin D deficiency at baseline

Measure: Prevalence of vitamin D deficiency

Time: At baseline

Description: To calculate the incremental cost per event (mortality) avoided

Measure: Incremental cost effectiveness ratio (ICER)

Time: At 21 days
346 Studio in Aperto Sulla Somministrazione di Plasma di Paziente Convalescente da COVID- 19 a Paziente Con Polmonite COVID-19 Ospedalizzato, Non in Terapia Intensiva

Aim of the study is to verify the efficacy and safety of convalescent hyperimmune plasma infusion in hospitalized covid-19 patients non in ITU with pneumonia and respiratory symptoms within seven days from the beginning of symptoms. Efficacy is evaluated by the number of patients who will improve their clinical condition and will not be admitted to ITU. .Safety is considered in relation to adverse reactions to plasma infusion.

NCT04622826
Conditions
  1. Covid-19 Pneumonia
Interventions
  1. Biological: immune plasma
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: number of patients admitted to ITU after immune plasma transfusion

Measure: ITU admission

Time: up to 30 days

Description: O2 support will be monitored and reported in its various modes of administration (e.g. nasal cannula, high flow nasal cannula, noninvasive ventilation, mechanical ventilation)

Measure: administration of O2

Time: up to 30 days

Description: number of subject deaths

Measure: hospital mortality

Time: up to 90 days

Description: number of participants with treatment-related adverse events as assessed by CTCAE v4.0"

Measure: immune plasma infusion adverse reaction

Time: in the first 24-48 hours
347 An Open-label, Randomized, Multicenter, Controlled Clinical Trial to Evaluate the Efficacy and Safety of CKD-314 (Nafabelltan) in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia

The primary objective of this study is to evaluate the efficacy of CKD-314 (Nafabelltan) compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale in hospitalized adult patients diagnosed with COVID-19 pneumonia

NCT04623021
Conditions
  1. COVID-19
Interventions
  1. Drug: Nafamostat Mesilate
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time to clinical improvement (TTCI) was defined as time (days) from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first

Measure: Time to clinical improvement

Time: up to 28 days

Secondary Outcomes

Description: Day of recovery is defined as the first day on which the subject satisfies one of the following: 1) Not hospitalized with resumption of normal activities; 2) Not hospitalized, but unable to resume normal activities; 3) Hospitalization, not requiring supplemental oxygen- no longer required ongoing medical care

Measure: Time to recovery

Time: up to 28 days

Measure: Proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status

Time: Day 4, 7, 11, 14 and 28

Description: 1) Not hospitalized with resumption of normal activities; 2) Not hospitalized, but unable to resume normal activities; 3) Hospitalization, not requiring supplemental oxygen- no longer required ongoing medical care

Measure: Proportion of patients with recovery as defined as the subject satisfies one of the following

Time: Day 4, 7, 11, 14 and 28

Measure: Change of clinical status assessed by 7-category ordinal scale

Time: Day 4, 7, 11, 14 and 28

Measure: Change in National Early Warning Score (NEWS)

Time: Day 4, 7, 11, 14 and 28

Measure: Time to National Early Warning Score (NEWS) of ≤ 2 which is maintained for 24 hours

Time: up to 28 days

Description: Measured as proportion of patients with improved, not changed or worsened CT scan/X-ray

Measure: Changes on CT scan/X-ray

Time: Day 5, 11, 14 and 28

Measure: Change from baseline of CRP

Time: Day 4, 7, 11, 14 and 28

Description: Decrease to the level of <10 mg/l

Measure: Time to normalize the CRP

Time: up to 28 days

Measure: Duration of hospitalization

Time: up to 28 days

Measure: Duration of non-invasive ventilation or high flow oxygen use

Time: up to 28 days

Description: Proportion of patients of non-invasive ventilation or high flow oxygen use

Measure: Incidence of non-invasive ventilation or high flow oxygen use

Time: up to 28 days

Measure: Duration of supplement oxygen use

Time: up to 28 days

Description: Proportion of patients of supplement oxygen use

Measure: Incidence of supplement oxygen use

Time: up to 28 days

Measure: Duration of invasive ventilation or extracorporeal membrane oxygenation (ECMO) use

Time: up to 28 days

Description: Proportion of patients of invasive ventilation or extracorporeal membrane oxygenation (ECMO) use

Measure: Incidence of invasive ventilation or extracorporeal membrane oxygenation (ECMO) use

Time: up to 28 days

Measure: 28-Day mortality

Time: up to 28 days
348 Pilot Study on Peripheral Vascular Function in Covid-19 Patient

The 2019 coronavirus-induced infection (COVID-19) has caused a pandemic that has spread worldwide. Up to date, many subjects affected by the virus report important sequelae on different organs increasing morbidity and exacerbating previous pathological conditions. Mortality is also increased in cases of comorbidities such as cardiovascular disease, hypertension and diabetes. COVID-19 infection is caused by Coronavirus-2 (SARS-CoV-2). Concerning the specific interaction of SARS-CoV-2 with the cardiovascular system, we know that this virus enters the body through the receptors for the conversion of angiotensin II (ACE2r) that are present in the lungs, heart, intestinal epithelium and vascular endothelium. This receptor's availability suggests a multi-organ involvement with a consequent multi-organ dysfunction, as found in patients affected by SARS-CoV-2 infection. Furthermore, poor vascular peripheral function -usually correlated with old age and long periods of bed rest or hypomobility- is a distinguishing characteristic of the population affected by COVID-19, as well. Thus, it is reasonable to expect that peripheral vascular function, already deteriorated by aging and common age-related diseases, can be further compromised by COVID-19 and by the forced hypomobility, typically experienced during the acute phase of the disease. The main aim of this project will be to investigate the peripheral NO-mediated vascular function in the leg of patients recovering from Covid-19 pneumonia. A significant vascular dysfunction is expected to be found in post COVID individuals and to be correlated to the relevant clinical variables.

NCT04625036
Conditions
  1. COVID-19 Pneumonia
Interventions
  1. Diagnostic Test: Single passive leg movement
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Leg Blood Flow will be analyzed with an ultrasound examination using the Single Passive Leg Movement technique. In particular, the investigation consists of an ultrasound performed on the common femoral artery using Doppler method with a linear probe with a frequency of 5 MHz. The subject will be placed in a sitting position at rest for 20 minutes before the test is performed. The protocol consists of image acquisition for 60 seconds (basal measurement), followed by a passive flexion-extension of the knee performed by health care personnel at a rate of 1 Hz. At the end of the movement, the recording will continue for another 60 seconds.

Measure: Leg Blood Flow

Time: Baseline

Secondary Outcomes

Description: Routinary measures as single anthropometric data: height (cm) and weight (Kg) and aggregate measure as body mass index (Kg/m2)

Measure: Clinical evaluations

Time: Baseline

Description: Clinical course of disease (days) will be noted for all subjects

Measure: Clinical characteristics

Time: Baseline

Description: Ventilatory support (yes or no) will be noted for all subjects

Measure: Presence of device

Time: Baseline

Description: Drug therapy (list of drugs) will be noted for all subjects

Measure: Therapy

Time: Baseline

Description: Number of comorbidities will be noted for all subjects

Measure: Clinical characteristics

Time: Baseline

Description: All subjects will perform blood tests to investigate bio-humoral data. Normal values: <125 pg/mL

Measure: Biochemical evaluations - ProBNP

Time: Baseline

Description: All subjects will perform blood tests to investigate bio-humoral data. Normal values:<500 ng/mL FEU

Measure: Biochemical evaluations - D-dimer

Time: Baseline

Description: All subjects will perform blood tests to investigate bio-humoral data. Normal values:<=5.00 mg/L

Measure: Biochemical evaluations - PCR

Time: Baseline

Description: Therapists ask the participants to sit down on a chair without armrests. The assisted use of the arms is not allowed during the STS test. The therapists instruct the participants to complete as many sit-to-stand cycles as possible within 60 s at self-paced speed and count the number of fully-completed STS cycles. Normal values: 50/min-27/min.

Measure: Functional evaluations - 1-Minute Sit To Stand

Time: Baseline

Description: The 6MWT is a self-paced test of walking capacity. Patients will be asked to walk as far as possible in 6 min along a flat corridor. The distance in metres is recorded. Standardised instructions and encouragement are given during the test. Predicted 6MW Distance follows this calculation: 361-(age in yrs x 4) + (height in cm x 2) + (HRmax/HRmax % pred x 3) - (weight in kg x 1.5) - 30 (if females).

Measure: Functional evaluations - 6-Minute Walking Test

Time: Baseline

Description: The patient will be seated with the elbow flexed 90" and forearm supinated; the dynamometer will be positioned just proximal to styloid processes and the patient will be asked to flex his elbow. Prediction equation=229.421-84.836*(0=male, 1=female) +0,165*weight-1.503*age.

Measure: Functional evaluations - Biceps' muscle strength with dynamometer

Time: Baseline

Description: The patients will be seated with hips and knees flexed 90''; the dynamometer will be positioned just proximal to malleoli and the patient will be asked to extend his knee. Prediction equation=358.455-87.581*(0=male, 1=female) +0.297*weight-3.136*age

Measure: Functional evaluations - Quadriceps' muscle strength with dynamometer

Time: Baseline
349 Hydroxychloroquine for the Treatment of SARS-CoV2 (COVID 19) in the Critically Ill Patient: Pharmacokinetic Study. (CHLORO-VID)

This study is a prospective, observational, open, monocentric multisite, pharmacokinetic study of hydroxychloroquine in critically ill patients. The aim of this study is to assess the pharmacokinetic behavior of hydroxychloroquine in COVID-19 critically ill patients treated with crushed hydroxychloroquine tablets (administered enterally using a nasogastric tube).

NCT04625218
Conditions
  1. COVID-19 Pneumonia
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: residual plasma concentration measured before re-administration of the treatment

Measure: residual plasma concentration

Time: Day 3

Description: residual plasma concentration measured before re-administration of the treatment

Measure: residual plasma concentration

Time: Day 5

Description: residual plasma concentration measured before re-administration of the treatment

Measure: residual plasma concentration

Time: Day 7

Description: residual plasma concentration measured before re-administration of the treatment

Measure: residual plasma concentration

Time: Day 9

Secondary Outcomes

Description: number of days without artificial ventilation

Measure: The number of days without artificial ventilation

Time: Day 28

Description: The length of hospital stay in intensive care measured in days number

Measure: The length of hospital stay in intensive care

Time: Day 28

Description: Statu alive or death

Measure: Survival

Time: Day 28

Description: Viral replication on Day 7 measured by biological analysis of the bronchoalveolar lavage fluid

Measure: Viral replication in the control bronchoalveolar lavage fluid on Day 7

Time: Day 7

Description: Viral replication on Day 14 measured by biological analysis of the bronchoalveolar lavage fluid

Measure: Viral replication in the control bronchoalveolar lavage fluid on Day 14

Time: Day 14
350 Epidemiological and Clinical Characteristics of COVID-19 Patients in Kazakhstan in Early 2020: a Retrospective, Observational Cohort Study

The aim of this study is to assess the epidemiological and clinical features of patients diagnosed with COVID-19 in Kazakhstan at the onset of the pandemic.

NCT04627194
Conditions
  1. Covid19
  2. Pneumonia, Viral
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Risk factors associated with disease severity and their odds ratios (ORs) will be assessed by the univariable and multivariable logistic regression models.

Measure: Clinical and demographic predictors of disease severity among hospitalized COVID-19 patients.

Time: approximately 70 days

Description: Risk factors associated with death and their odds ratios (ORs) will be assessed by the univariable and multivariable logistic regression models.

Measure: Clinical and demographic predictors of mortality among hospitalized COVID-19 patients.

Time: approximately 70 days
351 Double-Blind, Randomized, Placebo-Controlled, Adaptive Design, Multi-Center Phase 3 Study to Evaluate the Efficacy and Safety of Fostamatinib in COVID-19 Subjects

The study is a double-blind, randomized, placebo-controlled, adaptive design, multi-center, Phase 3 study to evaluate the efficacy and safety of fostamatinib in COVID-19 subjects.

NCT04629703
Conditions
  1. Covid19
  2. SARS (Severe Acute Respiratory Syndrome)
  3. SARS Pneumonia
  4. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
  5. Pneumonia
  6. Pneumonia, Viral
Interventions
  1. Drug: Fostamatinib
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Progression to severe/critical disease within 29 days of first dose of study treatment

Measure: Progression to severe/critical disease within 29 days of first dose of study treatment

Time: 29 days

Secondary Outcomes

Description: Proportion of subjects transferred into the intensive care unit (ICU) or who died prior to Day 29

Measure: Proportion of subjects transferred into the intensive care unit (ICU) or who died prior to Day 29

Time: 29 days

Description: Total number of calendar days hospitalized through Day 29

Measure: Total number of calendar days hospitalized through Day 29

Time: 29 days
352 Expanded Access Study of Phage Treatment in Covid-19 Patients on Anti-Microbials for Pneumonia or Bacteremia/Septicemia Due to A. Baumannii, P. Aeruginosa or S. Aureus

Bacteriophage treatment in Covid-19 patients being treated with Anti-Microbials for Pneumonia or Bacteremia/Septicemia.

NCT04636554
Conditions
  1. Covid19
  2. Bacteremia
  3. Septicemia
  4. Acinetobacter Baumannii Infection
  5. Pseudomonas Aeruginosa Infection
  6. Staph Aureus Infection
Interventions
  1. Other: Phage Therapy
MeSH:Infection Communicable Diseases Bacteremia Pseudomonas Infections Sepsis Toxemia Pneumonia
HPO:Pneumonia Sepsis

353 Randomized Controlled Trial of Methylprednisolone Versus Dexamethasone in COVID-19 Pneumonia (MEDEAS Trial)

Low-dose glucocorticoid treatment is the only intervention shown to significantly reduce mortality in cases of COVID-19 pneumonia requiring oxygen supplementation or ventilatory support. In particular, a large UK randomized controlled trial (RECOVERY trial) demonstrated the efficacy of dexamethasone at a dosage of 6mg/day for 10 days in reducing mortality compared to usual therapy, with a greater impact on patients requiring mechanical ventilation (36% reduction) or oxygen therapy (18% reduction) than on those who did not need respiratory support (doi: 10.1056/NEJMoa2021436). However, there is still paucity of information guiding glucocorticoid administration in severe pneumonia/ARDS and no evidence of the superiority of a steroid drug -nor of a therapeutic scheme- compared to the others, which led to a great heterogeneity of treatment protocols and misinterpretation of available findings. In a recent longitudinal observational study conducted in Italian respiratory high-dependency units, a protocol with prolonged low-dose methylprednisolone demonstrated a 71% reduction in mortality and the achievement of other secondary endpoints such as an increase in ventilation-free days by study day 28 in a subgroup of patients with severe pneumonia and high levels of systemic inflammation (doi: 10.1093/ofid/ofaa421). The treatment was well tolerated and did not affect viral shedding from the airways. In light of these data, the present study aims to compare the efficacy of a methylprednisolone protocol and that of a dexamethasone protocol based on previous evidence in increasing survival by day 28, as well as in reducing the need and duration for mechanical ventilation, among hospitalized patients requiring noninvasive respiratory support (oxygen supplementation and/or noninvasive ventilation).

NCT04636671
Conditions
  1. Covid19
  2. Viral Pneumonia Human Coronavirus
  3. Severe Acute Respiratory Syndrome
Interventions
  1. Drug: Methylprednisolone
  2. Drug: Dexamethasone
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Survival proportion at 28 days in both arms

Measure: Survival

Time: 28 days

Secondary Outcomes

Description: Number of days free from mechanical ventilation (either noninvasive or invasive) by study day 28 in both arms

Measure: Reduction in the need for mechanical ventilation

Time: 28 days

Description: Number of days of hospitalization for patients discharged alive in both arms

Measure: Length of hospitalization

Time: From date of randomization until the date of hospital discharge, assessed up to 60 days

Description: Proportion of patients requiring tracheostomy in both arms

Measure: Need for tracheostomy

Time: Day 28

Description: C-reactive protein level (mg/L) at study day 3, 7 and 14 in both arms

Measure: Reduction in systemic inflammation markers

Time: Day 3, 7 and 14

Description: PaO2/FiO2 ratio (mmHg) at study day 3, 7 and 14 in both arms

Measure: Amelioration of oxygenation

Time: Day 3, 7 and 14

Description: WHO clinical progression scale at study day 3, 7 and 14 in both arms

Measure: Disease progression

Time: Day 3, 7 and 14
354 Effectiveness of Pulmonary Rehabilitation Program in Patients With SARS-CoV-2 Pneumonia

The aim of the study is to investigate the efficacy of pulmonary rehabilitation (PR) program to patients with Sars-CoV-2 pneumonia in the post-acute period on pulmonary functions, exercise capacity and anxiety level. 100 patients diagnosed with Sars-CoV-2 pneumonia will be enrolled in this prospective, interventional study according to inclusion/exclusion criteria. Patients will be evaluated and a personalized PR program will be organized before hospital discharge. After discharge, the pulmonary rehabilitation program will continue in telerehabilitation. In the telerehabilitation program, exercises will be supervised by a physiotherapist two days a week, and patients will be asked to do the exercises themselves for the other 3 days. Patients will also receive exercise videos for these 3 days. Patients will be followed for 4 weeks and will be called for final evaluation

NCT04642040
Conditions
  1. Covid19
  2. Covid19 Pneumonia
  3. SARS-CoV 2 Pneumonia
Interventions
  1. Other: Pulmonary Rehabilitation
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The mMRC scale is a self-rating tool to measure the degree of disability that breathlessness poses on day-to-day activities on a scale from 0 to 4. 0: no breathlessness except on strenuous exercise; 4: too breathless to leave the house, or breathless when dressing or undressing.

Measure: Change in Dyspnea level as measured by modified Medical Research Council (mMRC) Dyspnea Scale

Time: 4 weeks

Description: 30 sec- STS determines lower extremity strength and physical fitness in older adults. The number of repetitions is recorded.

Measure: Change in functional capacity as measured by 30-second sit-to-stand test

Time: 4 weeks

Secondary Outcomes

Description: IPAQ-Short Form is used to measure level of physical activity.It consists of 7 questions that provide information about time spent on walking, moderate to vigorous physical activities, and time spent sitting. The energy required for the activities was calculated by the MET-minute/week score. Standard MET values for these activities are: Walking = 3,3 METS; Moderate Physical Activity = 4,0 METS; Vigorous Physical Activity = 8.0 METS; Sitting = 1,5 METS

Measure: Change in physical activity level as measured by International Physical Activity Questionnaire (IPAQ) -Short Form

Time: 4 weeks

Description: HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression.The total scores range is 0-21 for both depression and anxiety scores. A higher score indicates a worse depression and anxiety.

Measure: Change in anxiety and depression as measured by Hospital Anxiety and Depression Scale (HADS)

Time: 4 weeks
355 Mortality in Patients With Severe SARS-CoV-2 Pneumonia Who Underwent Tracheostomy Due to Prolonged Mechanical Ventilation

Background: Invasive mechanical ventilation (IMV) in COVID-19 patients has been associated with a high mortality rate. In this context, the utility of tracheostomy has been questioned in this group of ill patients. This study aims to compare in-hospital mortality in COVID-19 patients with and without tracheostomy due to prolonged IMV Methods: Cohort study of adult COVID-19 patients subjected to prolonged IMV. Since the first COVID-19 case (March 3, 2020) up to November 30, 2020, all adult critical patients supported with IMV by 10 days or more at the Hospital Clínico Universidad de Chile will be included in the cohort. Pregnant women and non-adult patients will be excluded. Baseline characteristics, comorbidities, laboratory data, disease severity, and ventilatory support will be retrospectively collected from clinical records. The indication of tracheostomy, as part of our standard of care, will be indicated by a team of specialists in intensive care medicine, following national guidelines, and consented to by the patient's family. The 90-days mortality rate will be the primary outcome, whereas IMV days, hospital/CU length of stay, and the frequency of healthcare-associated infections will be the secondary outcomes. Also, a follow-up interview will be performed one year after a hospital discharged in order to assess the vital status and quality of life. The mortality of patients subjected to tracheostomy will be compared with the group of patients without tracheostomy by logistic regression models. Furthermore, propensity-score methods will be performed as a complementary analysis.

NCT04642703
Conditions
  1. Mechanical Ventilation
  2. Covid19
  3. Tracheostomy
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Death occurred during the follow-up

Measure: 90-days mortality rate

Time: Since mechanical ventilation onset to death or 90-days follow-up

Secondary Outcomes

Description: Days from hospital admission to discharge

Measure: Hospital length of stay

Time: From hospital admission to discharge, up to 90 days

Description: Days elapsed in the first ICU admission

Measure: ICU length of stay

Time: From first ICU admission to transfer at a lower complexity unit, up to 90 days

Description: Days of invasive ventilatory support

Measure: Time of mechanical ventilation

Time: From orotracheal intubation to mechanical ventilation extubation (weaning), up to 90 days

Description: Frequency of respiratory, urinary tract, blood stream and invasive device-related infections

Measure: Health-care associated infections

Time: From hospital admission to discharge, up to 90 days

Description: Score on the the Short Form-36 Health Survey (SF-36). SF-36 is a 36-item questionary that assesses the quality of life on eight health-related aspects. It scores from 0 (maximum disability) to 100 (no disability): the lower the score the more disability.

Measure: Long-term quality of life assessed by Short Form-36 Health Survey, SF-36

Time: One year after hospital discharge
356 Efficacy of Anakinra in the Management of Patients With COVID-19 Infection in Qatar: A Randomized Clinical Trial

Coronavirus Disease 2019 (COVID-19) was first isolated in Wuhan, China in December 2019. It is rapidly spreading worldwide, posing a severe threat to global health. Many therapeutics have been investigated for the treatment of this disease with inconclusive outcomes. Anakinra - an interleukin (IL)-1 receptor antagonist - had showed survival benefits in patients with macrophage activation syndrome (MAS) and sepsis and was investigated for the use in COVID-19 infection with promising outcomes.

NCT04643678
Conditions
  1. Covid19
  2. Pneumonia
  3. Cytokine Release Syndrome
  4. Corona Virus Infection
  5. Viral Infection
Interventions
  1. Drug: Anakinra
  2. Other: Standard of Care
MeSH:Infection Communicable Diseases Virus Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Defined as WHO Clinical Progression score of <6 [patient alive, not requiring invasive, non-invasive, or high flow oxygen therapy, vasopressors, dialysis or Extracorporeal membrane oxygenation (ECMO)].

Measure: Treatment Success at day 14

Time: Day 14

Secondary Outcomes

Description: Change in WHO Clinical Progression Score between day 1 and day 7 [WHO Clinical Progression score: 0 (Uninfected) - 10 (Dead)]

Measure: Change in WHO Clinical Progression Score

Time: Day 7

Description: Time to ICU admission up to 28 days

Measure: Time to ICU admission

Time: Day 28

Description: Incidence of adverse events up to 28 days

Measure: Incidence of Adverse Events

Time: Day 28

Description: Length of hospital stay up to 28 days

Measure: Length of hospital stay

Time: Day 28

Description: All-cause mortality rate at hospital discharge or at 28 days, whichever is first

Measure: All-cause Mortality

Time: Day 28
357 Circulatory and Endothelial Coherence in COVID-19 and Non-COVID-19 Patients With Sepsis - Prospective, Observational Pilot Study

This prospective observational pilot study investigates circulatory coherence in patients with COVID and non-COVID sepsis by comparison of microcirculation, endothelial glycocalyx, and clinical course

NCT04644302
Conditions
  1. Viral Pneumonia
  2. Sepsis
Interventions
  1. Diagnostic Test: microcirculation recording
MeSH:Sepsis Toxemia Pneumonia, Viral Pneumonia
HPO:Pneumonia Sepsis

Primary Outcomes

Description: PPV describes microcirculation dysfunction

Measure: change in Proportion of Perfused Vessels (PPV) parameter

Time: 1st, 2nd and 3rd day

Description: Syndecan-1 is a marker of endothelial glycocalyx

Measure: change in Syndecan-1 serum concentration

Time: 1st, 2nd and 3rd day

Secondary Outcomes

Description: albuminuria is a marker of glomerular endothelial cells dysfunction

Measure: change in albuminuria

Time: 1st, 2nd and 3rd day

Description: mortality in 28 days from ICU admission

Measure: mortality in 28 days

Time: 30 days
358 Efficacy of Fuzheng Huayu Tablets for Treating Pulmonary Inflammation in Patients With COVID-19: A Case-Control Study

The 2019 novel coronavirus (2019-nCoV) infection caused clusters of severe respiratory illness similar to SARS and was associated with ICU admission and high mortality. There is no confirmed antivirus therapy for people infected 2019-nCoV, most of them should receive supportive care to help relieve symptoms. This clinical trial is to evaluate the effect of Fuzheng Huayu tablet on lung inflammation in intensive patients with novel coronavirus pneumonia and reduce the progressive rate to critical type.

NCT04645407
Conditions
  1. Novel Coronavirus Pneumonia
Interventions
  1. Drug: Fuzheng Huayu tablet
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of the therapeutic effect of Fuzheng huayu tablet

Measure: the percentage of patients showing improvement in chest CT

Time: Week 2

Secondary Outcomes

Description: Evaluation of pulmonary inflammation improvement

Measure: remission rate or progression rate of critical illness

Time: Week 2

Description: Evaluation of pulmonary inflammation improvement

Measure: clinical remission rate of respiratory symptoms

Time: week 2

Description: Evaluation of pulmonary inflammation improvement

Measure: routine blood examination

Time: Week 2

Description: Evaluation of the therapeutic effect of Fuzheng huayu tablet

Measure: C-reactive protein level

Time: Week 2

Description: Evaluation of pulmonary inflammation improvement

Measure: procalcitonin level

Time: Week 2

Description: Evaluation of pulmonary inflammation improvement

Measure: oxygen saturation

Time: Week 2
359 Clinical Outcome of Patients With COVID-19 Pneumonia Treated With Corticosteroids and Colchicine in Colombia

Cross sectional study of 301 adult patients with Covid-19 Pneumonia treated with corticosteroid and/or colchicine

NCT04654416
Conditions
  1. Covid-19
Interventions
  1. Drug: Corticosteroid with or without colchicine
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Dead or alive

Measure: Outcome

Time: March 20 to August 07, 2020
360 A Single-Blind Dose-Ranging Pharmacodynamic Study of Auxora for the Treatment of Patients With Critical COVID-19 Pneumonia

This is a single-blind study consisting of up to 3 cohorts Patients will be randomized 3:1 to Auxora or Placebo. The first 4 patients will be enrolled in Cohort 1. If dose escalation occurs, the next 8 patients will be enrolled in Cohort 2 If dose escalation occurs, the next 8 patients will be enrolled in Cohort 3. The decision to escalate dosing will be made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.

NCT04661540
Conditions
  1. Pneumonia
Interventions
  1. Drug: CM4620-IE (Injectable Emulsion)
  2. Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Decrease in interferon-gamma producing T-cells in Broncoalveolar lavage (BAL) fluid

Time: Baseline Assessment up to 120 hours

Secondary Outcomes

Measure: Number of Days in the Hospital after randomization

Time: From randomization until discharge from the hospital assessed up to 30 days

Measure: Number of Days in the Intensive Care Unit (ICU) after randomization

Time: From randomization until discharge from ICU assessed up to 30 days

Measure: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time: From randomization up to 30 days

Measure: Intensity and relationship of TEAEs and SAEs

Time: From randomization up to 30 days

Description: Changes in cardiac conduction are defined as: QTcF interval of ≥ 500 msec; QTcF prolongation of ≥ 60 msec as compared to baseline; Mobitz Type II second degree atrioventricular (AV) block; Third degree or high grade AV block; or Polymorphic Ventricular Tachycardia

Measure: Pre-defined changes in cardiac conduction assessed by ECG

Time: From screening up to 144 hours

Measure: Mortality

Time: Randomization up to 30 days

Description: Concentration of Auxora from blood samples and fluid collected from BAL

Measure: Plasma Levels of CM4620

Time: From end of first infusion of study drug up to 144 hours
361 Efficacy and Safety of High-dose Vitamin C Combined With Traditional Chinese Medicine in the Treatment of Moderate and Severe Coronavirus Pneumonia (COVID-19)

In December 2019, coronavirus pneumonia (COVID-19) was detected in many cases in Wuhan, China. With the rapid spread of the coronavirus, cases of COVID-19 were also reported in other cities of China and other countries. COVID-19 can cause amplification of the pulmonary inflammatory responses, including the production of a large amount of free radicals and the release of inflammatory factors, in a short time after infection, leading to lung tissue damage and dysfunction, even resulting in life-threatening respiratory distress syndrome and respiratory failure. At present, there are no effective drugs targeting COVID-19. Previous studies have shown that Buzhong Yiqi Decoction has anti-bacterial, anti-viral, and anti-allergy effects. High-dose vitamin C also has anti-oxidative and anti-toxin effects, possibly exhibiting good effects in the treatment of viral infection and critical respiratory diseases. The study objectives include (1) investigate whether Buzhong Yiqi Decoction can improve the clinical symptoms of patients with mild and severe COVID-19 and accelerate recovery and to further investigate the clinical efficacy of high-dose vitamin C combined with traditional Chinese medicine in the treatment of mild and severe COVID-19; (2) to assess the safety of high-dose vitamin C combined with Chinese medicine in the treatment of mild and severe COVID-19.

NCT04664010
Conditions
  1. COVID-19
Interventions
  1. Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C
  2. Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose
  3. Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The discharge criteria of Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) are applied: a) body temperature is back to normal for more than three days; b) respiratory symptoms improve obviously; c) pulmonary imaging shows obvious resolution of inflammation; d) nuclei acid tests negative twice consecutively on respiratory tract samples such as sputum and nasopharyngeal swabs (sampling interval being at least 24 hours)

Measure: Recovery time

Time: From date of randomization until the date of discharge, assessed up to 6 months

Secondary Outcomes

Description: Time of disappearance of fever in degrees centigrade

Measure: Time of disappearance of fever symptoms

Time: From date of randomization until the date of discharge, assessed up to 6 months

Description: The rate of conversion from COVID-19 positive to COVID-19 negative

Measure: The rate of conversion from COVID-19 positive to COVID-19 negative

Time: From date of randomization until the date of discharge, assessed up to 6 months.

Description: Time of disappearance of cough in times per day

Measure: Time of disappearance of cough

Time: From date of randomization until the date of discharge, assessed up to 6 months

Description: Respiratory rate in times/minute with blood gas analysis

Measure: Respiratory rate

Time: 1-14 days after treatment

Description: Blood oxygen saturation in percent with blood gas analysis

Measure: Blood oxygen saturation

Time: 1-14 days after treatment

Description: PaO2 in kPa with blood gas analysis

Measure: PaO2

Time: 1-14 days after treatment

Description: PaCO2 in kPa with blood gas analysis

Measure: PaCO2

Time: 1-14 days after treatment

Description: The time in days of patients of obvious improvement as shown on chest CT scans relative to admission

Measure: The time of obvious improvement as shown on chest CT scans relative to admission

Time: From date of randomization until the date of discharge, assessed up to 6 months

Description: The rate in percentages of patients of obvious improvement as shown on chest CT scans relative to admission

Measure: The rate of obvious improvement as shown on chest CT scans relative to admission

Time: From date of randomization until the date of discharge, assessed up to 6 months

Description: Levels of C-reactive protein measurement in mg/L

Measure: Levels of C-reactive protein

Time: 1-14 days after treatment

Description: Erythrocyte sedimentation rate in mm/h

Measure: Erythrocyte sedimentation rate

Time: 1-14 days after treatment

Description: Levels of Procalcitonin in ng/mL

Measure: Levels of Procalcitonin

Time: 1-14 days after treatment

Description: Serum Levels of interleukin-6 in ng/L

Measure: Levels of interleukin-6

Time: 1-14 days after treatment

Description: Levels of interleukin-10 in ng/L

Measure: Levels of interleukin-10

Time: 1-14 days after treatment

Description: Levels of tumor necrosis factor-alpha in ng/mL

Measure: Levels of tumor necrosis factor-alpha

Time: 1-14 days after treatment

Other Outcomes

Description: Ultrasound examination of the kidney, ureter, and bladder after treatment to mainly check for urolithiasis

Measure: Ultrasound examination of the urinary system

Time: 1-14 days after treatment
362 Expert Statements on Infection Control in Intensive Care Unit for Severe Acute Respiratory Syndrome Coronavirus 2

The investigators aim to develop expert consensus statements on infection control management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in intensive care units (ICU).

NCT04665960
Conditions
  1. Covid19
  2. SARS-CoV Infection
  3. SARS Pneumonia
  4. Coronavirus Infection
  5. Infection
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Survey questionnaire with seven point Likert scale (1-3 means disagreement and 5-7 means agreement) and multiple choice statements

Measure: Consensus using participating experts opinions.

Time: 30 days
363 A Randomized, Multicentre, Double-blind Study to Evaluate the Efficacy of High-dose Administration of Methylprednisolone in Addition to Standard Treatment, in SARS-CoV2 (COVID-19) Pneumonia Patients

This double blind, randomized study is aiming to evaluate the efficacy of three doses (1gr/day) of methylpredisolone added to standard therapy in patients, with documented COVID-19 pneumonia, requiring hospitalization but not mechanical ventilation.

NCT04673162
Conditions
  1. Covid19
Interventions
  1. Drug: Methylprednisolone, Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: the interval between randomization and discharge from the hospital without the need for supplemental oxygen

Measure: Length of hospitalization

Time: 30 days since randomisation
364 Utility of Empiric Antibiotics on Admission for Non-intubated Patients With Novel Coronavirus Diseases 2019 (COVID-19): A Retrospective Cohort Study of Electronic Health Records

This retrospective analysis of inpatient data obtained from administrative and electronic medical records will investigate the role of empiric antibiotics on admission on the mortality for non-intubated patients presenting with Novel Coronavirus Diseases 2019 (COVID-19) associated pneumonia without extra-pulmonary sources of infection or septic shock.

NCT04674410
Conditions
  1. Covid19
  2. Coronavirus Infection
  3. Pneumonia
Interventions
  1. Drug: Antibiotic
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Death during the hospitalization or discharge to hospice

Measure: In-Hospital Mortality or discharge to hospice

Time: From time of admission to death during the hospitalization or discharge to hospice

Secondary Outcomes

Description: Mechanical ventilation initiated after 48 hours into the admission as a marker of clinical deterioration and its relationship to receipt of empiric antibiotic

Measure: Rates of Mechanical Ventilation

Time: From 48 hours post admission to discharge or death

Description: Identify the risk of C. difficile infection on patients according to empiric therapy status as captured by diagnosis codes not present-on-admission

Measure: Rates of C. difficile infection

Time: not present-on-admission

Description: As a marker of morbidity and and its relationship to receipt of empiric antibiotic therapy

Measure: Length of stay for survivors

Time: From admission to discharge (not to hospice)

Description: As a marker of clinical deterioration and its relationship to receipt of empiric antibiotic therapy among patients who did not require ICU admission upon arrival

Measure: Rates of ICU Admission

Time: From 48 hours post admission to discharge

Description: Identify the risk of acute kidney injury according to empiric therapy status as captured by diagnosis codes not present-on-admission

Measure: Rates of Acute Kidney Injury

Time: not present-on-admission

Description: For patients in hospital for at least 5 days

Measure: Days free of antibiotics

Time: 5 days from admission to discharge or primary outcome

Description: As above, as captured by diagnosis codes not present-on-admission

Measure: Rates of secondary infections due to antibiotic resistant pathogens

Time: not present-on-admission
365 A Randomized, Open-Label Study of the Efficacy and Safety of Aralast NP, an Alpha-1 Antitrypsin Infusion Therapy With Antiviral Treatment and Standard of Care Versus Antiviral Treatment With Standard of Care in Hospitalized Patients With Pneumonia and COVID-19 Infection

This is a Randomized, Open-Label Study of the Efficacy and Safety of Aralast NP Infusion Therapy with Antiviral Treatment and standard of care versus Antiviral Treatment and standard of care (control group) in Hospitalized Patients with Pneumonia and COVID-19 Infection.

NCT04675086
Conditions
  1. Covid19
  2. Pneumonia, Viral
Interventions
  1. Drug: alpha1-proteinase inhibitor
  2. Drug: Antiviral Agents
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Duration of new non-invasive ventilation or high flow oxygen use (measured by days)

Time: 365 Days

Secondary Outcomes

Measure: Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized

Time: 1 Year

Measure: The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24

Time: 10 Days, 17 Days, & 24 Days

Measure: The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10.

Time: 10 Days

Measure: The percentage of subjects that required mechanical ventilation during the treatment period.

Time: 1 Year

Measure: The percent of patients with a SOFA score between 0-6 during treatment period.

Time: 1 Year

Measure: The percent of mortality during the treatment period.

Time: 1 Year

Measure: Evaluate the need, dosage and duration of vasopressors (number of days and average daily dose).

Time: 1 Year

Measure: Number of Days fever free (defined by temperature of <100°F (oral) for 24 hours)

Time: 1 Year

Measure: To evaluate the average number of days in the ICU

Time: 1 Year

Measure: To evaluate the average number of days in the hospital

Time: 1 Year

Measure: To evaluate the number of days with a PO2/FiO2 <300 or other parameters decided on with oxygen

Time: 1 Year

Measure: The risk of coagulopathy by measuring Prothrombin time & Partial Thromboplastin time

Time: 1 Year

Measure: The risk of coagulopathy by measuring D-Dimer

Time: 1 Year

Measure: The risk of coagulopathy by measuring Platelet Counts

Time: 1 Year

Other Outcomes

Measure: The percentage of patients with lung fibrosis or worsening of lung fibrosis from screening to Day 10 and Day 24 (as assessed by CT).

Time: 10 Days, 17 Days, & 24 Days

Measure: Maximal inspiratory pressure (MIP) at Day 10, Day 17 and Day 24.

Time: 10 Days, 17 Days, & 24 Days

Measure: Maximal expiratory pressure (MEP) at Day 10, Day 17, and Day 24.

Time: 10 Days, 17 Days, & 24 Days

Measure: Muscle strength assessment at Day 10, Day 17 and Day 24.

Time: 10 Days, 17 Days, & 24 Days

Description: Pharmacokinetics of Aralast NP levels will be drawn to determine if there is a correlation between that and the other endpoints listed above.

Measure: Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and the other listed clinical endpoints at Days 1, 3, 5, 7, 9 and 17.

Time: 1 Day, 3 Days, 5 Days, 7 Days, 9 Days, & 17 Days

Measure: Correlation between plasma exposure of Aralast NP (Pharmacokinetics) and biomarker endpoints (Pharmacodynamics) at Days 1, 6, 10 and 17

Time: 1 Day, 6 Days, 10 Days, & 17 Days
366 Efficacy and Safety of Intravenously Administered hzVSF-v13 in Patients With COVID-19 Pneumonia: a Phase II, Proof of Concept, Multicentre, Randomized, Parallel-group, Double-blind, Placebo-controlled Study

Preliminarily investigate the safety and efficacy of two doses of hzVSF-v13 + SOC vs. placebo + SOC for the treatment of COVID-19 pneumonia.

NCT04676971
Conditions
  1. COVID-19
Interventions
  1. Drug: hzVSF-v13
  2. Drug: Placebo (Normal saline solution)
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: A patient will be considered a clinical failure if on Day 28 the patient is dead, intubated and/or in ICU.

Measure: Clinical failure at Day 28

Time: Day 28

Secondary Outcomes

Description: Clinical improvement is defined as a decrease of at least two points on the WHO ordinal scale from the Day 1 visit to the Day 28 visit.

Measure: Clinical Improvement, defined as a decrease of at least 2 points on the World Health Organization (WHO) ordinal scale

Time: Day 28

Description: Overall survival (OS), defined as the time from randomization to the date of death due to any cause, will be analysed by means of Kaplan-Meier methodology.

Measure: Rate of overall survival (OS) at Day 28 and Day 60

Time: Day 28, Day 60

Description: The incidence of AEs will be tabulated by MedDRA System Organ Class and Preferred Term. The incidence of AEs will also be summarised by System Organ Class, Preferred Term, and severity (based on NCI CTCAE v5.0 grades)

Measure: Incidence and severity of adverse events according to NCI CTCAE v5.0

Time: Day 60

HPO Nodes


HP:0002090: Pneumonia
Genes 280
TLL1 CHD7 TGIF1 KMT2D ACP5 PIGN JAK3 NOS1 SFTPB SRP54 MS4A1 NODAL USB1 CD79B SGCG ACTC1 CASP8 TGFB1 OFD1 CD19 CD247 NHLRC1 SHH NTRK1 EGFR LAMA3 PLOD1 FANCF JAK3 RAG2 PGM3 CACNA1C BTK IL2RG PIK3CD CREBBP KCNJ6 FMO3 ACTA1 TNFSF12 GATA6 ZAP70 PLOD1 UNC119 FGF8 GAS1 DNAI1 WAS GNPTAB FOXH1 CYBC1 LAMC2 RAG1 PEPD PDHA1 PMM2 PAFAH1B1 CD19 CD3D SIX3 CD81 DLL1 LTBP3 EP300 TNFRSF13B SIX3 GLI2 SMARCD2 TIMM8A MYH6 DCLRE1C ABCA3 IL7R TBC1D24 STAT3 CFB FOXH1 FOXP3 FCGR2A P4HTM AP3B1 POLA1 TK2 CDON PKHD1 TAF1 CDON NIPBL GRHL3 GAS1 EFEMP2 CRLF1 SLC35A1 SLC25A24 DOCK8 ZIC2 LEP AFF4 DDR2 CD3E PTPRC BLM RNU4ATAC TNFRSF13C KNSTRN CDON SELENON FOXH1 ORC6 RAG1 RNF168 SHH DISP1 CYBA IL7R CARD11 LONP1 COL11A2 CR2 FGF8 ZIC2 CARD11 CYBB NBN ICOS DNAJC21 DNMT3B DISP1 TGIF1 HLA-DQB1 ADA SETBP1 MED25 FOXH1 SLC35C1 ACADVL TDGF1 PNP SP110 SMC1A ICOS SREBF1 TDGF1 NBN DCLRE1C ALMS1 GLI2 MCIDAS FGF8 NCF1 RAG1 PTCH1 NADK2 IL2RG ZBTB24 ZAP70 GLI2 FGFR1 GAS1 TNFRSF13B GAS1 IFNGR1 CFTR COL11A2 CR2 SAMD9 CD247 TGIF1 TREX1 CARMIL2 TCIRG1 BLNK UBB SRP54 LAMB3 DISP1 RMRP TNFRSF13C NFKB1 STAG2 IRF8 PTCH1 SIX3 KPTN TBX20 TDGF1 CSPP1 IGHM BTK NFIX RNU4ATAC CXCR4 NFKB2 RAC1 CD27 TGIF1 ADA TBX20 ZIC2 MTHFD1 RAG2 GATA4 TNFRSF11A DZIP1L FGF8 KIAA0586 SHH TDGF1 RYR1 ODAD1 WDR1 CREBBP CITED2 DLL1 NCF2 TBCD SHH NODAL RAC2 SIX3 GBA PTCH1 DNAI2 ZIC2 TNFRSF13C ALMS1 PURA STAG2 DLL1 SBDS ICOS EFL1 ACP5 SFTPC CFAP410 MASP2 IL2RG IGLL1 AFF4 BTK LIG4 NFKB2 WDR19 CD55 CDON GAS8 EPM2A NKX2-1 RNF125 DCLRE1C NODAL LRBA ELANE MAN2B1 DLL1 PTCH1 HLA-DQA1 EXTL3 SLC35C1 MAN2B1 FOXN1 PRKCD GLI2 RANBP2 MID1 IL2RG FBLN5 NKX2-5 NODAL GFI1 TNFSF12 RAG2 ADA IL21R KDM6A OSTM1 ASAH1 DISP1 PANK2 FGFR1
SNP 0

HPO

Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


HPO Nodes


HP:0002090: Pneumonia
Genes 280
TLL1 CHD7 TGIF1 KMT2D ACP5 PIGN JAK3 NOS1 SFTPB SRP54 MS4A1 NODAL USB1 CD79B SGCG ACTC1 CASP8 TGFB1 OFD1 CD19 CD247 NHLRC1 SHH NTRK1 EGFR LAMA3 PLOD1 FANCF JAK3 RAG2 PGM3 CACNA1C BTK IL2RG PIK3CD CREBBP KCNJ6 FMO3 ACTA1 TNFSF12 GATA6 ZAP70 PLOD1 UNC119 FGF8 GAS1 DNAI1 WAS GNPTAB FOXH1 CYBC1 LAMC2 RAG1 PEPD PDHA1 PMM2 PAFAH1B1 CD19 CD3D SIX3 CD81 DLL1 LTBP3 EP300 TNFRSF13B SIX3 GLI2 SMARCD2 TIMM8A MYH6 DCLRE1C ABCA3 IL7R TBC1D24 STAT3 CFB FOXH1 FOXP3 FCGR2A P4HTM AP3B1 POLA1 TK2 CDON PKHD1 TAF1 CDON NIPBL GRHL3 GAS1 EFEMP2 CRLF1 SLC35A1 SLC25A24 DOCK8 ZIC2 LEP AFF4 DDR2 CD3E PTPRC BLM RNU4ATAC TNFRSF13C KNSTRN CDON SELENON FOXH1 ORC6 RAG1 RNF168 SHH DISP1 CYBA IL7R CARD11 LONP1 COL11A2 CR2 FGF8 ZIC2 CARD11 CYBB NBN ICOS DNAJC21 DNMT3B DISP1 TGIF1 HLA-DQB1 ADA SETBP1 MED25 FOXH1 SLC35C1 ACADVL TDGF1 PNP SP110 SMC1A ICOS SREBF1 TDGF1 NBN DCLRE1C ALMS1 GLI2 MCIDAS FGF8 NCF1 RAG1 PTCH1 NADK2 IL2RG ZBTB24 ZAP70 GLI2 FGFR1 GAS1 TNFRSF13B GAS1 IFNGR1 CFTR COL11A2 CR2 SAMD9 CD247 TGIF1 TREX1 CARMIL2 TCIRG1 BLNK UBB SRP54 LAMB3 DISP1 RMRP TNFRSF13C NFKB1 STAG2 IRF8 PTCH1 SIX3 KPTN TBX20 TDGF1 CSPP1 IGHM BTK NFIX RNU4ATAC CXCR4 NFKB2 RAC1 CD27 TGIF1 ADA TBX20 ZIC2 MTHFD1 RAG2 GATA4 TNFRSF11A DZIP1L FGF8 KIAA0586 SHH TDGF1 RYR1 ODAD1 WDR1 CREBBP CITED2 DLL1 NCF2 TBCD SHH NODAL RAC2 SIX3 GBA PTCH1 DNAI2 ZIC2 TNFRSF13C ALMS1 PURA STAG2 DLL1 SBDS ICOS EFL1 ACP5 SFTPC CFAP410 MASP2 IL2RG IGLL1 AFF4 BTK LIG4 NFKB2 WDR19 CD55 CDON GAS8 EPM2A NKX2-1 RNF125 DCLRE1C NODAL LRBA ELANE MAN2B1 DLL1 PTCH1 HLA-DQA1 EXTL3 SLC35C1 MAN2B1 FOXN1 PRKCD GLI2 RANBP2 MID1 IL2RG FBLN5 NKX2-5 NODAL GFI1 TNFSF12 RAG2 ADA IL21R KDM6A OSTM1 ASAH1 DISP1 PANK2 FGFR1
SNP 0

Reports

Data processed on December 13, 2020.

An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.

Drug Reports   MeSH Reports   HPO Reports  

Interventions

4,818 reports on interventions/drugs

MeSH

706 reports on MeSH terms

HPO

306 reports on HPO terms

All Terms

Alphabetical index of all Terms

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