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Coronavirus Infections (819) Severe Acute Respiratory Syndrome (567) Infection (472) Pneumonia (366) Communicable Diseases (199) Respiratory Distress Syndrome, Adult (179) Acute Lung Injury (143) Respiratory Distress Syndrome, Newborn (143) Respiratory Insufficiency (132) Syndrome (105) Virus Diseases (90) Pneumonia, Viral (82) Depression (67) Critical Illness (62) Anxiety Disorders (41) Cardiovascular Diseases (36) Emergencies (36) Respiratory Tract Infections (36) Stress, Psychological (31) Hypoxia (30) Inflammation (30) Lung Injury (30) Neoplasms (30) Wounds and Injuries (30) Stress Disorders, Post-Traumatic (29) Thrombosis (28) Diabetes Mellitus (26) Disease (26) Respiratory Tract Diseases (26) Depressive Disorder (25) Stress Disorders, Traumatic (25) Lung Diseases (23) Acute Kidney Injury (22) Disease Progression (22) Mental Disorders (21) Olfaction Disorders (20) Respiration Disorders (20) Burnout, Psychological (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) Dyspnea (12) Fibrosis (12) Influenza, Human (12) Arthritis, Rheumatoid (11) Rheumatic Diseases (11) Venous Thrombosis (11) Burnout, Professional (9) Chronic Pain (9) Cognitive Dysfunction (9) Collagen Diseases (9) Diabetes Mellitus, Type 1 (9) Heart Failure (9) Myocardial Infarction (9) Pneumonia, Ventilator-Associated (9) Pregnancy Complications (9) Problem Behavior (9) Venous Thromboembolism (9) Vitamin D Deficiency (9) Infarction (8) Liver Diseases (8) Lung Diseases, Obstructive (8) Multiple Sclerosis (8) Myocarditis (8) Parasomnias (8) RNA Virus Infections (8) Sclerosis (8) Sepsis (8) Autoimmune Diseases (7) Convalescence (7) Depression, Postpartum (7) Dyssomnias (7) Heart Diseases (7) Hematologic Neoplasms (7) Infertility (7) Inflammatory Bowel Diseases (7) Lymphopenia (7) Pulmonary Disease, Chronic Obstructive (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) Adenoviridae Infections (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) Nervous System Diseases (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) 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Diseases (3) Migraine Disorders (3) Muscle Weakness (3) Myeloproliferative Disorders (3) Myocardial Ischemia (3) Myofascial Pain Syndromes (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 Wake Disorders (3) Spinal Cord Injuries (3) Spondylarthritis (3) Systemic Inflammatory Response Syndrome (3) Taste Disorders (3) Acute Disease (2) Alcohol Drinking (2) Alopecia (2) Amyotrophic Lateral Sclerosis (2) Anorexia (2) Anorexia Nervosa (2) Arteritis (2) Asymptomatic Infections (2) Atrial Fibrillation (2) Atrophy (2) Bacteremia (2) Behcet Syndrome (2) Brain Injuries, Traumatic (2) Carcinoma, Renal Cell (2) Cerebral Palsy (2) Child Development Disorders, Pervasive (2) Cholangiocarcinoma (2) Cholangitis (2) Clinical Deterioration (2) Common Cold (2) Compassion Fatigue (2) Congenital Abnormalities (2) Conjunctivitis (2) Constriction, Pathologic (2) Coronavi (2) Dementia (2) Depressive Disorder, Major (2) Developmental Disabilities (2) Diarrhea (2) Drug-Related Side Effects and Adverse Reactions (2) Encephalitis (2) Endocrine System Diseases (2) Esophageal Neoplasms (2) Eye Diseases (2) Fever (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) Hypothermia (2) Idiopathic Pulmonary Fibrosis (2) Infertility, Male (2) Intestinal Diseases (2) Ischemia (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) Muscular Atrophy (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) Osteoporosis (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) Scleroderma, Diffuse (2) Scleroderma, Systemic (2) Seizures (2) Shock, Septic (2) Skin Diseases (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) Adenocarcinoma (1) Adjustment Disorders (1) Adrenal Insufficiency (1) Agoraphobia (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) 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) 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) Com (1) Communicable Diseases, Emerging (1) Communication Disorders (1) Consciousness Disorders (1) Conversion Disorder (1) Coron (1) Coronavirus Infect (1) Cr (1) Crohn Disease (1) Deafness (1) Death, Sudden, Cardiac (1) Dental Caries (1) Depressive Disorder, Treatment-Resistant (1) Dermatitis (1) DiGeorge Syndrome (1) Diabetes Complications (1) Digestive System Neoplasms (1) Diphtheria (1) Down Syndrome (1) Dyskinesias (1) Dyspareunia (1) Dysphonia (1) Emergen (1) Emergence Delirium (1) Emphysema (1) Endocarditis (1) Endometrial Neoplasms (1) Endometriosis (1) Endophthalmitis (1) Endotoxemia (1) Epilepsy (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) Gastrointestinal Neoplasms (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) Hyp (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) Inf (1) Infant, Newborn, Diseases (1) Infe (1) Infec (1) Infecti (1) Infertility, Female (1) Intellectual Disability (1) Intestinal Atresia (1) Intestinal Neoplasms (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 Dystrophies (1) Musculoskeletal Diseases (1) Myalgia (1) Mycoses (1) Myocardial Reperfusion Injury (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) Neurodegenerative Diseases (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) Pn (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) Renal Insufficie (1) Reperfusion Injury (1) Resp (1) Respi (1) Respiratory Distress Sy (1) Respiratory Syncytial Virus Infections (1) Retinal Vein Occlusion (1) Rupture (1) Sarcoidosis (1) Scleroderma, Localized (1) Se (1) Shock, Cardiogenic (1) Shoulder Fractures (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) Tracheal Stenosis (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)

D012128: Respiratory Distress Sy

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 (451)


Name (Synonyms) Correlation
drug341 Azithromycin Wiki 0.22
drug2490 Placebo Wiki 0.16
drug139 Acalabrutinib Wiki 0.15
Name (Synonyms) Correlation
drug1507 Hydroxychloroquine Wiki 0.15
drug133 Abatacept Wiki 0.13
drug130 AZD7442 Wiki 0.13
drug193 Allocetra-OTS Wiki 0.13
drug3084 Sevoflurane Wiki 0.11
drug313 Atorvastatin Wiki 0.11
drug3308 TD-0903 Wiki 0.11
drug146 Acebilustat Wiki 0.11
drug338 Ayurveda Wiki 0.11
drug208 Ampion Wiki 0.11
drug122 AVIGAN 200 MG Film Tablets Wiki 0.11
drug171 Aerobic Exercise Training Wiki 0.11
drug2011 Mesenchymal Stromal Cells Wiki 0.09
drug2831 Remestemcel-L Wiki 0.09
drug2019 Mesenchymal stromal cells Wiki 0.09
drug119 AV-COVID-19 Wiki 0.09
drug243 Anti-SARS-CoV2 Serology Wiki 0.09
drug3354 Telmisartan Wiki 0.09
drug1556 Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) Wiki 0.07
drug251 Antibody test (SARS-CoV2) Wiki 0.07
drug1575 IC14, a monoclonal antibody against CD14 Wiki 0.07
drug162 Additional biological samples Wiki 0.07
drug242 Anti-SARS-CoV-2 immunoglobulin Wiki 0.07
drug121 AVIGAN Wiki 0.07
drug181 Aerosolized All-Trans Retinoic acid plus oral Tamoxifen Wiki 0.07
drug177 Aerosolized 13 cis retinoic acid Wiki 0.07
drug1107 ECCO2R Wiki 0.07
drug188 Airwave Oscillometry Wiki 0.07
drug1160 Electro impedance tomography Wiki 0.07
drug2895 Ruxolitinib administration Wiki 0.07
drug3850 glenzocimab Wiki 0.07
drug767 Choice of Assignment: Opt-in Wiki 0.07
drug1722 Invasive mechanical ventilation Wiki 0.07
drug156 Activity list Wiki 0.07
drug1117 EIT-Group Wiki 0.07
drug1780 LAU-7b Wiki 0.07
drug520 Brexanolone Wiki 0.07
drug273 Aprepitant injectable emulsion Wiki 0.07
drug443 Biological collection (patients co infected HIV Sras-CoV-2) Wiki 0.07
drug2694 Pulmonary Vascular Permeability Index Wiki 0.07
drug131 AZVUDINE Wiki 0.07
drug3589 Vehicle + Heparin along with best supportive care Wiki 0.07
drug1384 Glycine Wiki 0.07
drug28 1: ILT101 Wiki 0.07
drug1157 Electrical Impedance tomography Wiki 0.07
drug325 Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki 0.07
drug3525 UCMSCs Wiki 0.07
drug178 Aerosolized 13 cis retinoic acid plus Inhalation Inhaled testosterone Wiki 0.07
drug300 Assessment of lung mechanics and heart-lung interactions Wiki 0.07
drug240 Anti-SARS-CoV-2 convalescent plasma Wiki 0.07
drug258 Antioxidation Therapy Wiki 0.07
drug176 Aerosol-reducing Mask Wiki 0.07
drug3229 Statins (Cardiovascular Agents) Wiki 0.07
drug3452 Traditional Proning Arm Wiki 0.07
drug1820 Lidocaine 2% Wiki 0.07
drug216 Anakinra and Ruxolitinib (Advanced stage 3) Wiki 0.07
drug432 Best supportive care" which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy Wiki 0.07
drug1267 FAVICOVIR 200 mg Film Tablet Wiki 0.07
drug2171 Neuromuscular Blocking Agents Wiki 0.07
drug214 Anakinra Prefilled Syringe Wiki 0.07
drug744 Chat-based support Wiki 0.07
drug1144 Economic benefit message Wiki 0.07
drug107 ARFC mask Wiki 0.07
drug985 Dapagliflozin Wiki 0.07
drug1803 Lateral Position (left and right lateral decubitus) Wiki 0.07
drug310 Asynchronies detection Wiki 0.07
drug4012 poractant alfa Wiki 0.07
drug2133 NaCl 0.9% Wiki 0.07
drug2401 Pacebo: Calcium citrate Wiki 0.07
drug323 Auricular percutaneous neurostimulation Wiki 0.07
drug3828 eculizumab Wiki 0.07
drug1846 Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki 0.07
drug2847 Respiratory Mechanics Wiki 0.07
drug262 Antroquinonol Wiki 0.07
drug2872 Ringer's lactate Wiki 0.07
drug187 AirGo Respiratory Monitor Wiki 0.07
drug334 Awake Prone Positioning Wiki 0.07
drug1026 Dexamethasone and Hydroxychloroquine Wiki 0.07
drug211 Anakinra +/- Ruxolitinib (stages 2b/3) Wiki 0.07
drug294 Assessing antibody responses, neutralizing capacity and memory B-cell function Wiki 0.07
drug923 Corticosteroids and Derivatives Wiki 0.07
drug3115 Six-minute walk test (6MWT) Wiki 0.07
drug505 Bovine Lipid Extract Surfactant Wiki 0.07
drug15 0.9% Sodium-chloride Wiki 0.07
drug2589 Plethysmography & DLCO Wiki 0.07
drug1380 Gimsilumab Wiki 0.07
drug98 ARCT-021 Dose 2 Wiki 0.07
drug2551 Placebo of excipient(s) will be administered Wiki 0.07
drug3200 Standard of care (Paracetamol) Wiki 0.07
drug765 Choice of Assignment: Active Choice Wiki 0.07
drug3492 Trust in science message Wiki 0.07
drug2432 Pectin Wiki 0.07
drug1603 Ibuprofen Wiki 0.07
drug1004 Decidual Stromal Cells (DSC) Wiki 0.07
drug222 Anesthesia management Wiki 0.07
drug101 ARCT-021 Dose Regimen 1 Wiki 0.07
drug114 AT-527 Wiki 0.07
drug1264 Extravascular Lung Water Index Wiki 0.07
drug173 Aerobic training Wiki 0.07
drug339 Ayurvedic Kadha Wiki 0.07
drug700 Capnography Wiki 0.07
drug1024 Dexamethasone (high dose) Wiki 0.07
drug100 ARCT-021 Dose 4 Wiki 0.07
drug1149 Education Wiki 0.07
drug1548 Hydroxychloroquine plus standard preventive measures Wiki 0.07
drug3474 Transpulmonary thermodilution Wiki 0.07
drug138 Acacia Senegal Wiki 0.07
drug2158 Nebulised heparin Wiki 0.07
drug2662 Prone decubitus Wiki 0.07
drug97 ARCT-021 Dose 1 Wiki 0.07
drug241 Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki 0.07
drug296 Assessment of Dietary Changes in Adults in the Quarantine Wiki 0.07
drug4132 vadadustat Wiki 0.07
drug161 Additional and minimal collection of products of the human body carried out during a sample for standard of care Wiki 0.07
drug1373 Gas exchanges at different PEEP Wiki 0.07
drug1435 Hemodynamics changes at different PEEP Wiki 0.07
drug1336 Follow up calls Wiki 0.07
drug43 2: Placebo Comparator Wiki 0.07
drug393 BVA-100 Wiki 0.07
drug120 AVICOD 200 MG Film Tablet Wiki 0.07
drug2695 Pulmonary and Motor Rehabilitation Wiki 0.07
drug3383 The standard therapy Wiki 0.07
drug3564 V/Q Vest Wiki 0.07
drug167 Administration of Equine immunoglobulin anti SARS-CoV-2 Wiki 0.07
drug1032 Diabetes type 2 Wiki 0.07
drug2527 Placebo Subcutaneous Solution Wiki 0.07
drug116 ATI-450 Wiki 0.07
drug2513 Placebo Atrovastatin Wiki 0.07
drug1013 DeltaRex-G Wiki 0.07
drug180 Aerosolized All trans retinoic acid Wiki 0.07
drug3709 Zofin Wiki 0.07
drug260 Antithrombotic Therapy (anticoagulant and/or antiplatelet) before admission for Covid19 Wiki 0.07
drug2723 Quasistatic pressure-volume curve Wiki 0.07
drug223 Anger message Wiki 0.07
drug129 AZD1656 Wiki 0.07
drug1865 Low Dose (10 mg) Control Wiki 0.07
drug2657 Prolonged Proned Positioning Wiki 0.07
drug2419 Patient Education Wiki 0.07
drug3157 St. George's Respiratory Questionnaire (SGRQ) Wiki 0.07
drug1475 Hiking challenge Wiki 0.07
drug106 ARDSNet Wiki 0.07
drug2260 Not bravery message Wiki 0.07
drug3439 Tocilizumab Prefilled Syringe Wiki 0.07
drug480 Blood group determination Wiki 0.07
drug1721 Intubation Box Wiki 0.07
drug1344 Freestyle Libre 14 day CGM system Wiki 0.07
drug2852 Respiratory monitoring Wiki 0.07
drug3799 consultation Wiki 0.07
drug2840 Removal of dead space filter Wiki 0.07
drug3665 Wharton's jelly derived Mesenchymal stem cells. Wiki 0.07
drug3596 Verapamil Wiki 0.07
drug2560 Placebo plus standard preventive measures Wiki 0.07
drug1427 Health warning leaflet Wiki 0.07
drug203 Alvelestat Wiki 0.07
drug721 Cell therapy protocol 2 Wiki 0.07
drug2531 Placebo capsules Wiki 0.07
drug272 Apremilast placebo Wiki 0.07
drug33 2 post-mortem transcutaneous lung biopsies (1 anterior ; 1 posterior) using anatomical landmarks Wiki 0.07
drug1452 High PEEP with end inspiratory pause Wiki 0.07
drug2535 Placebo control + best supportive care Wiki 0.07
drug1871 Low PEEP - FiO2 high Wiki 0.07
drug1876 Low dose Low molecular weight heparin or Placebo Wiki 0.07
drug125 AVM0703 Wiki 0.07
drug219 Analogs, Prostaglandin E1 Wiki 0.07
drug4089 standard procedure Wiki 0.07
drug2547 Placebo of FX06 Wiki 0.07
drug112 AT-001 Wiki 0.07
drug1500 Human umbilical cord mesenchymal stem cells + best supportive care Wiki 0.07
drug124 AVIGAN 200 mg Film Tablets Wiki 0.07
drug295 Assessing impact of COVID19 Wiki 0.07
drug283 Arterial blood gas Wiki 0.07
drug194 Allogeneic NK transfer Wiki 0.07
drug3848 gammaCore® Sapphire (non-invasive vagus nerve stimulator) Wiki 0.07
drug3127 Sodium Nitrite Wiki 0.07
drug834 Community interest message Wiki 0.07
drug169 Adsorbed COVID-19 (inactivated) Vaccine Wiki 0.07
drug163 Adenosine Wiki 0.07
drug340 Azinc Wiki 0.07
drug286 Ascorbic Acid Wiki 0.07
drug1268 FAVIR 200 MG FT Wiki 0.07
drug1656 Infusion IV of Mesenchymal Stem cells Wiki 0.07
drug1664 Inhaled sedation Wiki 0.07
drug1016 Descartes 30 Wiki 0.07
drug3432 Tocilizumab +/- ruxolitinib (stages 2b/3) Wiki 0.07
drug3570 VIB7734 Wiki 0.07
drug2164 Nebulized administration of RLF-100 or Placebo Wiki 0.07
drug3563 V/Q SPECT-CT Wiki 0.07
drug1659 Inhaled ILOPROST Wiki 0.07
drug1821 Life2000® Ventilator Wiki 0.07
drug3646 WFI 5% glucose Wiki 0.07
drug3208 Standard of care. Wiki 0.07
drug2799 Razuprotafib Subcutaneous Solution Wiki 0.07
drug165 AdimrSC-2f Wiki 0.07
drug1720 Intravenous sedation Wiki 0.07
drug4058 risk factors Wiki 0.07
drug3172 Standard Mask Wiki 0.07
drug2371 PEEP trial Wiki 0.07
drug3710 ZofinTM (OrganicellTM Flow) Wiki 0.07
drug1949 MakAir Wiki 0.07
drug189 Airway pressure release ventilation Wiki 0.07
drug212 Anakinra 100Mg/0.67Ml Inj Syringe Wiki 0.07
drug3136 Sofosbuvir/daclatasvir Wiki 0.07
drug2528 Placebo Tablet Wiki 0.07
drug1845 Lopinavir 200 MG / Ritonavir 50 MG [Kaletra] Wiki 0.07
drug175 Aerosol Box Wiki 0.07
drug157 Ad26.COV2.S Wiki 0.07
drug2668 Propofol Wiki 0.07
drug2846 Respiratory Exercise Training Wiki 0.07
drug2661 Prone Positioning (PP) Wiki 0.07
drug672 CTUS examination Wiki 0.07
drug2277 Obesity Wiki 0.07
drug3681 XCEL-UMC-BETA Wiki 0.07
drug127 AWARD plus COVID-specific advice Wiki 0.07
drug1102 During COVID-19 Pandemic Wiki 0.07
drug315 Atorvastatin 20mg Wiki 0.07
drug102 ARCT-021 Dose Regimen 2 Wiki 0.07
drug490 Blood samples collection Wiki 0.07
drug3155 Spironolactone 100mg Wiki 0.07
drug3898 intermediate dose Enoxaparin/ unfractionated heparin Wiki 0.07
drug1453 High PEEP without end inspiratory pause Wiki 0.07
drug252 Antibody testing Wiki 0.07
drug2251 Normal Saline Infusion + standard of care Wiki 0.07
drug4081 specific exercise rehabilitation treatment Wiki 0.07
drug878 Control message Wiki 0.07
drug960 Cytokine Adsorption Wiki 0.07
drug3870 hydrocortisone Wiki 0.07
drug3694 Zilucoplan Wiki 0.07
drug1861 Losartan Wiki 0.07
drug150 Active COVID-19 disease Wiki 0.07
drug3597 Veru-111 Wiki 0.07
drug144 Accuchek Inform II platform Wiki 0.07
drug190 Alexa Amazon Wiki 0.07
drug123 AVIGAN 200 mg FT Wiki 0.07
drug147 Acetyl L-Carnitine Wiki 0.07
drug221 Anatolian Propolis Wiki 0.07
drug3209 Standard oxygen therapy Wiki 0.07
drug115 ATAFENOVIR 200 MG KAPSUL Wiki 0.07
drug4020 prone position Wiki 0.07
drug1111 ECMO Implantation Wiki 0.07
drug137 Abivertinib Wiki 0.07
drug3541 Umbilical cord Wharton's jelly-derived human Wiki 0.07
drug3183 Standard Ventilation Strategy Wiki 0.07
drug1224 Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells Wiki 0.07
drug1334 Folic Acid Wiki 0.07
drug179 Aerosolized 13 cis retinoic acid plus Inhalation administration by nebulization captopril 25mg Wiki 0.07
drug2480 Physiology Wiki 0.07
drug1069 Dociparastat sodium Wiki 0.07
drug1096 Drug: Standard treatment Standard treatment Wiki 0.07
drug3050 Senicapoc Wiki 0.07
drug257 Antihypertensive Agents Wiki 0.07
drug205 Amiodarone Wiki 0.07
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Correlated MeSH Terms (41)


Name (Synonyms) Correlation
D012127 Respiratory Distress Syndrome, Newborn NIH 0.89
D055371 Acute Lung Injury NIH 0.89
D013577 Syndrome NIH 0.47
Name (Synonyms) Correlation
D055370 Lung Injury NIH 0.31
D045169 Severe Acute Respiratory Syndrome NIH 0.12
D011665 Pulmonary Valve Insufficiency NIH 0.11
D018352 Coronavirus Infections NIH 0.11
D011654 Pulmonary Edema NIH 0.09
D011014 Pneumonia NIH 0.09
D014947 Wounds and Injuries NIH 0.08
D012770 Shock, Cardiogenic NIH 0.07
D063806 Myalgia NIH 0.07
D007040 Hypoventilation NIH 0.07
D000071257 Emergence Delirium NIH 0.07
D007249 Inflammation NIH 0.07
D004417 Dyspnea NIH 0.06
D011024 Pneumonia, Viral NIH 0.06
D012769 Shock, NIH 0.06
D000075902 Clinical Deterioration NIH 0.05
D009362 Neoplasm Metastasis NIH 0.05
D007035 Hypothermia NIH 0.05
D018746 Systemic Inflammatory Response Syndrome NIH 0.04
D045888 Ganglion Cysts NIH 0.04
D016638 Critical Illness NIH 0.04
D018754 Ventricular Dysfunction NIH 0.04
D012818 Signs and Symptoms, Respiratory NIH 0.04
D018487 Ventricular Dysfunction, Left NIH 0.04
D007154 Immune System Diseases NIH 0.03
D003693 Delirium NIH 0.03
D009102 Multiple Organ Failure NIH 0.03
D014115 Toxemia NIH 0.03
D003141 Communicable Diseases NIH 0.03
D007239 Infection NIH 0.03
D000860 Hypoxia NIH 0.03
D018805 Sepsis NIH 0.03
D006333 Heart Failure NIH 0.02
D058186 Acute Kidney Injury NIH 0.02
D014777 Virus Diseases NIH 0.02
D008171 Lung Diseases, NIH 0.02
D009369 Neoplasms, NIH 0.01
D012141 Respiratory Tract Infections NIH 0.01

Correlated HPO Terms (15)


Name (Synonyms) Correlation
HP:0010444 Pulmonary insufficiency HPO 0.11
HP:0002090 Pneumonia HPO 0.09
HP:0100598 Pulmonary edema HPO 0.09
Name (Synonyms) Correlation
HP:0002791 Hypoventilation HPO 0.07
HP:0030149 Cardiogenic shock HPO 0.07
HP:0003326 Myalgia HPO 0.07
HP:0002098 Respiratory distress HPO 0.07
HP:0002045 Hypothermia HPO 0.05
HP:0012418 Hypoxemia HPO 0.03
HP:0100806 Sepsis HPO 0.03
HP:0001635 Congestive heart failure HPO 0.03
HP:0002088 Abnormal lung morphology HPO 0.02
HP:0001919 Acute kidney injury HPO 0.02
HP:0002664 Neoplasm HPO 0.01
HP:0011947 Respiratory tract infection HPO 0.01

Clinical Trials

Navigate: Correlations   HPO

There are 180 clinical trials


1 Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19

Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

NCT04360096
Conditions
  1. SARS-CoV 2
  2. COVID
  3. ARDS
  4. ALI
  5. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  6. Dyspnea
Interventions
  1. Drug: RLF-100 (aviptadil)
  2. Drug: Placebo
  3. Device: Nebulized administration of RLF-100 or Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Sy Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
HPO:Dyspnea Respiratory distress

Primary Outcomes

Description: Progression to ARDS is defined as the need for mechanical ventilation

Measure: Progression to ARDS

Time: 28 days

Secondary Outcomes

Description: Blood PO2 as measured by pulse oximetry

Measure: Blood oxygenation

Time: 28 days

Description: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity

Measure: RDP Dsypnea Scale

Time: 28 days

Description: Distance walked in six minutes

Measure: Distance walked in six minutes

Time: 28 days
2 Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST): An Open Label Dose Escalation Phase 1 Trial Followed by a Randomized, Double-blind, Placebo-controlled Phase 2 Trial (COVID-19)

Acute Respiratory Distress Syndrome (ARDS) causes the lungs to fail due to the collection of fluid in the lungs (pulmonary oedema). ARDS is common in severely ill patients in Intensive Care Units and is associated with a high mortality and a high morbidity in those who survive. ARDS occurs in approximately 20% case of COVID-19 and respiratory failure is the leading cause of mortality. There is a large economic burden with direct healthcare costs, but also indirectly due to the impact on the carer and patient through the patients inability to return to full time employment. There is little evidence for effective drug (pharmacological) treatment for ARDS. There is increasing information that mesenchymal stem cells (MSCs) might be important in treating ARDS. REALIST will investigate if a single infusion of MSCs will help in the treatment of ARDS. The first step will be to first of all determine what dose of MSCs is safe and then divide patients suffering from ARDS into two groups, one of which will get MSCs and the other a harmless dummy (or placebo) infusion, who will then be followed up to determine if lung function improves. If effective this may lead to further research to determine if MSCs are effective in patients with ARDS.

NCT03042143
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Human umbilical cord derived CD362 enriched MSCs
  2. Biological: Placebo (Plasma-Lyte 148)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: OI is a physiological index of the severity of ARDS and measures both impaired oxygenation and the amount of mechanical ventilation delivered

Measure: Oxygenation index (OI)

Time: Day 7

Description: Incidence of SAEs

Measure: Incidence of Serious Adverse Events (SAEs)

Time: 28 days

Secondary Outcomes

Measure: Oxygenation index

Time: Days 4 and 14

Description: SOFA score is a measure of organ failure

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: Days 4, 7 and 14

Description: Crs is a physiological measure of pulmonary function in ARDS

Measure: Respiratory compliance (Crs)

Time: Days 4, 7 and 14

Description: P/F ratio is a physiological measure of pulmonary function in ARDS

Measure: Partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (P/F ratio)

Time: Days 4, 7 and 14

Measure: Driving Pressure

Time: Days 4, 7 and 14

Measure: Extubation and reintubation

Time: Up to day 14 or until the patient is discharged from ICU or the patient dies

Measure: Ventilation free days at day 28

Time: Day 28

Measure: Length of ICU and hospital stay

Time: Until the patient is discharged or the patient dies

Measure: 28-day and 90-day mortality

Time: Up to 28 and 90 days
3 Pilot Randomized Clinical Trial of Therapeutic Hypothermia Plus Neuromuscular Blockade vs. Standard of Care in COVID-19 Patients With Moderate to Severe ARDS - the Cooling to Help Injured Lungs (CHILL) Pilot Study

Acute Respiratory Distress Syndrome (ARDS) is a serious condition that occurs as a complication of medical and surgical diseases, has a mortality of ~40%, and has no known treatment other than optimization of support. Data from basic research, animal models, and retrospective studies, case series, and small prospective studies suggest that therapeutic hypothermia (TH) similar to that used for cardiac arrest may be lung protective in patients with ARDS; however, shivering is a major complication of TH, often requiring paralysis with neuromuscular blocking agents (NMBA) to control. Since the recently completed NHLBI PETAL ROSE trial showed that NMBA had no effect (good or bad) in patients with moderate to severe ARDS, the investigators sought to evaluate whether TH combined with NMBA is beneficial in patients with ARDS. The investigators are scheduled to begin enrolling in a Department of Defense-funded Phase IIb multicenter RCT of TH (core temperature 34-35°C) + NMBA for 48h vs. usual temperature management in patients with ARDS with time on ventilator as the primary outcome. Since COVID-19 is now the most common cause of ARDS, we are conducting a pilot study to examine the safety and feasibility of including patients with COVID-19-associated ARDS in our upcoming trial. In this pilot, we will randomize 20 patients with COVID-19 and ARDS to either TH+NMBA for 48h or usual temperature management. The primary outcome is achieving and maintaining the target temperature. Secondary outcomes include safety, physiologic measures, mortality, hospital and ICU length of stay, and serum biomarkers collected on days 0, 1, 2, 3, 4, and 7.

NCT03376854
Conditions
  1. Respiratory Distress Syndrome, Adult
  2. Sars-CoV2
Interventions
  1. Device: Hypothermia
  2. Drug: Neuromuscular Blocking Agents
  3. Device: Standard of Care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Hypothermia
HPO:Hypothermia

Primary Outcomes

Description: The total time in hours from beginning of cooling to beginning of rewarming during which the patient's core temperature was within the target range of 34-35°C.

Measure: Targeted temperature compliance

Time: Randomization through day 3

Secondary Outcomes

Description: Adverse events expected during cooling, including hemorrhage, bradycardia, and hypotension.

Measure: Adverse event

Time: Randomization through study day 3

Description: Total number of days alive and not admitted to the ICU in the first 28 days after

Measure: 28-day ICU-free days

Time: Calculated at study day 28 or death (whichever occurs first)

Description: 28-day, 60-day, and 90-day mortality

Measure: Survival

Time: calculated at 28, 60, and 90 days

Description: SOFA score excluding neurologic component - based on PaO2/FiO2 (0-4), BP and pressor requirement (0-4), bilirubin level (0-4), platelet count (0-4), and creatinine (0-14) with total composite score 0-20

Measure: non neurologic Sequential Organ Failure (SOFA) scores

Time: At enrollment and study days 1, 2, 3, 4, 7, and 28

Description: Pulse ox reading

Measure: Oxygen saturation (SpO2)

Time: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, 7 and 28

Description: On machine initiated breath

Measure: Plateau airway pressure

Time: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first

Description: Direct ventilator measurement on machine initiated breath

Measure: Mean airway pressure

Time: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first

Description: Plateau pressure - PEEP (machine initiated breath)

Measure: Airway driving pressure

Time: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first

Description: Mean airway pressure x 100 x FiO2/SpO2

Measure: Oxygen saturation index

Time: Measured at enrollment, every 4 hours on enrollment day, then once on day 2, 3, 4, and 7 or until extubation whichever occurs first

Description: Measured continuously from iv catheter, urinary catheter, or esophageal probe.

Measure: Core temperature

Time: Measured continuously and recorded at enrollment, every 2 hours on the day of enrollment, and mornings on study day 2, 3, 4, and 7

Description: 24 hour urine volume

Measure: Urine output

Time: Daily on study day 1, 2, 3, 4, and 7

Description: performed in clinical lab

Measure: comprehensive metabolic panel

Time: Daily on study day 1, 2, 3, 4, and 7

Description: preformed in clinical lab

Measure: Complete blood count with differential count and platelet count

Time: Daily on study day 1, 2, 3, 4, and 7

Description: 10 ml blood draw

Measure: Biomarkers

Time: Daily on study day 1, 2, 3, 4, and 7

Description: performed in clinical lab

Measure: Serum electrolytes

Time: Every 8 hours until study hour 60

Description: Beside blood glucose testing

Measure: Blood glucose

Time: Every 4 hours until study hour 60

Description: Total number of days alive and not on a ventilator in the first 28 days after enrollment

Measure: 28-day ventilator-free days

Time: Calculated at study day 28 or death (whichever occurs first)
4 Careful Ventilation in Acute Respiratory Distress Syndrome

This is a multicenter randomized controlled clinical trial with an adaptive design assessing the efficacy of setting the ventilator based on measurements of respiratory mechanics (recruitability and effort) to reduce Day 60 mortality in patients with acute respiratory distress syndrome (ARDS). The CAVIARDS study is also a basket trial; a basket trial design examines a single intervention in multiple disease populations. CAVIARDS consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (COVID-19 and non-COVID-19 patients). As per a typical basket trial design, the operational structure of both the COVID-19 substudy (CAVIARDS-19) and non-COVID-19 substudy (CAVIARDS-all) is shared (recruitment, procedures, data collection, analysis, management, etc.).

NCT03963622
Conditions
  1. ARDS
Interventions
  1. Other: Respiratory Mechanics
  2. Other: Standard Ventilation Strategy
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The lack of an appropriate surrogate endpoint, and the high baseline mortality rate mandate a multicentre RCT to determine the mortality effects of setting the ventilator based on recruitability and effort compared with conventional ventilation.

Measure: All-cause 60-day mortality

Time: 60 days

Secondary Outcomes

Description: Duration of ventilation in days

Measure: Duration of ventilation

Time: May exceed 60 days

Description: Duration of ICU and hospital stay in days

Measure: Duration of ICU and hospital stay

Time: May exceed 60 days

Description: Organ dysfunction as per the SOFA score

Measure: Number of patients with organ dysfunction

Time: Day 1-7, 14, 21, 28

Description: Barotrauma defined as new onset of pneumothorax

Measure: Number of patients with barotrauma

Time: Up to 60 days

Description: Mortality

Measure: Mortality at ICU discharge, 28 days, and hospital discharge

Time: Up to date of ICU discharge, 28 days, and hospital discharge

Other Outcomes

Description: Biomarkers include interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor receptor 1 (TNFr1), soluble receptor of the advanced glycation end products (sRAGE), and surfactant protein D (SPD). All measured in pg/ml

Measure: The change in biomarker expression

Time: Baseline, 24 and 72 hours
5 Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID-19: a Randomized Clinical Trial

The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (SARS-Cov-2) 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 SARS-CoV-2 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.

NCT04305457
Conditions
  1. Coronavirus Infections
  2. Pneumonia, Viral
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Nitric Oxide
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. 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 patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation

Time: 28 days

Secondary Outcomes

Description: Proportion of deaths from all causes

Measure: Mortality

Time: 28 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), alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.

Measure: Time to clinical recovery

Time: 28 days

Other Outcomes

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

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

Time: 7 days
6 Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

Study Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

NCT04308668
Conditions
  1. Corona Virus Infection
  2. Acute Respiratory Distress Syndrome
  3. SARS-CoV Infection
  4. Coronavirus
  5. Coronavirus Infections
Interventions
  1. Drug: Hydroxychloroquine
  2. Other: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Number of participants at 14 days post enrollment with active COVID19 disease.

Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline

Time: 14 days

Description: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline

Time: 14 days

Secondary Outcomes

Description: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.

Measure: Incidence of Hospitalization

Time: 14 days

Description: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.

Measure: Incidence of Death

Time: 90 days

Description: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.

Measure: Incidence of Confirmed SARS-CoV-2 Detection

Time: 14 days

Description: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.

Measure: Incidence of Symptoms Compatible with COVID19 (possible disease)

Time: 90 days

Description: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.

Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal

Time: 14 days

Description: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Measure: Overall symptom severity at 5 and 14 days

Time: 5 and 14 days

Description: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.

Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry

Time: 14 days
7 Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

This is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).

NCT04311177
Conditions
  1. Corona Virus Infection
  2. Acute Respiratory Distress Syndrome
  3. SARS-CoV Infection
Interventions
  1. Drug: Losartan
  2. Other: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.

Measure: Hospital Admission

Time: 15 days

Secondary Outcomes

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.

Measure: Change in PROMIS Dyspnea scale

Time: 10 days

Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

Measure: Change in SF-12 Physical Composite Score

Time: 10 days

Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

Measure: Change in SF-12 Mental Composite Score

Time: 10 days

Description: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.

Measure: Daily Maximum Temperature

Time: 10 days

Description: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.

Measure: Emergency Department/Clinic Presentations

Time: 28 days

Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. 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: Disease Severity Rating Day 7

Time: 7 days

Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. 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: Disease Severity Rating Day 15

Time: 15 days

Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. 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: Disease Severity Rating Day 28

Time: 28 days

Description: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Oropharyngeal Swab Day 9

Time: 9 days

Description: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Oropharyngeal Swab Day 15

Time: 15 days

Description: Outcome reported as the mean number of days participants in each arm did not require ventilator use.

Measure: Ventilator-Free Days

Time: 28 days

Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.

Measure: Therapeutic Oxygen-Free Days

Time: 28 days

Description: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.

Measure: Need for Hospital Admission at 15 Days

Time: 15 days

Description: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.

Measure: Need for Oxygen Therapy at 15 Days

Time: 15 days
8 ZYESAMI (Aviptadil) for the Treatment of Critical COVID-19 With Respiratory Failure

Novel Corona Virus (SARS-CoV-2) is known to cause Respiratory Failure, which is the hallmark of Acute COVID-19, as defined by the new NIH/FDA classification. Approximately 50% of those who develop Critical COVID-19 die, despite intensive care and mechanical ventilation. Patients with Critical COVID-19 and respiratory failure, currently treated with high flow nasal oxygen, non-invasive ventilation or mechanical ventilation will be treated with ZYESAMI (aviptadil), a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.

NCT04311697
Conditions
  1. Critical COVID-19 With Respiratory Failure
  2. Acute Respiratory Distress Syndrome (ARDS)
  3. Corona Virus Infection
  4. Acute Lung Injury
Interventions
  1. Drug: Aviptadil by intravenous infusion + standard of care
  2. Drug: Normal Saline Infusion + standard of care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury

Primary Outcomes

Description: Cumulative distribution of the time to respiratory failure resolution with concurrent survival through day 28

Measure: Resolution of Respiratory Failure

Time: Day 0 through day 28

Secondary Outcomes

Description: Achievement of score 6-8 on NIAID Ordinal Scale through day 28

Measure: Improvement on NIAID Scale (key secondary measure)

Time: Day 0 through day 28

Description: Survival probability on Kaplan Meier lifetable through day 28 and day 60

Measure: Survival through day 28 and day 60

Time: Day 0 through day 28

Description: Time to discharge from Intensive Care Unit

Measure: Time to ICU discharge

Time: Day 0 through day 28

Description: Time on mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen

Measure: Time on ventilation

Time: Day 0 through day 28

Description: Time to extubation (for those initially on mechanical ventilation)

Measure: Time to extubation

Time: Day 0 through day 28

Description: Time to discharge alive

Measure: Time to discharge alive

Time: Day 0 through day 28 and day 60

Description: Days free of multisystem organ failure

Measure: Multi-organ failure free days

Time: Day 0 through day 28

Other Outcomes

Description: PaO2:FiO2 ratio

Measure: Respiratory Distress while on mechanical ventilation

Time: Day 0 through day 28

Description: Oxygenation index

Measure: Oxygenation index

Time: Day 0 through day 28

Description: Improvement in chest x-ray by RALES score

Measure: Improvement in chest x-ray

Time: Day 0 through day 28

Description: Improvement in IL-6, TNF alpha, and other inflammatory markers

Measure: Improvement in inflammatory markers

Time: Day 0 through day 28
9 Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization

This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.

NCT04312009
Conditions
  1. Corona Virus Infection
  2. Acute Respiratory Distress Syndr
  3. Acute Respiratory Distress Syndrome
  4. SARS-CoV Infection
Interventions
  1. Drug: Losartan
  2. Other: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.

Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days

Time: 7 days

Secondary Outcomes

Description: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.

Measure: Daily Hypotensive Episodes

Time: 10 days

Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

Measure: Hypotension Requiring Vasopressors

Time: 10 days

Description: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.

Measure: Acute Kidney Injury

Time: 10 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). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.

Measure: Sequential Organ Failure Assessment (SOFA) Total Score

Time: 10 days

Description: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.

Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S)

Time: 10 days

Description: Outcome reported as the number of participants who have expired at 28 days post enrollment.

Measure: 28-Day Mortality

Time: 28 days

Description: Outcome reported as the number of participants who have expired at 90 days post enrollment.

Measure: 90-Day Mortality

Time: 90 days

Description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

Measure: ICU Admission

Time: 10 days

Description: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

Measure: Number of Ventilator-Free Days

Time: 10 days

Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

Measure: Number of Therapeutic Oxygen-Free Days

Time: 10 days

Description: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

Measure: Number of Vasopressor-Free Days

Time: 10 days

Description: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.

Measure: Length of ICU Stay

Time: 10 days

Description: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

Measure: Length of Hospital Stay

Time: 10 days

Description: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.

Measure: Incidence of Respiratory Failure

Time: 10 days

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.

Measure: Change in PROMIS Dyspnea scale

Time: 10 days

Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

Measure: Change in SF-12 Physical Composite Score

Time: 10 days

Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

Measure: Change in SF-12 Mental Composite Score

Time: 10 days

Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. 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: Disease Severity Rating

Time: 10 days

Description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Nasopharyngeal Swab Day 9

Time: 9 days

Description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Nasopharyngeal Swab Day 15

Time: 15 days

Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Blood Day 9

Time: 9 days

Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Blood Day 15

Time: 15 days
10 Uppsala Intensive Care Study of Mechanisms for Organ Dysfunction in Covid-19

The study aims to investigate organ dysfunction and biomarkers in patients with suspected or verified COVID-19 during intensive care at Uppsala University Hospital.

NCT04316884
Conditions
  1. COVID-19
  2. Organ Dysfunction Syndrome Sepsis
  3. Organ Dysfunction Syndrome, Multiple
  4. Septic Shock
  5. Acute Kidney Injury
  6. Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Acute Kidney Injury Syndrome Systemic Inflammatory Response Syndrome Multiple Organ Failure
HPO:Acute kidney injury

Primary Outcomes

Description: KDIGO AKI score

Measure: Acute Kidney Injury

Time: During Intensive Care, an estimated average of 10 days.

Secondary Outcomes

Description: Acute Respiratory Distress Syndrome yes/no

Measure: ARDS

Time: During intensive care, an estimated average of 10 days.

Description: Death within 30 days of ICU admission

Measure: 30 day mortality

Time: 30 days

Description: Death within 1 year of ICU admission

Measure: 1 year mortality

Time: 1 year

Description: Development of Chronic Kidney Disease

Measure: Chronic Kidney Disease

Time: 60 days and 1 year after ICU admission

Description: Sequential Organ Failure Score as a continuous variable

Measure: SOFA-score

Time: During Intensive Care, an estimated average of 10 days.
11 The (Norwegian) NOR Solidarity Multicenter Trial on the Efficacy of Different Anti-viral Drugs in SARS-CoV-2 Infected Patients

The (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.

NCT04321616
Conditions
  1. SARS-CoV Infection
  2. COVID 19
  3. Acute Respiratory Distress Syndrome ARDS
Interventions
  1. Drug: Hydroxychloroquine
  2. Drug: Remdesivir
  3. Other: (Standard of Care) SoC
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: All cause in-hospital mortality

Measure: In-hospital mortality

Time: 3 weeks

Secondary Outcomes

Measure: Occurrence and duration of mechanical ventilation

Time: 3 weeks

Measure: Occurrence and duration of intensive care unit (ICU) treatment

Time: 3 weeks

Measure: Duration of hospital admittance

Time: 1 month

Measure: 28 Day mortality

Time: 3 weeks

Measure: Viral clearance as assessed by SARS-CoV-2 PCR in peripheral blood and nasopharyngeal airway speciemen

Time: 3 weeks

Measure: Occurrence of co-infections

Time: 3 weeks

Measure: Occurrence of organ dysfunction

Time: 3 months

Other Outcomes

Measure: Inflammatory and anti-inflammatory mediators as assessed in serum and plasma

Time: Throughout hospitalization

Measure: Markers of extracellular matrix remodeling

Time: Throughout hospitalization and 3 months after remission

Measure: Markers of endothelial activation

Time: Throughout hospitalization

Measure: Markers of platelet activation

Time: Throughout hospitalization
12 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
13 Efficacy of Dexamethasone Treatment for Patients With ARDS Caused by COVID-19

Background: There are no proven therapies specific for Covid-19. The full spectrum of Covid-19 ranges from asymptomatic disease to mild respiratory tract illness to severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure, and death. The efficacy of corticosteroids in viral ARDS remains controversial. Methods: This is an internationally (Spain, Canada, China, USA) designed multicenter, randomized, controlled, open-label clinical trial testing dexamethasone in mechanically ventilated adult patients with established moderate-to-severe ARDS caused by confirmed Covid-19 infection, admitted in a network of Spanish ICUs. Eligible patients will be randomly assigned to receive either dexamethasone plus standard intensive care, or standard intensive care alone. Patients in the dexamethasone group will receive an intravenous dose of 20 mg once daily from day 1 to day 5, followed by 10 mg once daily from day 6 to day 10. The primary outcome is 60-day mortality. The secondary outcome is the number of ventilator-free days at 28 days. All analyses will be done according to the intention-to-treat principle.

NCT04325061
Conditions
  1. Acute Respiratory Distress Syndrome Caused by COVID-19
Interventions
  1. Drug: Dexamethasone
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: All-cause mortality at 60 days after enrollment

Measure: 60-day mortality

Time: 60 days

Secondary Outcomes

Description: Number of ventilator-free days (VFDs) at Day 28 (defined as days being alive and free from mechanical ventilation at day 28 after enrollment, For patients ventilated 28 days or longer and for subjects who die, VFD is 0.

Measure: Ventilator-free days

Time: 28 days
14 Early Prone Positioning Combined With High-Flow Nasal Cannula Versus High-Flow Nasal Cannula in COVID-19 Induced Moderate to Severe ARDS

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and had subsequently spread worldwide. Twenty-nine percent of COVID-19 patients may develop ARDS. Based on the potential beneficial mechanisms of HFNC and PP, whether early use of prone positioning combined with HFNC can avoid the need for intubation in COVID-19 induced moderate to severe ARDS patients needs to be further investigated.

NCT04325906
Conditions
  1. Prone Positioning
  2. High Flow Nasal Cannula
  3. Acute Respiratory Distress Syndrome
  4. Corona Virus Infection
Interventions
  1. Device: high flow nasal cannula (HFNC)
  2. Procedure: Prone positioning (PP)
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: the treatment failure rate of HFNC/HFNC+PP support and clinical requirement for advanced respiratory support

Measure: Treatment failure

Time: 28 days

Measure: Intubation rate

Time: 28 days

Secondary Outcomes

Description: the improvement of SpO2/FIO2 or PaO2/FiO2 from HFNC alone to HFNC+PP

Measure: Efficacy of PP

Time: 28 days
15 COVID-19-associated ARDS Treated With DEXamethasone: an Open-label, Randomized, Controlled Trial: CoDEX (Alliance Covid-19 Brasil III)

The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Most cases are mild or asymptomatic. However, around 5% of all patients develop Acute Respiratory Distress Syndrome (ARDS), which is the leading mortality cause in these patients. Corticosteroids have been tested in deferent scenarios of ARDS, including viral pneumonia, and the early use of dexamethasone is safe and appears to reduce the duration of mechanical ventilation in ARDS patients. Nevertheless, no large, randomized, controlled trial was performed evaluating the role of corticosteroids in patients with ARDS due SARS-CoV2 virus. Therefore, the present study will evaluate the effectiveness of dexamethasone compared to control (no corticosteroids) in patients with moderate and severe ARDS due to SARS-CoV2 virus.

NCT04327401
Conditions
  1. Coronavirus Infection
  2. Pneumonia, Viral
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Dexamethasone
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.

Measure: Ventilator-free days

Time: 28 days after randomization

Secondary Outcomes

Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the 6-point Ordinal Scale, this scale ranges from 1 (Not hospitalized) to 6 (Death) with higher scores meaning worse outcomes.

Measure: Evaluation of the clinical status

Time: 15 days after randomization

Description: All-cause mortality rates at 28 days after randomization.

Measure: All-cause mortality

Time: 28 days after randomization

Description: Number of days of mechanical ventilation from randomization to day 28.

Measure: Mechanical ventilation duration

Time: 28 days after randomization

Description: Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization

Measure: Sequential Organ Failure Assessment (SOFA) Score

Time: Score at 48 hours, 72 hours and 7 days after randomization

Other Outcomes

Description: Intensive Care Unit free days, defined as alive and discharged from the intensive care unit, at 28 days after randomization.

Measure: Intensive Care Unit free days

Time: 28 days after randomization
16 A Randomized, Controlled, Open Label, Multicentre Clinical Trial to Explore Safety and Efficacy of Hyperbaric Oxygen for Preventing ICU Admission, Morbidity and Mortality in Adult Patients With COVID-19

COVID-19 may cause severe pneumonitis that require ventilatory support in some patients, the ICU mortality is as high as 62%. Hospitals do not have enough ICU beds to handle the demand and to date there is no effective cure. We explore a treatment administered in a randomized clinical trial that could prevent ICU admission and reduce mortality. The overall hypothesis to be evaluated is that HBO reduce mortality, increase hypoxia tolerance and prevent organ failure in patients with COVID19 pneumonitis by attenuating the inflammatory response.

NCT04327505
Conditions
  1. SARS (Severe Acute Respiratory Syndrome)
  2. Cytokine Storm
  3. ARDS, Human
  4. COVID-19
  5. Sars-CoV2
  6. Acute Respiratory Failure
Interventions
  1. Drug: Hyperbaric oxygen
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Insufficiency Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: The proportion of subjects admitted to ICU from day 1 to day 30, based on at least one of the following criteria: i) Rapid progression over hours ii) Lack of improvement on high flow oxygen >40L/min or non invasive ventilation with fraction of inspired oxygen (FiO2) > 0.6 iii) Evolving Hypercapnia or increased work of breathing not responding to increased oxygen despite maximum standard of care available outside ICU iv) Hemodynamic instability or multi organ failure with maximum standard of care available outside ICU

Measure: ICU admission

Time: Through study completion 30 days

Secondary Outcomes

Description: Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30.

Measure: 30-day mortality

Time: Through study completion 30 days

Description: Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30

Measure: Time-to-intubation

Time: Through study completion 30 days

Description: Time-to-ICU, i.e. cumulative ICU free days, derived as the number of days from day 1 to ICU, where all ICU free subjects are censored at day 30.

Measure: Time-to-ICU

Time: Through study completion 30 days

Description: Mean change in inflammatory response from day 1 to day 30. White cell count + differentiation Procalcitonin C-Reactive protein Cytokines (IL-6) (if available at local laboratory) Ferritin D-Dimer LDH

Measure: Inflammatory response

Time: Through study completion 30 days

Description: Overall survival (Kaplan-Meier)

Measure: Overall survival

Time: Through study completion 30 days

Other Outcomes

Description: Hospital mortality of any cause, proportion of subjects, from day 1 to day 30.

Measure: Hospital mortality

Time: Through study completion 30 days

Description: Proportion of subjects with ICU mortality, Mortality of any cause in ICU, from day 1 to day 30.

Measure: ICU mortality

Time: From ICU admission to study completion 30 days

Description: Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30.

Measure: Time in Invasive Ventilation

Time: From ICU admission to study completion 30 days

Description: Mean daily NEWS from day 1 to day 30.

Measure: NEWS

Time: Through study completion 30 days

Description: Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30.

Measure: PaO2/FiO2 (PFI)

Time: Through study completion 30 days

Description: Proportion of HBO treatments given vs planned. Proportion of subjects with HBO treatment administered within 24h after enrolment.

Measure: HBO Compliance

Time: Day 1 to day 7

Description: Time-to-discharge from hospital

Measure: Hospital discharge

Time: Through study completion 30 days

Description: Mean oxygen dose per day including HBO and cumulative pulmonary oxygen toxicity expressed as Units of oxygen pulmonary toxicity dose (UPTD) and Cumulative pulmonary toxicity dose (CPTD) from day 1 to day 30.

Measure: Oxygen dose

Time: Through study completion 30 days

Description: Median number of HBO treatments and dose of HBO given, from day 1 to day 7

Measure: HBO dose

Time: Day 1 to day 7

Description: Change in expression of Micro RNA in plasma from day 1 to day 30

Measure: Micro RNA

Time: Through study completion 30 days

Description: Change in gene expression and Micro RNA interactions in Peripheral Blood Mononuclear Cells (PBMC) (20 Subjects) from day 1 to day 30

Measure: Hypoxic response

Time: Through study completion 30 days

Description: Immunological response (20 subjects) from day 1 to day 30 in the following. Cytokines extended including (IL-1β, IL-2, IL-6, IL33 and TNFα) Lymphocyte profile Flowcytometry with identification of monocyte/lymphocyte subsets including but not limited to CD3+/CD4+/CD8+ and CD4+/CD8+ ratio FITMaN panel/Flow cytometry, Interleukins (IL-1β, IL-2, IL-6, IL33 and TNFα), T-reg cells (CD3+/CD4+/CD25+/CD127+) Monocyte proliferation markers, Ex vivo monocyte function

Measure: Immunological response

Time: Through study completion 30 days

Description: Mean change in routine biomarkers for organ dysfunction, from day 1to day 30.

Measure: Multi organ dysfunction

Time: Through study completion 30 days

Description: Viral load, review of records from day 1 to day 30.

Measure: Viral load

Time: Through study completion 30 days

Description: Number of secondary infections, review of records, number of events and patients from day 1 to day 30.

Measure: Secondary infections

Time: Through study completion 30 days

Description: Diagnosed PE needing treatment, review of records, number of events and patients from day 1 to day 30.

Measure: Pulmonary embolism

Time: Through study completion 30 days

Description: Changes on Pulmonary CT, review of records from day 1 to day 30.

Measure: Pulmonary CT

Time: Through study completion 30 days

Description: Changes on Chest X-ray, review of records from day 1 to day 30.

Measure: Chest X-ray

Time: Through study completion 30 days

Description: Changes in Lung ultrasound, review of records from day 1 to day 30.

Measure: Lung ultrasound

Time: Through study completion 30 days
17 Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.

NCT04328467
Conditions
  1. COVID-19
  2. Corona Virus Infection
  3. ARDS
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Hydroxychloroquine
  2. Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.

Measure: COVID-19-free survival

Time: up to 12 weeks

Secondary Outcomes

Description: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

Measure: Incidence of confirmed SARS-CoV-2 detection

Time: up to 12 weeks

Description: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.

Measure: Incidence of possible COVID-19 symptoms

Time: up to 12 weeks

Description: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.

Measure: Incidence of all-cause study medicine discontinuation

Time: up to 12 weeks

Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.

Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end

Time: up to 12 weeks

Description: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

Measure: Incidence of Hospitalization for COVID-19 or death

Time: up to 12 weeks

Description: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.

Measure: Incidence of study medication-related side effects

Time: up to 12 weeks
18 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
19 Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS

Whereas the pandemic due do Covid-19 continues to spread, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Severe Acute Respiratory Distress Syndrome in 30% of patients with a 30%-60% mortality rate for those requiring hospitalization in an intensive care unit. The main physio-pathological hallmark is an acute pulmonary inflammation. Currently, there is no treatment. Mesenchymal stem cells (MSC) feature several attractive characteristics: ease of procurement, high proliferation potential, capacity to home to inflammatory sites, anti-inflammatory, anti-fibrotic and immunomodulatory properties. If all MSC share several characteristics regardless of the tissue source, the highest productions of bioactive molecules and the strongest immunomodulatory properties are yielded by those from the Wharton's jelly of the umbilical cord. An additional advantage is that they can be scaled-up to generate banks of cryofrozen and thus readily available products. These cells have already been tested in several clinical trials with an excellent safety record. The objective of this project is to treat intubated-ventilated patients presenting with a SARS-CoV2-related Acute Respiratory Distress Syndrome (ARDS) of less than 96 hours by three intravenous infusions of umbilical cord Wharton's jelly-derived mesenchymal stromal cells (UC-MSC) one every other day (duration of the treatment: one week). The primary endpoint is the PaO2/FiO2 ratio at day 7. The evolution of several inflammatory markers, T regulatory lymphocytes and donor-specific antibodies will also be monitored. The trial will include 40 patients, of whom 20 will be cell-treated while the remaining 20 patients will be injected with a placebo solution in addition to the standard of care. Given the pathophysiology of SARS-CoV2, it is thus sound to hypothesize that the intravenous administration of UC-MSC during the initial phase of ARDS could control inflammation, accelerate its recovery with improved oxygenation, reduced mechanical ventilation and ventilation weaning time and therefore reduced length of stay in intensive care. The feasibility of the project is supported by the expertise of the Meary Cell and Gene Therapy Center, which is approved for the production of Advanced Therapy Medicinal Products and has already successfully prepared the first batches of cells, as well as by the involvement of a cardiac surgery team which will leverage its experience with stem cells for the treatment of heart failure to make it relevant to the Stroma-Cov-2 project.

NCT04333368
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. Severe Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Umbilical cord Wharton's jelly-derived human
  2. Other: NaCl 0.9%
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Respiratory efficacy evaluated by the increase in PaO2/FiO2 ratio from baseline to day 7 in the experimental group compared with the placebo group

Time: From baseline to day 7

Secondary Outcomes

Measure: Lung injury score

Time: From baseline to day 28

Measure: Oxygenation index

Time: From baseline to day 28

Measure: In-hospital mortality

Time: From baseline to day 28

Measure: Mortality

Time: At day 28

Measure: Ventilator-free days

Time: From baseline to day 28

Measure: Number of days between randomization and the first day the patient meets weaning criteria o Number of days between randomization and the first day the patient meets PaO2/FiO2 > 200 (out of a prone positioning session)

Time: From baseline to day 28

Measure: Cumulative use of sedatives

Time: From baseline to day 28

Measure: Cumulative duration of use of sedatives

Time: From baseline to day 28

Measure: Cumulative duration of use of neuromuscular blocking agents (other than used for intubation)

Time: From baseline to day 28

Measure: Cumulative use of neuromuscular blocking agents (other than used for intubation)

Time: From baseline to day 28

Measure: ICU-acquired weakness and delirium

Time: From baseline to day 28

Measure: Treatment-induced toxicity rate and adverse events up to day 28

Time: From baseline to day 28

Measure: Quality of life at one year (EQ5D-3L quality of life questionnaire)

Time: At 6 months and 12 months

Measure: Measurements of plasmatic cytokines (IL1, IL6, IL8, TNF-alpha, IL10, TGF-beta, sRAGE, Ang2) level

Time: At day 1, 3, 5, 7 and 14

Measure: Anti-HLA antibodies plasmatic dosage

Time: From baseline to day 14, and at 6 months
20 Lipid Ibuprofen Versus Standard of Care for Acute Hypoxemic Respiratory Failure Due to COVID-19: a Multicentre, Randomised, Controlled Trial

The study aims to evaluate the reduction in severity and progression of lung injury with three doses of lipid ibuprofen in patients with SARS-CoV-2 infections.

NCT04334629
Conditions
  1. Coronavirus
  2. Respiratory Distress Syndrome
  3. SARS-CoV Infection
Interventions
  1. Drug: Ibuprofen
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Worsening respiratory failure; defined using severity of hypoxaemia using [PaO2/FiO2 ratio OR SpO2/FiO2 ratio]

Measure: Disease progression

Time: 14 days

Description: Time to mechanical ventilation (or need of)

Measure: Time to mechanical ventilation

Time: 14 days

Secondary Outcomes

Measure: Overall survival

Time: 28 days

Measure: Reduction in proportion of patients who require ventilation

Time: 28 days

Measure: Reduction in length of Critical Care stay

Time: 28 days

Measure: Reduction in length of Hospital stay

Time: 28 days

Measure: Modulation of serum pro- and anti-inflammatory cytokines

Time: 28 days

Measure: Reduction in duration of ventilation

Time: 28 days

Measure: Increase in ventilator-free days

Time: 28 days
21 PRAETORIAN-COVID: A Double-blind, Placebo-controlled Randomized Clinical Trial With Valsartan for PRevention of Acute rEspiraTORy dIstress Syndrome in hospitAlized patieNts With SARS-COV-2 (COVID-19) Infection Disease

Rationale: The current SARS-CoV-2 pandemic has a high burden of morbidity and mortality due to development of the so-called acute respiratory distress syndrome (ARDS). The renin-angiotensin-system (RAS) plays an important role in the development of ARDS. ACE2 is one of the enzymes involved in the RAS cascade. Virus spike protein binds to ACE2 to form a complex suitable for cellular internalization. The downregulation of ACE2 results in the excessive accumulation of angiotensin II, and it has been demonstrated that the stimulation of the angiotensin II type 1a receptor (AT1R) increases pulmonary vascular permeability, explaining the increased lung pathology when activity of ACE2 is decreased. Currently available AT1R blockers (ARBs) such as valsartan, have the potential to block this pathological process mediated by angiotensin II. There are presently two complementary mechanisms suggested: 1) ARBs block the excessive angiotensin-mediated AT1R activation, and 2) they upregulate ACE2, which reduces angiotensin II concentrations and increases the production of the protective vasodilator angiotensin 1-7. In light of the above, ARBs may prevent the development of ARDS and avert morbidity (admission to intensive care unit (ICU) and mechanical ventilation) and mortality. Objective: To investigate the effect of the ARB valsartan in comparison to placebo on the occurrence of one of the following items, within 14 days of randomization:1) ICU admission; 2) Mechanical ventilation; 3) Death. Study design: A double-blind, placebo-controlled 1:1 randomized clinical trial Study population: Adult hospitalized SARS-CoV-2-infected patients (n=651). Intervention: The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160mg b.i.d. and the placebo arm will receive a matching placebo also titrated to blood pressure. Treatment duration will be 14 days or up to hospital discharge < 14 days or occurrence of the primary endpoint if < 14 days. Main study endpoint: The primary study endpoint is the occurrence within 14 days of randomization of either: 1) ICU admission; 2) Mechanical ventilation; 3) Death.

NCT04335786
Conditions
  1. Acute Respiratory Distress Syndrome
  2. SARS-CoV-2
  3. CO
  4. COVID
  5. COVID-19
  6. Severe Acute Respiratory Syndrome
Interventions
  1. Drug: Valsartan (Diovan)
  2. Drug: Placebo oral tablet
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Death is defined as all-cause mortality

Measure: first occurrence of intensive care unit admission, mechanical ventilation or death

Time: within 14 days

Secondary Outcomes

Description: All-cause mortality; and time to all-cause mortality

Measure: Death

Time: Within 14 days, 30 days, 90 days and at 1 year

Description: Occurrence of mechanical ventilation and time to ventilation

Measure: Mechanical ventilation

Time: within 14 days

Description: Occurrence of ICU admission and time to admission

Measure: Intensive care unit admission

Time: within 14 days

Description: Defined as a 50% decline in estimated glomerular filtration rate relative to baseline, or decrease of >30 ml/min/1.73m2 and to a value below 60 ml/min/1.73m2

Measure: Occurrence of acute kidney injury

Time: Within 14 days
22 Impact of Previous Treatment With Angiotensin II Receptor Blockers in Patients With SARS-Cov2 Infection Admitted to the Intensive Care Unit on Survival and Severity of the Disease (COVID-ARA2)

The actual pandemic infection related to SARS-CoV2 results in viral pneumonitis (COVID-19), that may, in the more severe cases, lead the patients to the intensive care unit (ICU). The more frequent presentation is acute respiratory distress syndrome (ARDS). To penetrate cells, SARS-CoV2 uses Angioconvertase type 2 (ACE2) as a cellular entry receptor. ACE2 belong to the renin-angiotensin-aldosteron system (SRAA), and ACE2 levels are directly modified when SRAA inhibitors are administred to patients, and ACE2 level increases particularely with Angiotensin II Receptor blockers (ARA2) use. The aim of our study is to determine ACE2 level and activity in patients with SARSCoV2 infection admitted to the intensive care unit (ICU). COVID ARA2 is a propsective cohort of patient with blood sampling at the day of admission, day 3 and day 7.

NCT04337190
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: blood sampling
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: ELISA test (Higher the ACE2 level, higher the virus penetrate cells)

Measure: ACE2 level change over time

Time: at the day of admission, day 3 and day 7

Secondary Outcomes

Description: Ratio angiotensin (1-7)/angiotensin(1/10) (Higher Ratio angiotensin (1-7)/angiotensin(1/10), higher is ACE2 activity)

Measure: ACE2 activity over time

Time: at the day of admission, day 3 and day 7

Description: Mortality at day 28

Measure: Mortality at day 28

Time: day 28

Description: PaO2/FiO2 ratio (ARDS is severe when <100, moderate when between 100 and 200, mild when >200)

Measure: ARDS severity

Time: from the day of admission to day 7

Description: Day under mechanical ventilation

Measure: Duration of mechanical ventilation

Time: from the day of admission to day 28

Description: Need for prone positionning

Measure: Need for prone positionning

Time: from the day of admission to day 28

Description: Need for extracorporeal membran oxygenation

Measure: Need for extracorporeal membran oxygenation

Time: from the day of admission to day 28

Description: Need for use of paralytic agents

Measure: Use of paralytic agents

Time: from the day of admission to day 28

Description: Need for renal replacement therapy

Measure: Need for renal replacement therapy

Time: from the day of admission to day 28

Description: Need for vasoactive drugs

Measure: Need for vasoactive drugs (norepinephrine, dobutamine,epinephrine)

Time: from the day of admission to day 28

Description: The SOFA score evaluates the severity of patients through 6 items: respiration (PaO2/FiO2 ratio); coagulation (platelets count); liver (bilirubin); Cardiovascular (hypotension); Central nervous system (coma glasgow score) and Renal (creatinine serum level). Score ranges from 0 to 24, a higher score indicates higher severity and probability of death

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: from the day of admission to day 7

Description: Number of session(s) of prone positionning

Measure: Number of session(s) of prone positionning

Time: from the day of admission to day 28

Description: Duration of extracorporeal membran oxygenation treatment

Measure: Duration of extracorporeal membran oxygenation treatment

Time: from the day of admission to day 28

Description: Several vasoactive agents may be used: norepinephrine, dobutamine, epinephrine, vasopressin analogues...

Measure: Type of vasoactive drugs

Time: from the day of admission to day 28

Description: Duration of vasoactive treatment

Measure: Duration of vasoactive treatment

Time: from the day of admission to day 28
23 Hemodynamic Characteristics of Patients With SARS-CoV-2: PiCCOVID Study

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a public health emergency of international concern. Hospitalized COVID-19-positive patients requiring ICU care is increasing along with the course of epidemic. A large number of these patients developed acute respiratory distress syndrome (ARDS) according to current data. However, the related hemodynamic characteristic has so far been rarely described.

NCT04337983
Conditions
  1. Coronavirus
  2. SARS-CoV-2
  3. COVID-19
  4. Acute Respiratory Distress Syndrome
  5. Shock
  6. Acute Circulatory Failure
  7. Left Ventricular Dysfunction
  8. Fluid Overload
Interventions
  1. Device: Transpulmonary thermodilution
  2. Device: Echocardiography
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Ventricular Dysfunction Ventricular Dysfunction, Left Shock

Primary Outcomes

Description: Body temperature(°C)

Measure: Body temperature

Time: Through study completion, an estimation of 6 months

Description: Blood pressure in mmHg

Measure: Blood pressure

Time: Through study completion, an estimation of 6 months

Description: Pulse (heart rate) in times/minute

Measure: Pulse (heart rate)

Time: Through study completion, an estimation of 6 months

Description: Respiratory rate in times/minute

Measure: Respiratory rate

Time: Through study completion, an estimation of 6 months

Description: Cardiac index (L/min/m2)

Measure: Data provided by transpulmonary thermodilution-CI

Time: Through study completion, an estimation of 6 months

Description: Global end-diastolic volume(mL/m2)

Measure: Data provided by transpulmonary thermodilution-GEDV

Time: Through study completion, an estimation of 6 months

Description: Extravascular lung water (mL/kg)

Measure: Data provided by transpulmonary thermodilution-EVLW

Time: Through study completion, an estimation of 6 months

Description: Pulmonary vascular permeability index

Measure: Data provided by transpulmonary thermodilution-PVPI

Time: Through study completion, an estimation of 6 months

Measure: Incidence of abnormal laboratory test results

Time: Through study completion, an estimation of 6 months

Secondary Outcomes

Description: Left ventricle ejection fraction, Segmental left ventricle contractility, Speckle tracking data of the left and right ventricles, Dimensions of right and left cavities and Diastolic function of left ventricle

Measure: Incidence of new-onset or reversible systolic left ventricular dysfunction

Time: Through study completion, an estimation of 6 months

Description: The worst extravascular lung water

Measure: Changes of extravascular lung water measured by transpulmonary thermodilution

Time: Change from baseline extravascular lung water at 6 months

Description: The worst pulmonary vascular permeability index

Measure: Changes of pulmonary vascular permeability index measured by transpulmonary thermodilution

Time: Change from baseline extravascular lung water at 6 months

Measure: Correlation between the hemodynamic characteristics and 90-day mortality

Time: Up to 90th day after inclusion
24 Early Versus Late ECMO Therapy in COVID-19 Induced ARDS (ECMO-VID)

Experimental intervention: Insertion of Extracorporal Membrane Oxygenation (ECMO) within 24 hours of referral to an Intensive Care Unit. Control intervention: Insertion of Extracorporal Membrane Oxygenation (ECMO) as rescue therapy following failure of conventional therapy for ARDS. This conventional therapy will be standardized to reduce bias. Duration of intervention per patient: varies, depending on severity of pulmonary compromise Follow-up per patient: Until hospital discharge Accompanying measures: Serum Samples and bronchoscopy samples of patients included into the trial for secondary analysis of inflammatory parameters and potential biomarkers

NCT04341285
Conditions
  1. ARDS, Human
  2. COVID-19
Interventions
  1. Procedure: ECMO Implantation
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: survival in 28-day follow-up period (28 day all cause mortality)

Measure: 28 day all cause mortality

Time: 28 Days

Secondary Outcomes

Description: 90 day all cause mortality

Measure: 90 day all cause mortality

Time: 90 days

Description: Sepsis-related organ failure assessment score at day 1-14, 28 and 90 days

Measure: Sepsis-related organ failure assessment score at day 1-14, 28 and 90 days

Time: day 1-14, 28 and 90

Description: duration of mechanical ventilation support

Measure: duration of mechanical ventilation support

Time: 28 days

Description: Number of patients with Ventilator Associated Pneumonia

Measure: Ventilator Associated Pneumonia

Time: 28 days

Description: number of blood transfusion units

Measure: Bleeding complications

Time: 28 das

Description: Days on real replacement therapy

Measure: Acute Renal Failure

Time: 28 days

Description: Discharge to (home, skilled nursing facility, rehabilitation)

Measure: Discharge Location

Time: 90 days
25 STUDY ECMO-COVID-19 : Place of ECMO in the Management of Severe Refractory ARDS Associated With Covid-19

Describe COVID-19 patients who are receiving ECMO-VV respiratory replacement and what happens to them.

NCT04343404
Conditions
  1. Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult

Primary Outcomes

Measure: Retrospective description of COVID-19 patients receiving respiratory ECMO-VV supplementation and what happens to them

Time: Files analysed retrospectily from March 1st, 2020 to April 15, 2020 will be examined
26 SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

This study will the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

NCT04344184
Conditions
  1. COVID-19
  2. Lung Injury, Acute
  3. Kidney Injury
Interventions
  1. Drug: L-ascorbic acid
  2. Other: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: COVID disease status will be measured by the 9-point (from 0 to 8) World Health Organization (WHO) ordinal scale for disease improvement at 28 days.

Measure: Change in COVID disease status

Time: Baseline to 28, 60 and 90 days

Secondary Outcomes

Description: Change in serum oxalate levels

Measure: Renal safety biomarkers - serum oxalate

Time: On days 5,7 and 14

Description: Microscopic analysis of urine for presence of oxalate stones

Measure: Renal safety biomarkers - urine oxalate stones

Time: On days 5,7 and 14

Description: 24-hour urine oxalate levels

Measure: Renal safety biomarkers - 24-hour urine oxalate levels

Time: On days 5,7 and 14

Description: Renal-failure free days, with AKI defined by the KDIGO criteria

Measure: Acute Kidney Injury-free days

Time: On day 28, 90

Description: Mortality by all causes

Measure: Number of deaths

Time: On day 28, 60 and 90 days

Description: Difference in plasma ferritin levels in ng/mL, compared to baseline levels

Measure: Change in plasma ferritin levels

Time: Days 1-7 compared with baseline

Description: Difference in D-dimer levels in mcg/mL, compared to baseline levels

Measure: Change in plasma D-dimer levels

Time: Days 1-7 compared with baseline

Description: Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels

Measure: Change in serum lactate dehydrogenase (LDH) levels

Time: Days 1-7 compared with baseline

Description: Difference in plasma IL-6 levels in pg/mL, compared to baseline levels

Measure: Change in plasma IL-6 levels

Time: Days 1-7 compared with baseline

Description: Respiratory failure defined as resource utilization requiring at least 1 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 patients alive and free of respiratory failure

Time: At 28-days

Description: Percentage of patients alive and not requiring invasive mechanical ventilation

Measure: Proportion of patients alive and free of invasive mechanical ventilation

Time: At 28-days
27 Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID19-Induced ARDS: A Randomized, Controlled Study

This is a study for patients who have respiratory infection caused by SARS-CoV-2 that have not gotten better. Because there is no standard treatment for this infection, patients are being asked to volunteer for a gene transfer research study using mesenchymal stem cells (MSCs). Stem cells are cells that do not yet have a specific function in the body. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown from bone marrow (the spongy tissue inside of bones). Stem cells can develop into other types of more mature (specific) cells, such as blood and muscle cells. The purpose of this study is to see if MSCs versus controls can help to treat respiratory infections caused by SARS-CoV-2.

NCT04345601
Conditions
  1. Sars-CoV2
  2. Acute Respiratory Distress Syndrome
  3. COVID-19
Interventions
  1. Biological: Mesenchymal Stromal Cells
  2. Other: Supportive Care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Treatment-related serious adverse events (tSAE) will be considered as those directly related to the investigational infusion product per protocol defined criteria.

Measure: Treatment-related serious adverse events (tSAEs)

Time: 28 days post cell infusion

Description: Change by at least two categories on a six category ordinal scale at day 14 post randomization per protocol defined criteria. The six-category ordinal scale ranges from 6 to 1 with a higher score indicates worse clinical outcome

Measure: Change in clinical status at day 14

Time: 14 days post cell infusion
28 The Effect of Spironolactone on Oxygenation in Covid-19 ARDS Patients

This study intended to evaluate the effects of commonly used diuretic, spironolactone, on oxygenation in covid-19 ARDS patients.

NCT04345887
Conditions
  1. Respiratory Distress Syndrome, Adult
Interventions
  1. Drug: Spironolactone 100mg
  2. Drug: Placebo oral tablet
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: improvement in oxygenation

Measure: p/f ratio

Time: 5 days

Secondary Outcomes

Description: improvement in SOFA Score

Measure: SOFA

Time: 5 days
29 Compassionate Use Open-Label Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)

This protocol proposes to use IC14, a recombinant chimeric monoclonal antibody (mAb) recognizing human CD14, to block CD14-mediated cellular activation in patients early in the development of ARDS. The binding of IC14 to human CD14 prevents CD14 from participating in the recognition of PAMPs and DAMPs due to SARS-CoV-2 infection. The putative mechanism of action of IC14 in ARDS is blockade of PAMP and DAMP interactions with CD14, thus attenuating the inflammatory cascade that leads to increased endothelial and epithelial permeability and injury resulting in alveolar injury and fluid accumulation characteristic of ARDS. IC14 is a chimeric monoclonal antibody that binds to CD14 with high affinity and inhibits signaling via membrane and soluble CD14. Blocking CD14 with IC14 treatment in normal volunteers strongly inhibits systemic inflammation in response to bacterial endotoxin (LPS). University of Washington conducted a small NIH-funded pilot trial of IC14 treatment in 13 patients with ARDS, which suggested that IC14 treatment reduced alveolar inflammation and decreased BAL cytokines. IC14 was also the subject of IND 105803 for a phase 2 study of ARDS from all causes which we propose to revise for the COVID-19 indication. A dosing regimen for IC14 with favorable pharmacokinetics supporting once daily intravenous dosing has been defined, making this an acceptable treatment for hospitalized patients. Two pharmacodynamic biomarkers can be used that are related to CD14, measurements of sCD14 (serum at baseline; urine at baseline and follow up) as well as a CD14 fragment (sCD14-ST; presepsin). A CD14 target engagement assay is available. Therefore, because of the central role of CD14 in the amplification of lung inflammatory responses leading to severe lung injury and the safety record of IC14 in humans, we propose to have an open-label protocol to test the safety and potential efficacy of IC14 treatment in preventing the progression of severe respiratory disease in patients hospitalized with COVID-19.

NCT04346277
Conditions
  1. COVID
  2. ARDS, Human
  3. Ards
  4. SARS-CoV2
Interventions
  1. Biological: IC14, a monoclonal antibody against CD14
MeSH:Respiratory Distress Syndrome, Adult

30 Awake Prone Positioning to Reduce Invasive VEntilation in COVID-19 Induced Acute Respiratory failurE

Prone positioning (PP) is an effective first-line intervention to treat moderate-severe acute respiratory distress syndrome (ARDS) patients receiving invasive mechanical ventilation, as it improves gas exchanges and lowers mortality.The use of PP in awake self-ventilating patients with (e.g. COVID-19 induced) ARDS could improve gas exchange and reduce the need for invasive mechanical ventilation, but has not been studied outside of case series.The investigators will conduct a randomized controlled study of patients with COVID-19 induced respiratory failure to determine if prone positioning reduces the need for mechanical ventilation compared to standard management.

NCT04347941
Conditions
  1. ARDS, Human
  2. Mechanical Ventilation Complication
  3. COVID19
Interventions
  1. Procedure: Prone Positioning
  2. Procedure: Standard of care.
MeSH:Respiratory Insufficiency Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: A measure of effect of awake prone positioning in reducing requirement for invasive mechanical ventilation.

Measure: The effect of prone positioning on requirement for invasive mechanical ventilation in patients with COVID 19 induced respiratory failure.

Time: Up to 28 days post randomisation

Secondary Outcomes

Description: Total time spent in prone and supine position as recorded by nurse

Measure: Length of time tolerating prone positioning

Time: Daily during intervention up to 28 days post randomisation

Description: Measure of change in oxygenation before intervention

Measure: PaO2/FiO2 measured before prone positioning

Time: Immediately before intervention

Description: Measure of change in oxygenation following intervention

Measure: PaO2/FiO2 ratio after 1 hours of prone positioning

Time: During intervention

Description: Measure of change in oxygenation using pulse oximetry before intervention where ABG not available

Measure: SpO2/FiO2 ratio measured before prone positioning

Time: Immediately before intervention

Description: Measure of change in oxygenation before intervention where ABG not available

Measure: SpO2/FiO2 ratio after 1 hours of prone positioning

Time: During Intervention

Description: Escalation of ventilatory support

Measure: Number requiring increase in ventilatory assistance (CPAP+BIPAP+IMV etc)

Time: Up to 28 days post randomisation

Description: Measure of work of breathing in COVID-19 based on Oxygen Delivery Device, Oxygen Saturation and respiratory rate and accessory muscle use with 0-3 Mild, 4-6 Moderate and 7-10 Severe

Measure: Work of breathing assessment (Respiratory distress scale)

Time: Immediately before and during intervention

Description: Substudy examining use of bioimpedance as a surrogate measure of lung edema following prone positioning

Measure: Changes in bioimpedance measures of lung edema in patients in PP

Time: During intervention

Description: Rescue awake prone positioning in control patients in response to hypoxia

Measure: Use of awake prone positioning as a rescue intervention in control patients

Time: Up to 28 days post randomisation
31 Dexamethasone Combined With Hydroxychloroquine Compared to Hydroxychloroquine Alone for Treatment of Severe Acute Respiratory Distress Syndrome Induced by Coronavirus Disease 19 (COVID-19): a Multicentre, Randomised Controlled Trial

Single blind randomized clinical trial designed to evaluate the efficacy of the combination of hydroxychloroquine and dexamethasone as treatment for severe Acute Respiratory Distress Syndrome (ARDS) related to coronavirus disease 19 (COVID-19). We hypothesize that dexamethasone (20 mg for 5 days followed by 10 mg for 5 days) combined with 600 mg per day dose of hydroxychloroquine for 10 days will reduce the 28-day mortality compared to hydroxychloroquine alone in patients with severe ARDS related COVID-19.

NCT04347980
Conditions
  1. Respiratory Distress Syndrome, Adult
  2. COVID-19
Interventions
  1. Drug: Dexamethasone and Hydroxychloroquine
  2. Drug: Hydroxychloroquine
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Mortality rate evaluated 28 days after randomization

Measure: Day-28 mortality

Time: 28 days after randomization

Secondary Outcomes

Description: Ventilator-free days (VFDs) at 28 days are one of several organ failure-free outcome measures to quantify the efficacy of therapies and interventions. VFDs are typically defined as follows: VFDs = 0 if subject dies within 28 days of mechanical ventilation. VFDs = 28 - x if successfully liberated from ventilation x days after initiation. VFDs = 0 if the subject is mechanically ventilated for >28 days.

Measure: Ventilator-free days

Time: 28 days after randomization

Description: Mortality rate evaluated during Intensive care unit stay

Measure: Intensive Care Unit mortality

Time: Up to 60 days after randomization

Description: Mortality rate evaluated 60 days after randomization

Measure: Day-60 mortality

Time: 60 days after randomization

Description: Number of patients with pneumonia diagnosed during intensive care unit stay

Measure: Nosocomial pneumonia

Time: Up to 60 days after randomization

Description: Number of patients with bacteremia diagnosed during intensive care unit

Measure: Bacteremia

Time: Up to 60 days after randomization

Other Outcomes

Description: Placement of ECMO during intensive care unit stay

Measure: Extra corporeal membrane oxygenation (ECMO)

Time: Up to 60days after randomization

Description: Number of patients who underwent tracheostomy during intensive care unit stay

Measure: Tracheostomy

Time: Up to 60 days after randomization

Description: Number of Prone position session

Measure: Prone Position

Time: Up to 60 days after randomization
32 Two-treatment,Randomized, Controlled, Multicenter Clinical Trial to Assess the Safety and Efficacy of Intravenous Administration of Expanded Allogeneic Adipose Tissue Adult Mesenchymal Stromal Cells in Critically Ill Patients COVID-19

The investigational medicinal product consists of expanded allogeneic mesenchymal stromal cells derived from adipose tissue and administered intravenously. The objective of this project is to evaluate the safety and efficacy of the administration of expanded allogeneic adipose tissue adult mesenchymal stem cells, in patients infected with SARS-COV-2 with COVID-19 type complications.

NCT04348461
Conditions
  1. COVID
  2. Respiratory Distres
  3. Respiratory Distress Syndrome
Interventions
  1. Drug: Allogeneic and expanded adipose tissue-derived mesenchymal stromal cells
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult

Primary Outcomes

Measure: Efficacy of the administration of allogeneic mesenchymal stem cells derived from adipose tissue assessed by Survival Rate)

Time: 28 days

Measure: Safety of the administration of allogeneic mesenchymal stem cells derived from adipose tissue assessed by Adverse Event Rate

Time: 6 months
33 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
34 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

NCT04350580
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Drug: Human immunoglobulin
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero

Measure: Ventilator-free days

Time: 28 days

Secondary Outcomes

Description: Vital status at 28 and 90 days

Measure: Mortality

Time: 28 and 90 days

Description: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score

Measure: Sequential Organ Failure Assessment Score

Time: Days 1, 3, 7, 14, 21 and 28

Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)

Measure: P/F ratio

Time: Days 1, 3, 7, 14, 21 and 28

Description: Measure of lung compliance

Measure: Lung compliance

Time: Days 1, 3, 7, 14, 21 and 28

Description: Severity scoring of lung oedema on the chest radiograph

Measure: Radiological score

Time: Days 1, 3, 7, 14, 21 and 28

Description: Concentration in mg/L

Measure: Biological efficacy endpoints - C-reactive protein

Time: Days 1, 3, 7, 14, 21 and 28

Description: Concentration in microgram/L

Measure: Biological efficacy endpoints - Procalcitonin

Time: Days 1, 3, 7, 14, 21 and 28

Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

Measure: Immunological profile

Time: Up to 28 days

Description: Use of corticosteroids, antiretroviral, chloroquine

Measure: Number of patients using other treatments for COVID-19 related ARDS

Time: Up to 28 days

Description: Diagnosis of deep vein thrombosis or pulmonary embolism through imaging exam (eg ultrasound and CT scan)

Measure: Occurrence of deep vein thrombosis or pulmonary embolism

Time: 28 days

Description: Total time of mechanical ventilation, weaning and use of neuromuscular blockade

Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

Time: 28 days

Description: Divided in 3 stages, with higher severity of kidney injury in higher stages

Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis

Time: 28 days

Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

Measure: Occurrence of adverse event related to immunoglobulins

Time: 28 days

Description: Medical research council sum score on awakening

Measure: Occurrence of critical illness neuromyopathy

Time: Up to 28 days

Description: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling

Measure: Occurrence of ventilator-acquired pneumonia

Time: Up to 28 days
35 Evaluation of Respiratory Mechanics and Lung Recruitment in Patients With SARS-CoV-2 Associated Acute Respiratory Distress Syndrome

The aim of this observationnal study is to describe respiratory mechanics and lung recruitement in patients with SARS-CoV-2 Associated Acute Respiratory Distress Syndrome who underwent invasive ventilation on endotracheal tube, admitted to the medical ICU of Angers university hospital . Statics measurements of respiratory system compliance were performed at 2 differents levels of PEEP (15 cmH2O and 5 cmH2O). The recruited volume is computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O . The recruitment-to-Inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) is used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruiter patients.

NCT04350710
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID
Interventions
  1. Other: PEEP trial
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: no unit

Measure: Recruitment-to Inflation ratio (R/I ratio)

Time: Day 1

Description: no unit

Measure: Recruitment-to Inflation ratio (R/I ratio)

Time: Day 5

Description: no unit

Measure: Recruitment-to Inflation ratio (R/I ratio)

Time: Day 10

Secondary Outcomes

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 1

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 5

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 10

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 1

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 5

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 10

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 1

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 5

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 10

Measure: Oesophagal pressure (cm H2O)

Time: Day 1

Measure: Oesophagal pressure (cm H2O)

Time: Day 5

Measure: Oesophagal pressure (cm H2O)

Time: Day 10

Measure: weight (Kg)

Time: Day 1

Measure: weight (Kg)

Time: Day 5

Measure: weight (Kg)

Time: Day 10

Measure: urine output (mL)

Time: day 1

Measure: urine output (mL)

Time: day 5

Measure: urine output (mL)

Time: day 10

Measure: serum creatinine (Umo/L)

Time: day 1

Measure: serum creatinine (Umo/L)

Time: day 5

Measure: serum creatinine (Umo/L)

Time: day 10

Measure: Mean arterial pressure (mmHg)

Time: day 1

Measure: Mean arterial pressure (mmHg)

Time: day 5

Measure: Mean arterial pressure (mmHg)

Time: day 10

Measure: Peak Pressure (cm H2O)

Time: Day 1

Measure: Peak Pressure (cm H2O)

Time: Day 5

Measure: Peak Pressure (cm H2O)

Time: Day 10

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 1

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 5

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 10

Measure: PEP Set (cm H2O)

Time: Day 1

Measure: PEP Set (cm H2O)

Time: Day 5

Measure: PEP Set (cm H2O)

Time: Day 10

Measure: Height (cm)

Time: Day 1

Measure: Airway pening pressure (cm H2O)

Time: day 1

Measure: Airway pening pressure (cm H2O)

Time: day 5

Measure: Airway pening pressure (cm H2O)

Time: day 10

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 15 cmH2O (mL)

Time: Day 1

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 15 cmH2O (mL)

Time: Day 5

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 15 cmH2O (mL)

Time: Day 10

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 5 cmH2O (mL)

Time: Day 1

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 5 cmH2O (mL)

Time: Day 5

Description: respiratory rate decreased to 10 /min, expired tidal volume displayed by the ventilator is noted

Measure: Expired volume in PEEP setted at 5 cmH2O (mL)

Time: Day 10
36 A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.

NCT04350736
Conditions
  1. Acute Lung Injury (ALI) Associated With COVID-19
  2. Inflammatory Lung Conditions Associated With COVID-19
Interventions
  1. Drug: TD-0903
  2. Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events

Time: Day 1 to Day 8

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events

Time: Day 1 to Day 14

Secondary Outcomes

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC

Time: Day 1 through Day 9

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax

Time: Day 1 through Day 9

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax

Time: Day 1 through Day 9
37 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)

Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

NCT04351243
Conditions
  1. COVID-19
Interventions
  1. Drug: Gimsilumab
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

Primary Outcomes

Measure: Incidence of mortality

Time: Day 43

Secondary Outcomes

Measure: Incidence of subjects who are alive and not on mechanical ventilation

Time: Day 29

Description: Subjects who die will be assigned "0" ventilator-free days

Measure: Number of ventilator-free days

Time: Baseline to Day 29

Measure: Time to hospital discharge

Time: Baseline to Day 43
38 Low-flow Extracorporeal Carbon Dioxide Removal Using a Renal Replacement Therapy Platform for Correction of Hypercapnia in COVID-19-associated Acute Respiratory Distress Syndrome

The study aims to investigate the efficacy of extracorporeal CO2 removal for correction of hypercapnia in coronavirus disease 19 (COVID-19)-associated acute respiratory distress syndrome

NCT04351906
Conditions
  1. ARDS
  2. Hypercapnic Respiratory Failure
  3. AKI
Interventions
  1. Device: ECCO2R
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury

Primary Outcomes

Description: Delta partial pressure of carbon dioxide change during ECCO2R treatment

Measure: Delta change in arterial partial pressure of carbon dioxide during ECCO2R treatment

Time: Up to 72 hours

Secondary Outcomes

Description: Epinephrine and norepinephrine dose, mcg/kg/min

Measure: Change in vasopressor use during ECCO2R

Time: Up to 72 hours

Description: Assessment of changes in tidal volume

Measure: Assessment of changes in tidal volume during ECCO2R

Time: Up to 72 hours

Description: Assessment of changes in pH

Measure: Assessment of changes in pH during ECCO2R

Time: Up to 72 hours

Description: Assessment of changes in Positive End-Expiratory Pressure

Measure: Assessment of changes in Positive End-Expiratory Pressure during ECCO2R

Time: Up to 72 hours

Description: Adverse events directly related to ECCO2R are infection at the catheter site, hemorrhage at the cannulation site, air entry in the circuit.

Measure: Number of participants with adverse events directly related to ECCO2R

Time: Up to 72 hours

Description: Adverse events directly related to ECCO2R are clotting of the circuit.

Measure: Rate of technical adverse events related to ECCO2R

Time: Up to 72 hours

Description: Delta change in delta venous partial pressure of carbon dioxide before and after ECCO2R membrane

Measure: Delta change in venous partial pressure of carbon dioxide before and after ECCO2R membrane

Time: Up to 72 hours
39 Efficacy and Safety of Dornase Alfa Aerosol in ARDS Secondary to SARS-CoV-2 Coronavirus Respiratory Infection - COVID-19

This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alfa is a FDA-approved drug for the treatment of cystic fibrosis, which facilitates mucus clearance by cutting apart neutrophil-derived extracellular double-stranded DNA. This study intends to define the impact of aerosolized intra-tracheal Dornase Alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs. The study will recruit mechanically ventilated patients hospitalized in ICU who have been diagnosed with COVID-19 and meet ARDS criteria. It is a prospective, randomized, controlled, multicentric, open-label clinical trial. The goal is to recruit 100 patients.

NCT04355364
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Dornase Alfa Inhalation Solution [Pulmozyme]
  2. Procedure: standard procedure
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The primary endpoint is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from severe to moderate or from moderate to mild

Measure: Efficacy of intratracheal administration: occurrence of at least one grade improvement

Time: Day 7
40 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

41 Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

NCT04355728
Conditions
  1. Corona Virus Infection
  2. ARDS
  3. ARDS, Human
  4. Acute Respiratory Distress Syndrome
  5. COVID-19
Interventions
  1. Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.
  2. Other: Vehicle + Heparin along with best supportive care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Safety will be defined by the incidence of pre-specified infusion associated adverse events as assessed by treating physician

Measure: Incidence of pre-specified infusion associated adverse events

Time: Day 5

Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Measure: Incidence of Severe Adverse Events

Time: 90 days

Secondary Outcomes

Description: Number of participants that are alive at 90 days post first infusion follow up.

Measure: Survival rate after 90 days post first infusion

Time: 90 days

Description: Number of days participants were off ventilators within up to 28 days of hospitalization

Measure: Ventilator-Free Days

Time: 28 days or hospital discharge, whichever is earlier

Description: Measure the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy).

Measure: Change in Oxygenation Index (OI)

Time: 28 days

Description: Measuring respiratory mechanics in ventilated patients [plateau pressure (Pplat)-positive end-expiratory pressure]

Measure: Plat-PEEP

Time: 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) Scores

Time: 28 days

Description: The SIT is a self-administered 40-item test involving microencapsulated (scratch-and-sniff) odors with a forced-choice design. The test has a total score ranging from 0-40 Follows scoring key for evaluation. The higher score indicates better outcome.

Measure: Small Identification Test (SIT) scores

Time: At baseline, day 18 and day 28.

Description: As assessed via serum blood samples.

Measure: Troponin I levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: C-Reactive Protein levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: D-dimer levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: 25-Hydroxy Vitamin D levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Alloantibodies levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Blood white cell count

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Platelets count

Time: Baseline, 28 days
42 Sevoflurane Sedation in COVID-19 ARDS Patients to Reduce Lung Injury: a Randomized Controlled Trial

The purpose of this trial is to study the effect of initial temporary sevoflurane sedation on mortality and persistent organ dysfunction (POD) in survivors at day 28 after ICU admission in the population of patients suffering from COVID-19 ARDS.

NCT04355962
Conditions
  1. ARDS, Human
  2. Coronavirus
Interventions
  1. Drug: Sevoflurane
  2. Drug: Intravenous drug
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: The effect of sevoflurane application on mortality (rate of patients that does not survive 28 days) and persistent organ dysfunction (rate of patients surviving with a persistent organ failure at day 28) will be assessed. Organ failures are defined as pulmonary failure (necessity of ventilation); cardiovascular failure (need of vasopressors), retail failure (need of renal replacement therapy)

Measure: Composite outcome of death rate (rate of patients that did not survive) and organ failure rate (rate of patients surviving with persistent organ dysfunction) at day 28

Time: 28 days

Secondary Outcomes

Description: The effect of sevoflurane application on the length of stay at ICU will be determined.

Measure: Length of stay ICU

Time: 28 days

Description: The impact of sevoflurane on the course of inflammatory markers will be evaluated (pro-calcitonin, PCT; c-reactive protein, CRP; interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1)

Measure: Plasma Inflammatory markers

Time: 8 days

Description: The effect of sevoflurane application on the length of stay at hospital will be determined.

Measure: Length of stay at hospital

Time: 28 days

Description: Sex-related differences in complications will be assessed

Measure: Sex-related differences in complications

Time: 28 days
43 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
44 Low Dose of IL-2 In Acute Respiratory DistrEss Syndrome Related to COVID-19

The purpose is to demonstrate the efficacy of low-dose interleukin 2 (Ld-IL2) administration in improving clinical course and oxygenation parameters in patients with SARS-CoV2-related ARDS.

NCT04357444
Conditions
  1. COVID 19
Interventions
  1. Drug: 1: ILT101
  2. Drug: 2: Placebo Comparator
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Measure: The PaO2/FiO2 ratio at D11

Time: at Day11

Secondary Outcomes

Measure: Changes in Tregs between Baseline and Day 7 (expressed in %)

Time: at Day0 and Day7

Measure: Number of days alive with oxygen therapy within 28 days

Time: at Day28

Measure: Maximal oxygen rate within 28 days

Time: at Day28

Measure: Number of days alive free of invasive or non-invasive ventilation within 28 days

Time: At Day28

Measure: Number of days alive outside ICU within 28 days

Time: at Day28

Measure: Number of days alive outside hospital within 28 days

Time: at Day28

Measure: Time (in days) from randomization to death

Time: through study completion at day 28

Measure: Mortality rate at D28

Time: at Day28

Measure: Difference between CRP levels at randomization and at Day 7 (or at the time of discharge if occurs before Day 7)

Time: at Day0 and Day7 or at the time of discharge

Measure: Use of antibiotics for respiratory (proved or suspected) infection within 28 days

Time: at Day28

Measure: Number of prone positioning sessions

Time: throughout the follow up period at day 28

Measure: Changes in Tregs during the different visits between baseline and day 28

Time: at Day0, 5, 7, 11, 14 and Day28

Description: To evaluate selected immune and inflammatory markers: Serum concentrations of cytokines and soluble factors related to the immune response and inflammatory processes will be evaluated and compare to baseline by multiplex immunoprofiling to analyse a larger number of molecules including at least IFNα2, IFNγ, IL-1α, IL-1β, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, TNFα, TNFβ, VEGF-A, TGF-beta, S-RAGE, SP-A, SP-D, Angiopoétine 1 and KGF.

Measure: Cytokines analysis on plasma samples at Day 0, 7 and 14

Time: at Day 0, 7 and 14

Measure: Tregs numbers during induction period and throughout the follow up period at day 5, 7, 11, 14 and 28 compared to baseline before the first IL-2 injection.

Time: at Day0, 5, 7, 11, 14 and Day28

Measure: Tregs percentages during induction period and throughout the follow up period at day 5, 7, 11, 14 and 28 compared to baseline before the first IL-2 injection.

Time: at Day0, 5, 7, 11, 14 and Day28

Description: Cellular components will be analysed by flow cytometry covering (i) most of the innate and adaptive immune cells including Tregs, T helper cell subsets including follicular helper cells, B cell subsets, NK cell subsets, (ii) the associated relevant markers of activation/function/differentiation, tissue migration, as well as (iii) unconventional lymphoid cells (NKT/MAIT, innate lymphoid cells), myeloid-derived suppressor cells, classical and non-classical monocytes and dendritic cells (mDC1/2, pDC).

Measure: Deep Immunophenotyping of Cellular components in blood samples at Day 0, 7, and 14

Time: at Day0, 7 and Day14

Measure: T cell repertoire on Treg, after sorting from blood at Day 7 and Day 14 and compared to baseline

Time: at Day0, 7 and Day14

Measure: T cell repertoire on Teff (CD4 and CD8) after sorting from blood at Day 7 and Day 14 and compared to baseline

Time: at Day0, 7 and Day14

Measure: Single cells sequencing will be performed in BAL at Day 7 and Day 14 and compared to baseline.

Time: at Day0, 7 and Day14
45 Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection: A Phase 2a Clinical Trial

The global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators. Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with ARDS will die. ARDS currently has no evidence-based treatments other than low tidal ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently needed. The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving oxygen delivery and reducing an expected mortality in that specific patient cohort from 100% to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator (tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control arm to test the efficacy and safety of IV tPA in improving respiratory function and oxygenation, and consequently, successful extubation, duration of mechanical ventilation and survival.

NCT04357730
Conditions
  1. Severe Acute Respiratory Syndrome
  2. Respiratory Failure
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Alteplase 50 MG [Activase]
  2. Drug: Alteplase 50 MG [Activase]
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

Primary Outcomes

Description: Ideally, the PaO2/FiO2 will be measured with the patient in the same prone/supine position as in baseline, as change in positions may artificially reduce the improvement attributable to the study drug. However, given the pragmatic nature of the trial, the prone/supine position will be determined by the attending physician, in which case, we will use as an outcome the PaO2/FiO2 closest to the 48 hours obtained prior to the change in position as the outcome.

Measure: PaO2/FiO2 improvement from pre-to-post intervention

Time: at 48 hours post randomization

Secondary Outcomes

Description: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2 (whatever is lower)

Measure: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2

Time: at 48 hours post randomization

Description: This score is based on seven clinical features (respiration rate, hypercapnic respiratory failure, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness) and determines the degree of illness of a patient and prompts critical care intervention.

Measure: National Early Warning Score 2 (NEWS2)

Time: at 48 hours post randomization

Description: The ordinal scale is an assessment of the clinical status 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. (combined items 7 and 8 as our study is limited to hospital).

Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale

Time: at 48 hours post randomization

Description: 48 hour mortality for hospitalized patients

Measure: 48 hour in-hospital mortality

Time: at 48 hours post randomization

Description: 14 days mortality for hospitalized patients

Measure: 14 days in-hospital mortality

Time: 14 days post randomization

Description: 28 days mortality for hospitalized patients

Measure: 28 days in-hospital mortality

Time: 28 days post randomization

Description: ICU-free days will be calculated based on (28 - number of days spent in the ICU) formula

Measure: ICU-free days

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)

Description: In-hospital coagulation-related events include bleeding, stroke, myocardial infarction and venous thromboembolism (VTE). In-hospital coagulation-related event-free (arterial and venous) days will be calculated based on (28 - number of days without coagulation-related event) formula.

Measure: In-hospital coagulation-related event-free (arterial and venous) days

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)

Description: Ventilator-free days will be calculated based on (28 - number of days on mechanical ventilation) formula.

Measure: Ventilator-free days

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)

Description: Calculated for patients who was on a mechanical ventilation any period of time during hospitalization. The extubation will be considered successful if no re-intubation occurred for more than 3 days have passed after the initial extubation.

Measure: Successful extubation

Time: Day 4 after initial extubation

Description: Calculated for patients who was on paralytics at the time of randomization. The weaning will be considered successful if no paralytics were used for more than 3 days have passed after termination of paralytics.

Measure: Successful weaning from paralysis

Time: Day 4 after initial termination of paralytics

Description: Is counted for the patients who was alive at the time of discharge.

Measure: Survival to discharge

Time: 28 days of hospital stay or until hospital discharge (whichever comes first)
46 Impact of Dexmedetomidine Infusion on the Time Course and Outcomes of Acute Respiratory Distress Syndrome (ARDS) in Patients Affected by the SARS-CoV-2 (COVID-19) Admitted to Critical Care Unit

A continuous infusion of Dexmedetomidine (DEX) will be administered to 80 patients admitted to Critical Care because of signs of Respiratory Insufficiency requiring non-invasive ventilation. Measurements of respiratory performance and quantification of cellular and molecular inflammatory mediators. The primary outcome will be the avoidance of mechanical ventilation with secondary outcomes duration of mechanical ventilation, avoidance of delirium after sedation and association of mediators of inflammation to outcomes. Outcomes will be compared to a matched historical control (no DEX) series

NCT04358627
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Inflammation
  3. Dexmedetomidine
  4. Cytokine Storm
  5. Delirium, Emergence
Interventions
  1. Drug: Dexmedetomidine Injectable Product
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Delirium Emergence Delirium Syndrome Inflammation

Primary Outcomes

Description: (Presence/Absence) requirement of mechanical ventilation

Measure: Mechanical ventilation

Time: expected within first three days (non conclusive due to lack of evidence yet)

Secondary Outcomes

Description: Duration of mechanical ventilation if it is required (hours from the start)

Measure: Duration of mechanical ventilation

Time: expected within first seven days (non conclusive due to lack of evidence yet)

Description: Delirium criteria as defined in DSM-4

Measure: Delirium on recovery from sedation

Time: First 24 hours after retiring dexmedetomidine sedation
47 Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) induces high mortality, particularly in the context of COVID-19 disease. Preliminary data from patients with ARDS related to COVID-19 disease appear to show significant effectiveness of prone positioning in intubated patients in terms of oxygenation as well as nasal high flow therapy before intubation. It should be noted that in Jiangsu province, secondarily affected, nasal high flow combined with the prone position was successfully integrated into care protocols. The investigators hypothesize that the combined application of nasal high flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for tracheal intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources. Investigators hypothesize that the combined application of nasal high-flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

NCT04358939
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Other: Prone decubitus
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels.

Measure: Therapeutic failure within 14 days of randomization

Time: From randomization to day 14

Secondary Outcomes

Description: Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels.

Measure: Therapeutic failure within 28 days of randomization

Time: From randomization to day 28

Measure: Timeframe of intubation or death

Time: From randomization to day 28

Measure: Timeframe of therapeutic escalation (in case of non-invasive ventilation at two pressure levels)

Time: From randomization to day 28

Measure: Evolution of oxygenation (PaO2/FiO2 ratio or SpO2/FiO2 surrogate) over the 14 days following randomization

Time: From randomization to day 14

Measure: Evolution of the SpO2/FiO2 ratio during the first prone session

Time: From randomization to day 1

Description: ROX index is the ratio of pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate.

Measure: Evolution of the ROX index during the first prone session

Time: From randomization to day 1

Description: Score reaches from 1 to 7, 7 indicates worse outcome

Measure: Evolution of the World Health Organization disease severity score of COVID

Time: From randomization to day 28

Description: Comfort evaluted by the patient through a visual analogical scale

Measure: Patient comfort before, during and after the first prone position session

Time: From randomization to day 1

Measure: Occurrence of skin lesions on the anterior surface of the body

Time: From randomization to day 28

Description: Invasive devices include : central and peripheric vascular catheters, tracheal tube, urinary catheter, chest tubes.

Measure: Displacement of invasive devices during reversals

Time: From randomization to day 28

Measure: Days of nasal High-Flow therapy use in the general population, in non-intubated patients and in intubated patients

Time: From randomization to day 28

Measure: Days spent in the intensive care unit and in the hospital

Time: From randomization to day 28

Measure: Mortality in the intensive care unit and in the hospital

Time: From randomization to day 28

Measure: Ventilator-free-days within 28 days of randomization

Time: From randomization to day 28
48 Avoiding High PEEP in COVID-19 Induced ARDS: a Multi-center Study

This was a multi-center prospective study. All consecutive severe cases of COVID-19 whose PO2/FiO2<300mmHg with invasive ventilation admitted to 5 fixed-point receive COVID-19 patients hospitals in Wuhan from 5 March to 15 March 2020 were included. Epidemiological, clinical data, lung mechanics, artery blood gas test and hemodynamics at three methods to titrate PEEP, optimizing oxygenation, optimizing compliance, ARDSnet. The study was approved by the Ethics Committee of Zhongda Hsopital, Southeast University.

NCT04359251
Conditions
  1. COVID-19
  2. Mechanical Ventilation Pressure High
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Other: Gas exchanges at different PEEP
  2. Other: lung mechanics at different PEEP
  3. Other: Hemodynamics changes at different PEEP
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: the respiratory system compliance was compared among three groups

Measure: Respiratory system compliance improvement

Time: 20 minutes

Secondary Outcomes

Description: P/Fwere compared among three groups

Measure: Gas echanges improvement

Time: 20 minutes

Other Outcomes

Description: MAP were compared among three groups

Measure: hemodynamics improvement

Time: 20 minutes
49 Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS A Single-arm, Open-label, Proof of Concept Study

The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of patients with COVID-19 severe pneumonia.

NCT04359290
Conditions
  1. ARDS, Human
  2. COVID
Interventions
  1. Drug: Ruxolitinib administration
MeSH:Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: To determine the efficacy of ruxolitinib measured by overall survival

Measure: Overall survival

Time: 28 days after registration into trial

Secondary Outcomes

Description: Assessment of the duration of ventilation support

Measure: Assessment of the duration of ventilation support

Time: registration until 90 days after registration into trial

Description: Assessment of the extent of cytokine storm reduction (IL-6, CRP, ferritin)

Measure: cytokine storm

Time: registration until 90 days after registration into trial

Description: To assess time on ICU

Measure: time on ICU

Time: registration until 90 days after registration into trial

Description: In order to classify the severity of the AEs, number of participants with treatment-related adverse events will be assessed by the "Common Terminology Criteria for Adverse Events" (CTCAE) version 5.0

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

Time: registration until 90 days after registration into trial

Description: To assess the timeframe for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG)

Measure: time frame for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG)

Time: registration until 90 days after registration into trial

Description: To asses the rates of flow (liter/minute), in order to detect possible amelioration of pulmonary function after Covid-19 infection

Measure: Rates of flow

Time: Discharge from hospital (end of treatment)

Description: To asses gas exchange (partial pressure of oxygen and carbon dioxide), in order to detect possible amelioration of pulmonary function after Covid-19 infection

Measure: Gas exchange

Time: Discharge from hospital (end of treatment)

Description: To assess forced expiratory volume in 1 second (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

Measure: Forced expiratory volume in 1 second (FEV1)

Time: Discharge from hospital (end of treatment)

Description: To assess forced vital capacity (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

Measure: Forced vital capacity (FVC)

Time: Discharge from hospital (end of treatment)

Description: To assess Tiffeneau-Pinelli index (FEV1/FVC ratio in %), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

Measure: Tiffeneau-Pinelli index

Time: Discharge from hospital (end of treatment)

Description: To determine the efficacy of ruxolitinib measured by overall survival

Measure: Overall survival

Time: 90 days after registration into trial
50 Sedation With Sevoflurane Versus Propofol in Patients With Acute Respiratory Distress Syndrome Caused by COVID19 Infection

It is a multicenter, national, randomized 1:1 ratio, controlled, parallel, open study. Patients with severe ARDS-CoVid19 will be included in the trial within the first 24 hours. Patients will be randomized to one of the treatment groups: - SEV group: 25 patients with Sevoflurane sedation by inhalation, starting at 6 ml/h and changing every 15 minutes until an adequate level of sedation is achieved (BIS 40-50) - PRO group: 25 patients standard sedation with intravenous propofol, starting with 2 mg/kg/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50)

NCT04359862
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID19 Infection
Interventions
  1. Drug: Sevoflurane
  2. Drug: Propofol
MeSH:Infection Communicable Diseases Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: To evaluate the effect of 48-hour treatment with inhaled sevoflurane on arterial oxygenation, assessed by PaO2/FiO2 on day two, in patients with ARDS-CoVid19

Measure: PaO2/FiO2

Time: Day 2

Secondary Outcomes

Description: To quantify the effects of sevoflurane on pro-inflammatory cytokine levels during ARDS-CoVid19

Measure: TNFα

Time: Day 2

Description: To quantify the effects of sevoflurane on pro-inflammatory cytokine levels during ARDS-CoVid19

Measure: IL-1b

Time: Day 2

Description: To quantify the effects of sevoflurane on pro-inflammatory cytokine levels during ARDS-CoVid19

Measure: IL-6

Time: Day 2

Description: To quantify the effects of sevoflurane on pro-inflammatory cytokine levels during ARDS-CoVid19

Measure: IL-8

Time: Day 2

Description: To evaluate the 30-day mortality.

Measure: Mortality

Time: Day 30
51 Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19

Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

NCT04360096
Conditions
  1. SARS-CoV 2
  2. COVID
  3. ARDS
  4. ALI
  5. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  6. Dyspnea
Interventions
  1. Drug: RLF-100 (aviptadil)
  2. Drug: Placebo
  3. Device: Nebulized administration of RLF-100 or Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Sy Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
HPO:Dyspnea Respiratory distress

Primary Outcomes

Description: Progression to ARDS is defined as the need for mechanical ventilation

Measure: Progression to ARDS

Time: 28 days

Secondary Outcomes

Description: Blood PO2 as measured by pulse oximetry

Measure: Blood oxygenation

Time: 28 days

Description: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity

Measure: RDP Dsypnea Scale

Time: 28 days

Description: Distance walked in six minutes

Measure: Distance walked in six minutes

Time: 28 days
52 Pilot Study on Cytokine Filtration in COVID-19 ARDS (CytokCOVID19)

Background: There are no proven therapies for COVID-19 infection. COVID-19 infects the respiratory epithelium of the lower airways, causing widespread damage via cytopathic effects, resulting in severe inflammation and Pneumonitis. High local and circulating levels of cytokines, or cytokine storm, can lead to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS). Methods: This is a pilot randomized, controlled, uni-center study testing safety and efficacy of cytokine filtration on patients with severe ARDS. Eligible patients will be randomized to 72 hours filtration or no filtration on top of the standard treatment for ARDS. Indications for randomization are patients with moderate or severe ARDS with need of ventilation support (either invasive or non-invasive), with inflammatory markers. The primary outcome will be days on mechanical ventilation (MV) support. Secondary outcomes are 30-day mortality, ICU days, need for extracorporeal membrane oxygenation (ECMO) support, duration of renal replacement therapy (RRT) and catecholamine therapies, hospital length of stay, multi-organ failure. All analysis will be done according to the intention to treat principle.

NCT04361526
Conditions
  1. Coronavirus Infection
  2. Acute Respiratory Distress Syndrome
  3. COVID
Interventions
  1. Device: Cytokine Adsorption
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Number of ventilator-free days (VFDs) at day 28 (defined as days being alive and free from mechanical ventilation at day 28 after enrollment. For patients ventilated 28 days or longer and for ventilated subjects who die, VFD is 0

Measure: Mechanical ventilation-free days

Time: up to 28days

Secondary Outcomes

Measure: 30-day mortality

Time: up to 30 days

Measure: length of ICU stay (days)

Time: up to 30 days

Measure: length of hospital stay

Time: up to 30 days

Measure: Duration of renal replacement and cathecolamines therapies

Time: up to 30 days

Measure: Need for extracorporeal membrane oxygenation (ECMO) support

Time: up to 30 days

Measure: multi-organ failure measured by the Sequential Organ Failure Assessment (SOFA) score

Time: up to 30 days (measured on days 0, 1, 2, 3, 4, 5, 6, and the last day of mechanical ventilation)
53 COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study

It is an observational, cohort, retrospective, monocentric, non-profit study. The primary objective is to evaluate the efficacy and safety of ruxolitinib in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours.

NCT04361903
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
Interventions
  1. Drug: Ruxolitinib Oral Tablet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Syndrome

Primary Outcomes

Description: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours

Measure: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19

Time: 15 days

Secondary Outcomes

Description: ABG (arterial Blood Gas): pH as SI Unit, every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pH

Time: 15 days

Description: ABG (arterial Blood Gas): pO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pO2

Time: 15 days

Description: ABG (arterial Blood Gas): pCO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO2

Time: 15 days

Description: PaO2 / FiO2, SatO2 ratio. Vital parameters and respiratory function every 12 hours and in any case in the presence of significant clinical variations.

Measure: Improvement of respiratory performance - ratio values

Time: 15 days

Description: every 24 hours D-Dimer value in mgr/ml

Measure: Evaluation of known adverse events related to the use of the drug - D-Dimer

Time: 15 days

Description: every 24 hours fibrinogen value in mg/dl

Measure: Evaluation of known adverse events related to the use of the drug - fibrinogen

Time: 15 days

Description: every 24 hours transaminases value in U/L

Measure: Evaluation of known adverse events related to the use of the drug - transaminases

Time: 15 days

Description: every 24 hours aPTT value in seconds

Measure: Evaluation of known adverse events related to the use of the drug - aPTT

Time: 15 days

Description: every 24 hours INR value in %

Measure: Evaluation of known adverse events related to the use of the drug - INR

Time: 15 days

Description: every 24 hours glycemia value in mg/dl

Measure: Evaluation of known adverse events related to the use of the drug - glycemia

Time: 15 days

Description: every 24 hours creatinine serum value in mg/dl

Measure: Evaluation of known adverse events related to the use of the drug - creatinine

Time: 15 days

Description: Total leucocyte as CBC x10e)/L

Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes count

Time: 15 days

Description: formula % on total leucocyte

Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes formula

Time: 15 days

Description: Thoracic imaging, every 48 h: presence, extension and dimension on lung thickening - Chest CT at start and end of treatment, Time elapsed between the onset of clinical symptoms and hospitalization.

Measure: Evaluation of the epidemiological parameters: Chest CT

Time: 15 days

Description: Thoracic imaging: every day: presence and number of line B every 48 hours.Time elapsed between the onset of clinical symptoms and hospitalization.

Measure: Evaluation of the epidemiological parameters: Eco Chest

Time: 15 days

Description: Thoracic imaging: presence, extension and dimension on lung thickening - Chest X-ray, Time elapsed between the onset of clinical symptoms and hospitalization.

Measure: Evaluation of the epidemiological parameters: CHEST X-ray

Time: 15 days

Description: Monitoring of serum cytokines (IL-6 in pgr/dL, TNF in pgr/dL) every 48 h

Measure: Monitoring of Serum levels of cytokines before and every 48 h from start to to end of treatment

Time: 15 days

Description: Number of AE grade 1 to 4

Measure: Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy

Time: 15 days
54 Impact of Prone Position in Patients Under Spontaneous Breathing on Intubation or Non-invasive Ventilation or Death Incidence During COVID-19 Acute Respiratory Distress

The SARS-Cov2 viral pandemic is responsible for a new infectious disease called COVID-19 (CoronaVIrus Disease), is a major health problem. Respiratory complications occur in 15 to 40%, the most serious is acute respiratory distress syndrome (ARDS). The management of COVID-19 is essentially symptomatic with respiratory oxygen supplementation in mild forms to invasive mechanical ventilation in the most severe forms. Prone position (PP) reduced mortality in patients with ARDS in intensive care. Ding et al showed that PP and high flow oxygenation reduced the intubation in patients with moderate to severe ARDS. The investigators hypothesize that the use of PP in spontaneously ventilation patients under oxygen standard could decrease incidence of intubation or non-invasive ventilation or death compared to conventional positioning management in medical departments.

NCT04363463
Conditions
  1. COVID19
  2. Oxygen Therapy
  3. Prone Position
  4. Spontaneous Ventilation
  5. Respiratory Distress Syndrome
Interventions
  1. Other: prone position
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: To show that PP in spontaneously ventilation patients could reduce the risk of acquiring the following event (composite endpoint): Endotracheal intubation Or non-invasive ventilation (NIV) with two pressure levels And/or death

Measure: Percent age of patients who will have endotracheal intubation or non-invasive ventilation at two pressure levels and/or die, in each of the 2 randomization groups.

Time: Day 28

Secondary Outcomes

Description: Show that the use of prone position improves the WHO ordinal scale score by 2 points faster (after randomization)

Measure: Duration in days for the change of 2 points on the WHO ordinal scale

Time: Day 28

Description: Show that prone position with spontaneous ventilation reduces the need for endotracheal intubation and invasive mechanical ventilation

Measure: Rate (%) of intubation and invasive ventilation in the 2 randomization groups.

Time: Day 28

Description: Show that prone position with spontaneous ventilation reduces the use of non-invasive ventilation at two pressure levels

Measure: Rate (%) of non-invasive ventilation at two pressure levels in the 2 randomization groups

Time: Day 28

Description: Show that prone position in spontaneous ventilation reduces the time under oxygen therapy.

Measure: Duration of oxygen therapy in the 2 randomization groups.

Time: Day 28

Description: Show that prone position reduces the length of hospitalization.

Measure: Duration of hospitalization in the 2 randomization groups.

Time: Day 28

Description: Compare the hospital mortality of the 2 groups

Measure: Hospital mortality and mortality at D28 in the 2 randomization groups

Time: Day 28

Description: Compare the incidence of the need for resuscitation transfer between the two groups.

Measure: Rate (%) of need for transfer to intensive care unit

Time: Day 28

Description: Compare the impact of the use of non-invasive ventilation and intubation on the entire hospital stay when the hospital stay is longer than 28 days between the two groups.

Measure: Rate (%) of use of non-invasive ventilation at two pressure levels, intubation throughout the entire stay when the stay is longer than 28 days.

Time: 1 year
55 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

NCT04365985
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Severe Acute Respiratory Syndrome (SARS)
  4. Coronavirus Infections
Interventions
  1. Drug: Naltrexone
  2. Drug: Ketamine
  3. Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)

Measure: Progression of oxygenation needs

Time: up to 1 month

Secondary Outcomes

Description: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.

Measure: Renal failure

Time: up to 1 month

Description: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits

Measure: Liver failure

Time: up to 1 month

Description: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)

Measure: Cytokine Storm

Time: up to 1 month

Description: Count of participants who die from COVID-19

Measure: Mortality

Time: up to 1 month post hospital discharge

Description: Length of hospital stay in days

Measure: Length of hospital stay

Time: up to 1 month

Description: Count of patients admitted to the ICU at any time during index hospitalization

Measure: Intensive Care Unit (ICU) admission

Time: up to 1 month

Description: Length of ICU stay in days

Measure: Intensive Care Unit (ICU) duration

Time: up to 1 month

Description: Count of participants requiring intubation

Measure: Intubation

Time: up to 1 month

Description: Length of intubation, measured in days

Measure: Intubation duration

Time: up to 1 month

Description: Time measured in days from hospital admission to determination patient is stable for discharge

Measure: Time until recovery

Time: up to 1 month
56 Mesenchymal Stem Cell Therapy for Acute Respiratory Distress Syndrome in Coronavirus Infection: A Phase 2-3 Clinical Trial

Acute Respiratory Distress Syndrome (ARDS) is the major cause of death in the COVID-19 pandemic. In this trial, the safety and efficacy of Mesenchymal Stem Cells (MSC) for the treatment of ARDS in COVID-19 patients will be assessed.

NCT04366063
Conditions
  1. Covid-19
Interventions
  1. Biological: Cell therapy protocol 1
  2. Biological: Cell therapy protocol 2
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

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

Measure: Adverse events assessment

Time: From baseline to day 28

Description: Evaluation of Pneumonia Improvement

Measure: Blood oxygen saturation

Time: From baseline to day 14

Secondary Outcomes

Description: Number of days

Measure: Intensive care unit-free days

Time: Up to day 8

Description: Improvement of clinical symptoms including duration of fever, respiratory distress, pneumonia, cough, sneezing

Measure: Clinical symptoms

Time: From baseline to day 14

Description: increase in PaO2/FiO2 ratio from baseline to day 7

Measure: Respiratory efficacy

Time: From baseline to day 7

Description: Biochemical examination

Measure: Biomarkers concentrations in plasma

Time: At baseline, 7, 14, 28 days after the first intervention
57 A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study Evaluating AVM0703 in Patients With COVID-19

This is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous (IV) infusion to patients with COVID-19. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single-ascending dosing of AVM0703 in patients with COVID-19.

NCT04366115
Conditions
  1. Covid19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: AVM0703
  2. Drug: Placebo
  3. Drug: hydrocortisone
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The primary endpoint of the Phase 1 portion of the study is to evaluate the safety of AVM0703 in subjects with severe or life-threatening COVID-19 infection, and to identify the RP2D.

Measure: Dose-Limiting Toxicities

Time: 0-12 months

Description: The primary endpoint of the Phase 1/2 portion of the study is to evaluate the efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.

Measure: 28 day all-cause mortality will be a primary end point for Phase 1 and 2

Time: 0-12 months
58 Intermediate-size Expanded Access of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells for Acute Respiratory Distress Syndrome Due to COVID-19 Infection

The objectives of this intermediate-size expanded access protocol are to assess the safety and efficacy of remestemcel-L in participants with ARDS due to coronavirus infection 2019 (COVID-19).

NCT04366830
Conditions
  1. Moderate to Severe Acute Respiratory Distress Syndrome Associated With COVID-19
Interventions
  1. Drug: Remestemcel-L
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

59 European/Euro-ELSO Survey on Adult and Neonatal/ Pediatric COVID Patients in ECMO

In the last 10 years, severe acute respiratory infection (SARI) was responsible of multiple outbreaks putting a strain on the public health worldwide. Indeed, SARI had a relevant role in the development of pandemic and epidemic with terrible consequences such as the 2009 H1N1 pandemic which led to more than 200.000 respiratory deaths globally. In late December 2019, in Wuhan, Hubei, China, a new respiratory syndrome emerged with clinical signs of viral pneumonia and person-to-person transmission. Tests showed the appearance of a novel coronavirus, namely the 2019 novel coronavirus (COVID-19). Two other strains, the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have caused severe respiratory illnesses, sometimes fatal. In particular, the mortality rate associated with SARS-CoV and MERS-CoV, was of 10% and 37% respectively. Even though COVID-19 appeared from the first time in China, quickly it spread worldwide and cases have been described in other countries such as Thailand, Japan, South Korea, Germany, Italy, France, Iran, USA and many other countries. An early paper reported 41 patients with laboratory-confirmed COVID-19 infection in Wuhan. The median age of the patients was 49 years and mostly men (73%). Among those, 32% were admitted to the ICU because of the severe hypoxemia. The most associated comorbidities were diabetes (20%), hypertension (15%), and cardiovascular diseases (15%). On admission, 98% of the patients had bilateral multiple lobular and sub-segmental areas of consolidation. Importantly, acute respiratory distress syndrome (ARDS) developed in 29% of the patients, while acute cardiac injury in 12%, and secondary infection in 10%. Invasive mechanical ventilation was required in 10% of those patients, and two of these patients (5%) had refractory hypoxemia and received extracorporeal membrane oxygenation (ECMO). In a later retrospective report by Wang and collaborators, clinical characteristics of 138 patients with COVID-19 infection were described. ICU admission was required in 26.1% of the patients for acute respiratory distress syndrome (61.1%), arrhythmia (44.4%), and shock (30.6%). ECMO support was needed in 11% of the patients admitted to the ICU. During the period of follow-up, overall mortality was 4.3%. The use of ECMO in COVID-19 infection is increasing due to the high transmission rate of the infection and the respiratory-related mortality. Therefore, the investigators believe that ECMO in case of severe interstitial pneumonia caused by COVID could represent a valid solution in order to avoid lung injuries related to prolonged treatment with non-invasive and invasive mechanical ventilation. In addition, ECMO could have a role for the systemic complications such as septic and cardiogenic shock as well myocarditis scenarios. Potential clinical effects and outcomes of the ECMO support in the novel coronavirus pandemic will be recorded and analyzed in our project. The researchers hypothesize that a significant percentage of patients with COVID-19 infection will require the utilize of ECMO for refactory hypoxemia, cardiogenic shock or septic shock. This study seeks to prove this hypothesis by conducting an observational retrospective/prospective study of patients in the ICU who underwent ECMO support and describe clinical features, severity of pulmonary dysfunction and risk factors of COVID-patients who need ECMO support, the incidence of ECMO use, ECMO technical characteristics, duration of ECMO, complications and outcomes of COVID-patients requiring ECMO support.

NCT04366921
Conditions
  1. COVID
  2. SARS-CoV-2
  3. ARDS, Human
  4. Refractory Hypoxemia
  5. Cardiogenic Shock
  6. Septic Shock
  7. Extracorporeal Membrane Oxygenation
MeSH:Respiratory Distress Syndrome, Adult Shock, Cardiogenic Shock Hypoxia
HPO:Cardiogenic shock Hypoxemia

Primary Outcomes

Description: age in years

Measure: Age

Time: at baseline

Description: male/female

Measure: Gender

Time: at baseline

Description: in kilograms

Measure: Weight

Time: at baseline

Description: in meters

Measure: Height

Time: at baseline

Description: weight and height combined to calculate BMI in kg/m^2

Measure: BMI

Time: at baseline

Description: Asthma y/n, cystic fibrosis y/n, chronic obstructive pulmonary disease y/n, pulmonary hypertension y/n, pulmonary fibrosis y/n, chronic restrictive lung disease y/n

Measure: Pre-existing pulmonary disease y/n

Time: at baseline

Description: diabetes mellitus y/n, chronic renal failure y/n, ischemic heart disease y/n, heart failure y/n, chronic liver failure y/n, neurological impairment y/n

Measure: Main co-morbidities y/n

Time: at baseline

Description: in dd-mm-yyyy or mm-dd-yyyy

Measure: Date of signs of COVID-19 infection

Time: at baseline or date of occurence

Description: in dd-mm-yyyy or mm-dd-yyyy

Measure: Date of positive swab

Time: at baseline or date of occurence

Description: in days

Measure: Pre-ECMO length of hospital stay

Time: at or during ECMO-implant

Description: in days

Measure: Pre-ECMO length of ICU stay

Time: at or during ECMO-implant

Description: in days

Measure: Pre-ECMO length of mechanical ventilation days

Time: at or during ECMO-implant

Description: y/n, what kind

Measure: Use of antibiotics

Time: up to 6 months

Description: y/n, what kind

Measure: Use of anti-viral treatment

Time: up to 6 months

Description: y/n, what kind (eg prone-position, recruitment manoeuvers, neuromuscular blockade etc)

Measure: Use of second line treatment

Time: up to 6 months

Description: respiratory or cardiac

Measure: Indications for ECMO-implant

Time: at ECMO-implant

Description: veno-venous, veno-arterial or veno-venoarterial

Measure: Type of ECMO-implant

Time: at ECMO-implant

Description: peripheral or central

Measure: Type of access

Time: at ECMO-implant

Description: in dd-mm-yyyy or mm-dd-yyyy

Measure: Date of ECMO implant

Time: at ECMO-implant

Description: l/min

Measure: ECMO blood flow rate

Time: from day of ECMO-implant for every 24 hours until date of weaning or death, up to 6 months

Description: l/min

Measure: ECMO gas flow rate

Time: from day of ECMO-implant for every 24 hours until date of weaning or death, up to 6 months

Description: y/n

Measure: ECMO configuration change

Time: up to 6 months

Description: in dd-mm-yyyy or mm-dd-yyyy

Measure: Date of ECMO configuration change

Time: up to 6 months

Description: veno-venous, veno-arterial, veno-venoarterial, other

Measure: New ECMO configuration

Time: up to 6 months

Description: right ventricular failure, left ventricular failure, refractory hypoxemia

Measure: Indications for ECMO configuration change

Time: up to 6 months

Description: settings of ventilator

Measure: Ventilator setting on ECMO

Time: from day of ECMO-implant for every 24 hours until date of weaning or death, up to 6 months

Description: heparin, bivalirudin, nothing

Measure: Anticoagulation during ECMO

Time: from day of ECMO-implant for every 24 hours until date of weaning or death, up to 6 months

Description: amount of ECMO circuit changes (1, 2, 3 etc.)

Measure: Frequency of ECMO circuit change

Time: up to 6 months

Description: Hemorrhagic, infection, other complications

Measure: ECMO complications

Time: up to 6 months

Description: y/n

Measure: ECMO Weaning

Time: from day of ECMO-implant for every 24 hours until date of weaning or death, up to 6 months

Description: y/n, date

Measure: ICU discharge

Time: from day of ICU-admission for every 24 hours until date of discharge or death, up to 6 months

Measure: Main cause of death

Time: 6 months

Description: Ward, another ICU, rehabilitation center, home

Measure: Type of discharge

Time: up to 6 months

Measure: Alive/deceased

Time: 6 months
60 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
61 Trans Thoracic Manipulation of Ventilation/Perfusion: the V/Q Vest

The objective of this research is optimizing oxygenation in patients in the setting of acute hypoxic respiratory failure in relation to corona virus disease 2019 (COVID-19) through non-invasive manipulation as a complementary therapy to traditional advanced mechanical ventilator support, or as a marker of responsivity to supportive therapies. The intent is to determine if it is possible to physically improve the ability of the lungs to take up oxygen by applying external pressure to the chest. It is hypothesized that the use of the vest for this patient population will alter the blood flow through the lungs and thereby improve oxygen levels in the body. Participants will wear the ventilation/perfusion (V/Q) vest for 2 hours and study activities will last up to 4 hours.

NCT04369599
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Device: V/Q Vest
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Improvement in oxygenation will be assessed by a demonstrated >20% increase in arterial oxygen levels after 180 minutes of treatment with the V/Q Vest, with two different levels of pressure. Normal levels of arterial oxygen range from 75 to 100 millimeters of mercury (mm Hg). Low oxygenation levels necessitate supplemental oxygen.

Measure: Change in Arterial Oxygenation Levels

Time: Baseline, Hour 1, Hour 2, Hour 3

Secondary Outcomes

Description: The study aims to determine if the vest is a predictor of response to more advanced therapy. The number of participants requiring advanced treatment will be documented.

Measure: Number of participants requiring advanced therapy

Time: Hour 3

Description: This study aims to determine if the vest allows avoidance in proning ventilation.

Measure: Number of participants avoiding proning ventilation

Time: Hour 3

Description: This study aims to determine if the vest allows for a delay in proning ventilation.

Measure: Number of participants delaying proning ventilation

Time: Hour 3
62 Construction of a Composite Clinical-echo Score Predictive of a Risk of Short-term Aggravation of Respiratory Impairment in Patients Suspected of Covid-19

With the influx of patients suspected of Covid-19 and the limited number of hospital beds, there is a need for sensitive triage to detect patients at risk of pulmonary complications and therefore requiring hospitalization, but also specific triage to safely discharge patients without risk factors or signs of clinical or ultrasound severity. The use of pulmonary ultrasound in addition to clinical assessment seems appropriate. Indeed, it allows early detection of signs of pneumopathy which, in the current context, most often correspond to Covid-19. These signs include B-lines, which indicate interstitial pulmonary oedema, and an anfractuous and thickened pleural line, or even centimetric parenchymal condensations with a low level of pleural effusion. Conversely, the presence of a medium to large pleural effusion is not very suggestive of the diagnosis of Covid-19. In addition, a lung ultrasound score has been developed and validated to assess the severity of acute respiratory distress and predict the occurrence of acute respiratory distress syndrome. It is based on the performance of a 12-point (6 per hemi-thorax) pulmonary ultrasound with the collection of the presence of B-lines, condensation or pleural effusion. In the hands of a trained operator, this examination takes only a few minutes. The aim of the study is to develop a score based on clinical and ultrasound evidence to allow early and safer referral than that based on clinical evidence alone. To do this, the study will retrospectively collect clinical and lung ultrasound data from departments that use this technique on a daily basis.

NCT04370249
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Other: pulmonary ultrasound
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Respiratory Insufficiency

Primary Outcomes

Description: Multivariate model predictive of clinical worsening of respiratory impairment within 48 hours post-admission : intubation, oxygenotherapy, need of vasoactive drugs, worsening of state,age, gender, body surface, LUScore (pulmonary ultrasound), FiO2, need of ventral decubitus, risk factor (obesity, asthma...), time from the beginning of the first symptoms

Measure: Construction of a composite clinical-echo score (VIRUScore) predictive of risk of worsening respiratory impairment in COVID-19 adult patients admitted to the Emergency Department

Time: 48 hours post-admission

Secondary Outcomes

Description: Sensitivity, specificity, positive predictive value, negative predictive value of VIRUScore on risk of pulmonary aggravation

Measure: Evaluate the prognostic performance of the VIRUScore on the risk of pulmonary aggravation

Time: 48 hours post-admission

Description: Sensitivity, specificity, positive predictive value, negative predictive value of VIRUScore on the risk of severe pulmonary aggravation defined by resuscitation admission and/or death.

Measure: Evaluate the prognostic performance of the VIRUScore on the risk of severe pulmonary aggravation defined by resuscitation admission and/or death at D14 (sensitivity, specificity, positive predictive value, negative predictive value).

Time: 14 days post-admission

Description: Research of VIRUScore cut-off values maximizing the negative predictive value and construction of a decisional algorithm maximizing returns home and transfers to non-specialized hospitals or clinics without loss of individual chance.

Measure: Construction of a decisional algorithm for triage and management of COVID-19 patients.

Time: 14 days post-admission

Description: Search for "Ultrasound signature" (lung fields and/or severity of damage) associated with mild vs. moderate (oxygen therapy) vs. severe (resuscitation/death) clinical forms.

Measure: Search for "ultrasound signature" (lung fields and/or severity of involvement) associated with mild (return home) vs. moderate (oxygen therapy) vs. severe (resuscitation/death) clinical forms.

Time: 14 days post-admission

Description: Diagnostic concordance of the LUScore and CT score with the severity grades defined by the French Radiology Society

Measure: Evaluate the analytical concordance between the pulmonary ultrasound (LUScore) and the Gold-standard CT-scan (CT score)

Time: 14 days post-admission

Description: Predictive Score for Aggravation in Patients Returned Home

Measure: Construction of a score predictive of aggravation in the sub-population of patients returned home

Time: 14 days post-admission
63 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
64 Mesenchymal Stromal Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

NCT04371393
Conditions
  1. Mesenchymal Stromal Cells
  2. Remestemcel-L
  3. Acute Respiratory Distress Syndrome
  4. COVID
Interventions
  1. Biological: Remestemcel-L
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of all-cause mortality within 30 days of randomization.

Measure: Number of all-cause mortality

Time: 30 days

Secondary Outcomes

Description: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.

Measure: Number of days alive off mechanical ventilatory support

Time: 60 days

Description: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.

Measure: Number of adverse events

Time: 30 days

Measure: Number of participants alive at day 7

Time: 7 days

Measure: Number of participants alive at day 14

Time: 14 days

Measure: Number of participants alive at day 60

Time: 60 days

Measure: Number of participants alive at day 90

Time: 90 days

Measure: Number of participants alive at 12 Months

Time: 12 Months

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 7

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 7 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 14

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 14 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 21

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 21 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 30

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 30 days

Description: severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Severity of ARDS

Time: baseline and 7 days

Description: severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Severity of ARDS

Time: baseline and 14 days

Description: severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Severity of ARDS

Time: baseline and 21 days

Description: severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

Measure: Severity of ARDS

Time: baseline and 30 days

Description: Hospital length of stay

Measure: Length of stay

Time: 12 months

Description: number of readmission

Measure: Readmissions

Time: 12 months

Measure: Length of Stay in Intensive Care Unit

Time: 12 months

Description: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 7 days

Description: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 14 days

Description: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 21 days

Description: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 30 days

Description: Changes from baseline in plasma hs-CRP concentration at days 7

Measure: Change in plasma hs-CRP concentration

Time: baseline and 7 days

Description: Changes from baseline in plasma hs-CRP concentration at days 14

Measure: Change in plasma hs-CRP concentration

Time: baseline and 14 days

Description: Changes from baseline in plasma hs-CRP concentration at days 21

Measure: Change in plasma hs-CRP concentration

Time: baseline and 21 days

Description: Changes from baseline in serum hs-CRP concentration at days 30

Measure: Change in serum hs-CRP concentration

Time: baseline and 30 days

Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 30 days

Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 30 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 7 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 14 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 21 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 30 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 30 days

Description: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization

Measure: Pulmonary symptoms

Time: 6 months

Description: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization

Measure: Pulmonary symptoms

Time: 12 months
65 WeanINg From Mechanical Ventilation for ARDS CovId-19 Patients Guided by Combined Thoracic UltraSound: a Prospective, Multicenter, Randomized, Open-label, Parallel-group Clinical Trial

The most feared complication of COVID-19 infection is the occurrence of an acute respiratory distress syndrome (ARDS) that requires ICU admission and prolonged mechanical ventilation in more than 2% of the affected patients. Establishing the correct time to extubate mechanically ventilated patients is a crucial issue in the critical care practice. Delayed extubation has several consequences such as patient's mortality, health-care-related complications, neuropsychological adverse events. The aim of the INVICTUS study is to evaluate whether a CTUS-based MV weaning strategy could reduce the duration of mechanical ventilation of ARDS COVID-19 ICU patients by 72 hours, compared with usual medical care.

NCT04372680
Conditions
  1. COVID-19
  2. ARDS, Human
  3. Mechanical Ventilation
Interventions
  1. Diagnostic Test: CTUS examination
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Delay from the start of MV weaning process (day of the switch from volume control mode to pressure support ventilation) to extubation (or spontaneously breathing through tracheostomy cannula) for at least 48h, as previously defined.

Measure: Delay from the start of Mechanical Ventilation weaning process to extubation

Time: day 28

Secondary Outcomes

Description: delay from intubation to extubation

Measure: delay from intubation to extubation

Time: day 28

Description: Successful of extubation if patient is not reintubated after 48 hours of extubation

Measure: Successful of extubation

Time: day 28

Description: mortality rate

Measure: mortality rate

Time: day 28
66 Human Ab Response & immunoMONItoring of COVID-19 Patients

Prospective, mono centric study on COVID-19 patients with or without acute respiratory distress syndrome (ARDS) to analyse the dynamics of the immune response and to search for biomarkers of evolution

NCT04373200
Conditions
  1. SARS-CoV-2 Coronavirus
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Blood samples collection
  2. Other: Saliva collection
MeSH:Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Blood sample

Measure: Number of increased immune population

Time: Month 4

Description: Blood sample

Measure: Number of decreased immune population

Time: Month 4

Description: Blood sample

Measure: Number of statically different phenotypes compared to control patients

Time: Month 4

Secondary Outcomes

Description: Qualitative identification of immune subpopulations showing a significant variation compared to controls and quantification of this variation (at D1 and/or D14)

Measure: Gain or loss of functional phenotypic markers between D1 and D14

Time: Day 14

Description: Qualitative identification of immune subpopulations showing a significant variation between acute and mild COVID-19 and quantification of this variation (at D1 and/or D14)

Measure: Gain or loss of functional phenotypic markers between between acute and mild infections

Time: Day 14

Description: Qualitative identification of immune subpopulations showing a significant variation between acute stage and recovery (at 4 months) and quantification of this variation

Measure: Gain or loss of functional phenotypic markers between D1 and month 4

Time: Month 4

Description: Blood sample

Measure: Evaluation of V, D, J gene usage alterations in the immunoglobulin and T cell receptor (TCR) repertoires during ARDS linked to COVID-19

Time: Day 14

Description: Blood sample

Measure: Identification of the Ig classes and of V, D, J sequences of anti-CoV-2 antibodies

Time: Month 4

Description: Blood sample

Measure: Characterization of a new set of human antibodies from patients who have recovered of COVID-19

Time: Month 4
67 Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19

The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety.

NCT04375735
Conditions
  1. ARDS, Human
  2. COVID-19
Interventions
  1. Drug: Bovine Lipid Extract Surfactant
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Count of any decreases in oxygenation, expressed as PaO2 (mmHg) / FiO2 (% oxygen as a decimal), of greater than 20% during the BLES treatment and up to 30 minutes post-treatment. Change will be calculated relative to pre-treatment values.

Measure: Adverse events (patient) - Decrease in oxygenation

Time: 3 days post-randomization

Description: Count of any decrease in mean arterial blood pressure >10 mmHg or requirement for >20% increase in vasopressor dose during the BLES procedure and up to 30 minutes post-treatment. Change will be calculated relative to the pre-treatment values.

Measure: Adverse events (patient) - Decrease in hemodynamics

Time: 3 days post-randomization

Description: Number of circuit breaches. Count of any circuit breach immediately prior to and during each BLES treatment procedure will be recorded.

Measure: Adverse event (healthcare worker) - Circuit breach

Time: 3 days post-randomization

Description: Count of healthcare personnel involved in the BLES procedure developing symptoms and testing positive for COVID-19.

Measure: Adverse event (healthcare worker) - COVID-19 symptoms

Time: 2 weeks post-randomization

Secondary Outcomes

Description: PaO2 (in mmHg) / FiO2 (percentage oxygen expressed as a decimal) ratios captured from clinical chart

Measure: Change in oxygenation

Time: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.

Description: Lung compliance captured from the ventilators, expressed in mL/cm H2O.

Measure: Change in Lung compliance

Time: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.

Description: The number of days the patient is receiving mechanical ventilation.

Measure: Ventilated days

Time: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days

Description: The number of days the patient is admitted to the ICU

Measure: Length of ICU stay

Time: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days

Description: The number of days the patient is admitted to the hospital

Measure: Length of hospital stay

Time: From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days

Description: Number of patients who die within 30 days of ICU admission

Measure: Mortality

Time: 30 days

Description: G-CSF, in pg/mL, from multiplex cytokine arrays

Measure: G-CSF levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: GM-CSF, in pg/mL, from multiplex cytokine arrays

Measure: GM-CSF levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: IFN gamma, in pg/mL, from multiplex cytokine arrays

Measure: IFN gamma levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: IL-1 beta, in pg/mL, from multiplex cytokine arrays

Measure: IL-1 beta levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: IL-4, in pg/mL, from multiplex cytokine arrays

Measure: IL-4 levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: IL-6, in pg/mL, from multiplex cytokine arrays

Measure: IL-6 levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: IL-10, in pg/mL, from multiplex cytokine arrays

Measure: IL-10 levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: I, in pg/mL, from multiplex cytokine arrays

Measure: I levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: MCP-1, in pg/mL, from multiplex cytokine arrays

Measure: MCP-1 levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)

Description: TNF alpha, in pg/mL, from multiplex cytokine arrays

Measure: TNF alpha levels (serum inflammatory biomarker)

Time: ICU day 0, 1, 3 and 7 (7 days)
68 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 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
69 CORONA: A Phase 1/2 Study Using DeltaRex-G Gene Therapy for Symptomatic COVID-19

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. COVID-19 causes life threatening complications known as Cytokine Release Syndrome or Cytokine Storm and Acute Respiratory Distress Syndrome. These complications are the main causes of death in this global pandemic. Over 1000 clinical trials are on-going worldwide to diagnose, treat, and improve the aggressive clinical course of COVID-19. The investigators propose the first, and so far, only gene therapy solution that has the potential to address this urgent unmet medical need. Rationale 1. There are striking similarities between the damaged lung environment of COVID-19 induced ARDS and the tumor microenvironment (exposed collagen from tissue destruction by invading tumor or by the virus-induced immune response, and presence of activated proliferative cells (cancer cells and tumor associated fibroblasts or activated T cells, macrophages and pulmonary fibroblasts in COVID-19); 2. DeltaRex-G is a disease-seeking retrovector encoding a cytocidal dominant negative human cyclin G1 as genetic payload). When injected intravenously, the DeltaRex-G nanoparticles has a navigational system that targets exposed collagenous proteins (XC proteins) in injured tissues (e.g. inflamed lung, kidney, etc.), thus increasing the effective drug concentration at the sites of injury, in the vicinity of activated/proliferative T cells evoked by COVID-19. Our hypothesis is that DeltaRex-G then enters the rapidly dividing T cells and kills them by arresting the G1cell division cycle, hence, reducing cytokine release and ARDS; 3. Intravenous DeltaRex-G has minimal systemic toxicity due to its navigational system (targeting properties) that limits the biodistribution of DeltaRex-G only to areas of injury where exposed collagenous (XC) proteins are abnormally found; and 4. DeltaRex-G is currently available in FDA approved "Right to Try" or Expanded Access Program for Stage 4 cancers for an intermediate size population. To gain this approval, FDA requires DeltaRex-G to have demonstrated safety and efficacy in early clinical trials.

NCT04378244
Conditions
  1. COVID-19
  2. Cytokine Storm
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: DeltaRex-G
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The study will employ the standard "cohort of three" design (Storer, 1989). Three patients are treated at each dose level with expansion to six patients per cohort if DLT is observed in one of the three initially-enrolled patients at each dose level. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. No intra-patient escalation will take place.

Measure: Maximum Tolerated Dose

Time: 3 weeks

Secondary Outcomes

Description: Duration of survival

Measure: Survival

Time: 2 months

Description: Time of hospital admission to time of discharge

Measure: Hospital Stay

Time: 3 weeks

Description: Time from start of mechanical ventilation to extubation or death

Measure: Ventilator Therapy

Time: 3 weeks

Description: Time from start of intensive care to discarge to regular room

Measure: Intensive Care Unit Stay

Time: 3 weeks

Description: Improvement in serum cytokine IL-6, IL12, TNF alpha

Measure: Cytokine Pattern

Time: 3 weeks
70 Characteristics and Outcomes of Patients With COVID-19 Admitted to the ICU

This is a case series of patients with COVID-19 admitted to the largest university hospital in Sao Paulo, Brazil, during the 2020 COVID-19 pandemic. Data will be collected prospectively and retrospectively. The main objective is to describe the characteristics of critically ill patients with COVID-19 and their clinical outcomes, and to identify risk factors associated with survival, to inform clinical decision-making and to guide the strategy to mitigate the epidemic, both within each hospital and ICU and in public health management.

NCT04378582
Conditions
  1. SARS-CoV 2
  2. Respiratory Distress Syndrome, Adult
  3. Corona Virus Infection
  4. Critical Illness
Interventions
  1. Other: risk factors
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Critical Illness

Primary Outcomes

Description: the proportion of patients who survive to ICU discharge or for 28 days in the ICU

Measure: ICU survival at 28 days

Time: 28 days

Secondary Outcomes

Description: the proportion of patients who survive to hospital discharge or for 60 days in the hospital

Measure: Hospital survival at 60 days

Time: 60 days

Description: Number of days under invasive ventilatory support

Measure: Duration of mechanical ventilation

Time: 28 days

Description: Proportion of patients who received renal replacement therapy during the ICU stay

Measure: Need for renal replacement therapy

Time: 28 days

Description: percentage of patients who developed complications during the ICU stay: thromboembolic events, ventilator associated pneumonia, secondary infections, cardiovascular complications

Measure: Complications during the ICU stay

Time: 28 days
71 A Study of Liposomal Trans Crocetin, LEAF-4L6715, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19, Sepsis or Other Causes

This is an open label phase II study of treatment with LEAF-4L6715 in patients who experience severe acute respiratory distress syndrome (ARDS) and are receiving artificial respiratory support due to COVID-19, Sepsis or other Causes. The purpose of this study is to evaluate the improvement in PaO2/FiO2 by more than 25% in patients treated with LEAF-4L6715.

NCT04378920
Conditions
  1. COVID19, Sepsis or Other Causes
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: LEAF-4L6715
MeSH:Sepsis Toxemia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
HPO:Sepsis

Primary Outcomes

Measure: proportion of patients showing an increase of at least 25% of PaO2/FiO2 ratio

Time: 24 hours

Secondary Outcomes

Measure: proportion of patients with a PaO2/FiO2 ratio above 200 mm Hg

Time: 24, 48 and 72 hours

Measure: all cause mortality

Time: 28 days
72 Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome in Referral Hospitals in Indonesia

Corona virus disease 2019 (COVID-19) has been declared as a Pandemic by the World Health Organization (WHO). According to WHO report on March 31st 2020, globally COVID-19 have infected over 750,000 people and caused over 36,000 deaths with case fatality rate of 4.85%. In Indonesia, COVID-19 have infected 1,414 people and caused 122 deaths with case fatality rate of 8.63%. In severe cases, COVID-19 causes complications, such as acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ dysfunction syndrome (MODS), where age and comorbid illnesses as a major factor to these complications. Up to this point there are several promising therapies for COVID-19 but is not yet recommended and in need of further research. The use of convalescent plasma has been approved by the US Food and Drug Administration (FDA) through the scheme of emergency investigational new drug (eIND). This method has been used as the treatment in several outbreak or plague cases over the years, such as the flu epidemic in 1918, polio, measles, mumps, SARS (severe acute respiratory syndrome), EVD (Ebola virus disease) and MERS (middle-eastern respiratory syndrome) and this treatment shows better outcome. Several case report on the use of convalescent plasma for COVID-19 patients with ARDS and mechanical ventilation has been reported and shows promising outcome. Nevertheless, larger and multicenter research need to be done to assess and evaluate the effectiveness and safety of convalescent plasma therapy on for COVID-19 patients with ARDS.

NCT04380935
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Convalescent plasma
  2. Drug: Standard of care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Proportion of all-cause mortality

Measure: All-cause mortality

Time: up to 28 days

Secondary Outcomes

Description: Mean length of stay in intensive care unit

Measure: Length of stay in intensive care unit

Time: up to 28 days

Description: Mean duration of mechanical ventilation

Measure: Duration of mechanical ventilation

Time: up to 28 days

Description: Mean change from baseline using time series analysis

Measure: Body temperature (degree in Celsius)

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: The Sequential Organ Failure Assessment (SOFA) Score

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: PAO2/FIO2 ratio

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: C-Reactive Protein (CRP) in mg/L

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: D-Dimer in ng/mL

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: Procalcitonin in ng/mL

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Mean change from baseline using time series analysis

Measure: Interleukin 6 (IL-6) in pg/mL

Time: Day 1, 3, 5, and 7 after administration of therapy

Description: Number of participants with allergic/ anaphylaxis transfusion reaction

Measure: Allergic/ anaphylaxis transfusion reaction

Time: 24 hours post-transfusion

Description: Number of participants with Hemolytic transfusion reaction

Measure: Hemolytic transfusion reaction

Time: 24 hours post-transfusion

Description: Number of participants with Transfusion Related Acute Lung Injury

Measure: Transfusion Related Acute Lung Injury

Time: 24 hours post-transfusion

Description: Number of participants with Transfusion associated Circulatory Overload

Measure: Transfusion associated Circulatory Overload

Time: 24 hours post-transfusion
73 Pulmonary and Motor Rehabilitation for People With COVID-19 in Intensive Care Units to Reduce Length of Stay in Hospital

COVID-19 DISEASE Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, severe acute respiratory syndrome from COVID-19, that was first recognized in Wuhan, China, in December 2019. While most people with COVID-19 develop mild or uncomplicated illness, approximately 14% develop severe disease requiring hospitalization and oxygen support and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by acute respiratory disease syndrome (ARDS) requiring prolonged mechanical ventilation, sepsis and septic shock, multiorgan failure, including acute kidney, liver and cardiac injury. ARDS REHABILITATION Critically ill people who undergo prolonged mechanical ventilation often develop weakness, with severe symmetrical weakness of and deconditioning of the proximal musculature and of the respiratory muscles (critical illness neuropathy/myopathy).These individuals also develop significant functional impairment and reduced health-related quality of life (HRQL) up to 2 and 5 years after discharge. ARDS survivors may complain of depression, anxiety, memory disturbances, and difficulty with concentration often unchanged at 2 and 5 years. Less than half of all ARDS survivors return to work within the first year following discharge, two-thirds at two years, and more than 70% at five years. Early physiotherapy (PT) of people with ARDS has recently been suggested as a complementary therapeutic tool to improve early and late outcomes. The aims of PT programs should be to reduce complications of immobilization and ventilator-dependency, to improve residual function, to prevent new hospitalisations, and to improve health status and HRQL. Physiotherapy in critical patients is claimed also to prevent and contribute to treat respiratory complications such as secretion retention, atelectasis, and pneumonia. Early mobilization and maintenance of muscle strength may reduce the risk of difficult weaning, limited mobility, and ventilator dependency. Lastly, pulmonary rehabilitation in ICU in mechanically ventilated subjects may reduce length of stay in ICU up to 4.5 day, shorten mechanical ventilation of 2.3 days and weaning by 1.7 days. The aim of this study is to investigate how early pulmonary and motor rehabilitation impacts on length of hospital admission (ICU and acute ward) and early and late outcomes inpatients that develop ARDS due to COVID-19.

NCT04381338
Conditions
  1. Corona Virus Disease 19 (COVID-19)
  2. COVID
  3. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  4. Critical Illness
Interventions
  1. Other: Pulmonary and Motor Rehabilitation
MeSH:Virus Diseases Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Critical Illness

Primary Outcomes

Description: days of ICU stay

Measure: Length of ICU stay

Time: up to 60 days

Secondary Outcomes

Description: days of hospital stay

Measure: Length of hospital stay

Time: up to 90 days
74 A Prospective, Randomized, Controlled Study Assessing Vagus Nerve Stimulation in CoViD-19 Respiratory Symptoms (SAVIORII)

The study is a prospective, randomized, controlled investigation designed for comparison of two groups for the reduction of respiratory distress in a CoViD-19 population, using gammaCore Sapphire (nVNS) plus standard of care (active) vs. standard of care alone (SoC), the control group. The gammaCore® (nVNS) treatments will be used acutely and prophylactically. The active and control groups will be diseased and severity matched. The primary objective is to reduce initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Secondary objectives are to evaluate cytokine trends/prevent cytokine storms, evaluate supplemental oxygen requirements, decrease mortality of CoViD-19 patients and to delay the onset of mechanical ventilation.

NCT04382391
Conditions
  1. COVID
  2. Corona Virus Infection
  3. Respiratory Failure
  4. Respiratory Distress Syndrome, Adult
  5. ARDS, Human
  6. SARS (Severe Acute Respiratory Syndrome)
Interventions
  1. Device: gammaCore® Sapphire (non-invasive vagus nerve stimulator)
  2. Other: Standard of care therapies
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome Signs and Symptoms, Respiratory

Primary Outcomes

Description: measure the change (in hours) between the control group and treatment group

Measure: change in initiation of mechanical ventilation in patients with CoViD-19 compared to the control group.

Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first, assessed up to 3 months

Secondary Outcomes

Description: measure the changes in the serum/plasma concentrations of TH1 and TH2-type cytokines

Measure: evaluate cytokine trends

Time: From the time of initial blood draw until the time of final blood draw, assessed up to date of mechanical ventilation, death, or discharge from hospital, whichever occurs first,assessed up to 3 months

Description: compare the difference in oxygen requirements (liters/min) between the control group and active group for patients admitted to the hospital for CoViD-19.

Measure: evaluate supplemental oxygen requirements

Time: From the time of randomization, assessed up to time of mechanical ventilation, day of discharge or death, whichever occurs first,assessed up to 3 months

Description: measure the change (in hours) to death between control group and treatment group

Measure: decrease mortality of CoViD-19 patients

Time: From the time or randomization until the date of death from any cause, assessed up to day of discharge or death,assessed up to 3 months

Description: measure the change (in hours) to time of mechanical ventilation between control group and treatment group

Measure: delay onset of ventilation

Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first,assessed up to 3 months
75 Outcome of COVID-19 Patients After Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Multicenter European Study

This study aims to investigate outcomes and predictors of outcome after extracorporeal membrane oxygenation (ECMO) therapy for severe acute respiratory syndrome (ARDS) in COVID-19 patients.

NCT04383678
Conditions
  1. COVID-19
  2. Extracorporeal Membrane Oxygenation Complication
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Device: Extracorporeal membrane oxygenation
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: In-hospital mortality

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Secondary Outcomes

Measure: Death on ECMO

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Stroke

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Blood stream infection

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Lung complications requiring surgical treatment

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Blood transfusion

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Acute kidney injury

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Duration of mechanical ventilation

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Deep vein thrombosis

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Pulmonary embolism

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Length of ICU stay

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Length of hospital stay

Time: During index hospital stay follow-up until 1 year after ECMO initiation

Measure: Death after hospital discharge

Time: During index hospital stay follow-up until 1 year after ECMO initiation
76 Inhaled Sedation in COVID-19-related Acute Respiratory Distress Syndrome (ISCA): an International Research Data Study in the Recent Context of Widespread Disease Resulting From the 2019 (SARS-CoV2) Coronavirus Pandemics (COVID-19)

The authors hypothesized that inhaled sedation, either with isoflurane or sevoflurane, might be associated with improved clinical outcomes in patients with COVID-19-related ARDS, compared to intravenous sedation. The authors therefore designed the "Inhaled Sedation for COVID-19-related ARDS" (ISCA) non-interventional, observational, multicenter study of data collected from the patients' medical records in order to: 1. assess the efficacy of inhaled sedation in improving a composite outcome of mortality and time off the ventilator at 28 days in patients with COVID-19-related ARDS, in comparison to a control group receiving intravenous sedation (primary objective), 2. investigate the effects of inhaled sedation, compared to intravenous sedation, on lung function as assessed by gas exchange and physiologic measures in patients with COVID-19-related ARDS (secondary objective), 3. report sedation practice patterns in critically ill patients during the COVID-19 pandemics (secondary objective).

NCT04383730
Conditions
  1. Critically Illness
  2. Sedation
  3. Invasive Mechanical Ventilation
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Intravenous sedation
  2. Drug: Inhaled sedation
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Ventilator-free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after intubation, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 27 or died prior to day 28, VFDs will be zero. Patients transferred to another hospital or other health care facility will be followed to day 28 to assess this endpoint.

Measure: Number of days off the ventilator (VFD28, for ventilator-free days), taking into account death as a competing event

Time: Day 28 after inclusion

Secondary Outcomes

Description: All-cause mortality

Measure: All-cause mortality

Time: Days 7, 14, and 28 after inclusion

Description: Ventilator-free days to days 7 and 14 are defined as the number of days from the time of initiating unassisted breathing to day 7 and 14 after intubation, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to days 7 and 14 If a patient returns to assisted breathing and subsequently achieves unassisted breathing to days 7 and 14 , VFDs will be counted from the end of the last period of assisted breathing to days 7 and 14. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 6 or 13 or died prior to days 7 and 14, respectively,VFDs to days 7 and 14 will be zero. Patients transferred to another hospital or other health care facility will be followed to days 7 and 14 to assess this endpoint.

Measure: Ventilator-free days

Time: Days 7 and 14 after inclusion

Description: Number of days alive and not in the ICU from inclusion to day 28

Measure: ICU-free days

Time: Day 28 after inclusion

Description: Total duration of controlled mechanical ventilation to day 28

Measure: Duration of invasive mechanical ventilation

Time: Day 28 after inclusion

Description: Total duration of controlled mechanical ventilation to day 28

Measure: Duration of controlled mechanical ventilation

Time: Day 28 after inclusion

Description: Arterial hypoxemia, as assessed by the partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio (PaO2/FiO2)

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Partial pressure of arterial carbon dioxide (PaCO2)

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Inspiratory plateau pressure

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Driving pressure

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Mode of mechanical ventilation (assisted versus controlled)

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: If available, 100 ms occlusion pressure (P0.1), a marker of respiratory drive

Measure: Physiological measures of lung function

Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusion

Description: Development of pneumothorax

Measure: Development of complications

Time: Day 7 from inclusion

Description: Supraventricular tachycardia

Measure: Development of complications

Time: Day 7 from inclusion

Description: New onset atrial fibrillation

Measure: Development of complications

Time: Day 7 from inclusion

Description: Total duration (in days) of vasopressor use

Measure: Duration of vasopressor use

Time: Day 28 after inclusion

Description: Total duration (in days)of renal replacement therapy

Measure: Duration of renal replacement therapy

Time: Day 28 after inclusion

Description: Adjuvant therapies are defined as: prone position, recruitment maneuvers, inhaled nitric oxide, inhaled epoprostenol sodium, high frequency ventilation, ECMO, neuromuscular blockade

Measure: Duration (in days) of any adjuvant therapies

Time: Day 7 from inclusion

Description: Number of days with continuous neuromuscular blockade

Measure: Duration of continuous neuromuscular blockade

Time: Day 28 from inclusion

Description: Sedation drug(s) used (name(s))

Measure: Type of sedation practices

Time: Day 28 from inclusion

Description: Number of days with sedation

Measure: Duration of sedation practices

Time: Day 28 from inclusion

Description: If inhaled sedation, device used to deliver it

Measure: Modalities of sedation practices

Time: Day 28 from inclusion
77 A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo

The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Zofin for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.

NCT04384445
Conditions
  1. Corona Virus Infection
  2. COVID-19
  3. SARS
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Zofin
  2. Other: Placebo
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician

Measure: Incidence of any infusion associated adverse events

Time: 60 Days

Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Measure: Incidence of Severe Adverse Events

Time: 60 Days

Secondary Outcomes

Description: Measured at day 60 or at hospital discharge, whichever comes first.

Measure: All Cause Mortality

Time: 60 Days

Description: Number of participants that are alive at 60 days post first infusion follow up

Measure: Survival Rate

Time: 60 Days

Description: Measure IL-6, TNF-alpha from serum of blood samples

Measure: Cytokine Levels

Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab

Measure: D-dimer Levels

Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Description: CRP from serum of blood samples

Measure: C-reactive protein Levels

Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Description: Viral load by real time RT methodology using blood samples or nose / throat swab

Measure: Quantification of the COVID-19

Time: Day 0, Day 4, Day 8

Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.

Measure: Improved Organ Failure

Time: Day 30

Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.

Measure: Chest Imaging Changes

Time: Day o, Day 30
78 Randomized Controlled Phase II Trial of Poractant Alfa (Curosurf®) by Fiberoptic Bronchoscopy-directed Endobronchial Administration in Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19 Viral Pneumonia

Surfactant replacement therapy (SRT) improves oxygenation and survival in NRDS and some infant ARDS. SRT was tried in adult ARDS with conflicting results. Research by Filoche and Grotberg helped to understand the failure of previous clinical trials and yielded a strong scientific rationale for SRT success, now allowing to design a new administration protocol for SRT in adults, to be tested by this clinical trial in COVID-19 adult ARDS patients. Patients will be randomized to receive either a bronchial fibroscopy alone (with aspiration of secretions) or a bronchial fibroscopy with administration of 3 mL/kg of a solution of poractant alpha diluted to 16 mg/mL and distributed into each of the 5 lobar bronchi.

NCT04384731
Conditions
  1. COVID-19
  2. ARDS, Human
Interventions
  1. Drug: poractant alfa
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Measure: Evolution of the PaO2 / FiO2 ratio between the measurements taken before (t0) and one hour after the end of the invasive procedure (H1).

Time: 1 hour post treatment

Secondary Outcomes

Measure: Oxygenation : PaO2 / FiO2 ratio.

Time: up to Day 1 and up to Day 7

Measure: Oxygenation : area under the PaO2 / FiO2 curve.

Time: up to Day 1 and up to Day 7

Measure: Oxygenation : area under the SpO2 curve.

Time: up to Hour 1 and up to Hour 24

Measure: Evolution of thoraco-pulmonary compliance (mL / mbar) between before and one hour after the procedure.

Time: 1 hour

Measure: Overall survival rate

Time: at 28 days, 56 days.

Measure: Mortality rate at discharge from the intensive care unit.

Time: through study completion, an average of 6 months.

Measure: Mortality rate at discharge from the hospital.

Time: through study completion, an average of 6 months.

Measure: Number of ventilator-free days

Time: Day 28, Day 56

Measure: Number of prone position sessions.

Time: up to 56 days

Measure: Time between inclusion and the last prone position session.

Time: up to 56 days
79 Characterization of the Clinical, Biological and Histological Pulmonary and Renal Damage Associated With the SARS-CoV-2 Syndrome in Patients Admitted in the Intensive Care Unit

Renal damage in patients hospitalized for ARDS in the ICU can also be related to multiple causes including, but not limited to, the consequences of hemodynamic fluctuations in these patients or the use of nephrotoxic drugs responsible for acute post-ischemic or toxic tubular necrosis. Frequently observed abnormalities of cioagumation may also have a potential impact on renal structures, particularly glomerular capillaries. The researchers wish to characterize and phenotype the renal impairment of patients hospitalized in intensive care with tables of severe Covid19 infections in ARDS: clinical, biological and histological (by performing post-mortem biopsies). Translated with www.DeepL.com/Translator (free version)

NCT04385004
Conditions
  1. Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Analysis of Clinical, Biological and Histological Pulmonary and Renal Impairment Related to SARS-CoV-2

Time: 1 month
80 Measurement of Airway Opening Pressure (AOP) in Patients With Acute Respiratory Distress Syndrom With Pressure Volume Curve on the Ventilator and With Electrical Impedance Tomography (EIT) Derived Method in Comparison of the Curves in Patients With or Without Covid 19 Pneumoniae.

Mechanical ventilation in ARDS requires protective ventilation and PEEP. Airway closer has to be overcome to reduce lung heterogeneity, AOP is measured globally with a ventilator PV curve without PEEP. EIT derived PV curve is another method that could determine heterogeneity of AOP between both lung. This study aims to determine whether AOP measured with EIT derived PV curve is similar to AOP on the ventilator PV curve and see if AOP is different between lungs. If airway closer is higher on one lung, global AOP on the ventilator PV curve probably estimates the other lung.

NCT04386720
Conditions
  1. Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: global ventilator method vs regional EIT derived method in all patients

Measure: Comparison of the PV curves

Time: At inclusion day

Secondary Outcomes

Description: Global ventilator method vs regional EIT derived method in regional AOP, right and left lungs

Measure: Comparison of regional AOP

Time: At inclusion day

Description: Comparison selected by the EIT-PEEP method

Measure: Comparison of the different AOPs with the level of PEEP

Time: At inclusion day
81 Predictors of Severe COVID-19 Outcomes (PRESCO)

This is a longitudinal, multi-center, observational study collecting diverse biological measurements and clinical and epidemiological data for the purpose of enabling a greater understanding of the onset of severe outcomes, primarily acute respiratory distress syndrome (ARDS) and/or mortality, in patients presenting to the hospital with suspicion or diagnosis of COVID-19. We seek to understand whether there are early signatures that predict progression to ARDS, mortality, and/or other comorbid conditions. The duration of the study participation is approximately 3 months.

NCT04388813
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Performance (discrimination / calibration) of models that predict the risk of development of ARDS and/or mortality among COVID-19 patients who present to the hospital for evaluation and treatment.

Measure: Performance (discrimination / calibration) of models

Time: From date of study enrollment until the date of first documented ARDS diagnosis or date of death from any cause, whichever comes first, assessed up to study end (estimated at 3 months).
82 Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS)

To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).

NCT04388826
Conditions
  1. Respiratory Distress Syndrome, Adult
Interventions
  1. Drug: Veru-111
MeSH:Severe Acute Resp Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision making is driven solely by resource limitation

Measure: Proportion of subjects that are alive without respiratory failure at Day 29.

Time: Day 29

Secondary Outcomes

Description: Improvement on the WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale)

Measure: WHO clinical Improvement

Time: Day15 Day 22 and Day 29

Description: Proportion of subjects with normalization of fever and oxygen saturation through

Measure: Normalization of Fever and Oxygen

Time: Day 15, Day 22, and Day 29

Description: Percentage of subjects discharged from hospital

Measure: Discharge from Hospital

Time: Day 15 and Day 22

Description: Proportion of patients alive and free of respiratory failure

Measure: Patients alive and free of respiratory failure

Time: Day 15, and Day 22
83 A Multicenter, Single-Treatment Study to Assess the Safety and Preliminary Efficacy of Lyophilized Lucinactant in Adults With COVID-19 Associated Acute Lung Injury

This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment.

NCT04389671
Conditions
  1. COVID-19
  2. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Interventions
  1. Drug: Lucinactant
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

Primary Outcomes

Description: The AUC for OI through 12 hours measured using the trapezoidal method, where OI is defined as mean airway pressure (Paw)×fraction of inspired oxygen (FiO2)×100/arterial pressure of oxygen (PaO2)

Measure: Oxygenation index (OI) area under the curve (AUC)0-12

Time: 12 hours post initiation of dosing

Secondary Outcomes

Description: FiO2 change from baseline

Measure: FiO2

Time: 24 hours post initiation of dosing

Description: PaO2 change from baseline

Measure: PaO2

Time: 24 hours post initiation of dosing

Description: SpO2 change from baseline

Measure: Oxygenation from pulse oximetry (SpO2)

Time: 24 hours post initiation of dosing

Description: Change from baseline in P/F ratio, defined as PaO2/FiO2

Measure: P/F ratio

Time: 24 hours post initiation of dosing

Description: Change from baseline in VI, defined as [respiration rate (RR)×(peak inspriatory pressure [PIP] - peak expiratory end pressure [PEEP])× arterial pressure of carbon dioxide (PaCO2)]/1000

Measure: Ventilation Index (VI)

Time: 24 hours post initiation of dosing

Description: Change from baseline in lung compliance, as measured by the ventilator

Measure: Lung compliance

Time: 24 hours post initiation of dosing
84 A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure

A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.

NCT04389840
Conditions
  1. COVID-19
  2. Acute Lung Injury
  3. SARS-CoV-2
Interventions
  1. Drug: Dociparastat sodium
  2. Drug: Placebo
MeSH:Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Alive and free of invasive mechanical ventilation

Measure: Proportion of participants who are alive and free of invasive mechanical ventilation

Time: Through Day 28

Secondary Outcomes

Description: Time to all-cause mortality

Measure: All-cause mortality

Time: Through Day 28
85 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

NCT04390139
Conditions
  1. COVID-19
  2. SARS-CoV 2
  3. Adult Respiratory Distress Syndrome
Interventions
  1. Drug: XCEL-UMC-BETA
  2. Other: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of patients who died, by treatment group

Measure: All-cause mortality at day 28

Time: Day 28

Secondary Outcomes

Description: Number of patients with treatment-emergent adverse events, by treatment group

Measure: Safety of WJ-MSC

Time: Day 28

Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group

Measure: Need for treatment with rescue medication

Time: Day 28

Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

Measure: Need and duration of mechanical ventilation

Time: Day 28

Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

Measure: Ventilator free days

Time: Day 28

Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

Measure: Evolution of PaO2 / FiO2 ratio

Time: Day 28

Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

Measure: Evolution of the SOFA index

Time: Day 28

Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

Measure: Evolution of the APACHE II score

Time: Day 28

Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

Measure: Duration of hospitalization

Time: Day 28

Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

Measure: Evolution of markers of immune response (leucocyte count, neutrophils)

Time: Day 28

Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: D-dimer

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: Ferritin

Time: Day 28

Other Outcomes

Description: Blood sample analysis

Measure: Analysis of subpopulations of lymphocytes and immunoglobulins

Time: Day 28

Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)

Measure: Evaluation of the in vitro response of the receptor lymphocytes

Time: Day 28

Description: Reactivity will be assessed using ELISPOT

Measure: Study of reactivity against SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis

Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis for the patient's genomic sequencing

Measure: Genetic variability of patient's genotype in response to treatment

Time: Day 28

Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment

Time: Day 28
86 Safety and Efficacy of Intravenous Infusion of Wharton's Jelly Derived Mesenchymal Stem Cell Plus Standard Therapy for the Treatment of Patients With Acute Respiratory Distress Syndrome Diagnosis Due to COVID 19: A Randomized Controlled Trial

Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis. Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation. These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.

NCT04390152
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Wharton's jelly derived Mesenchymal stem cells.
  2. Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.

Measure: Intergroup mortality difference with treatment

Time: 28 days.

Secondary Outcomes

Description: Safety evaluation of WJ-MSC describing and comparing incidence, type and severity of adverse events in both groups.

Measure: Number of patients with treatment related adverse events

Time: 6 months.

Description: Evaluation of the effect of WJ-MSC in the time of mechanical ventilation compared between the two groups, as prolonged mechanical ventilation days are associated with higher complication risks as pneumonia, tracheostomy and death.

Measure: Difference in days of mechanical ventilation between groups

Time: From ICU admission to 180 days.

Description: Evaluation of the effect of WJ-MSC in the time of hospitalization between the two groups as a measure of efficacy.

Measure: Median reduction of days of hospitalization

Time: From hospital admission to 180 days.

Description: Evaluation of the effect of WJ-MSC in the time of oxygen needs compared between the two groups as a measure of efficacy.

Measure: Median reduction of days of oxygen needs

Time: From hospital admission to 180 days.

Description: "Sequential Organ Failure Assessment" (SOFA) score is a tool used to determine the beginning and evolution of multiorgan failure, ranging from 0 to 24, being 24 the worst scenario. It has been proven useful as an outcome predictor of mortality and ICU stay. The result is the addition of the evaluation of each organ or system. Effect of WJ-MSC in the SOFA score will be compared between the two groups.

Measure: Difference between "Sequential Organ Failure Assessment" score between groups

Time: Baseline to 7 days

Description: Murray score is a tool used to classify lung injury. 0 = no lung injury, 0.1-2.5, mild to moderate lund injury, >2.5 Acute respiratory distress syndrome. The effect of WJ-MSC in the Murray score will be compared between the two groups.

Measure: Difference between median Murray score between groups

Time: Baseline and 7 days

Description: APACHE II is a prognostic score based on 12 different items obtained in the first 24 hours of ICU admission. Its mainly used as a single measure, but some authors have used and described prediction usefulness with repeated measures. It ranges from 0 to 71 points. Higher scores are related to higher ICU mortality. The effect of WJ-MSC in the APACHE II score will compared between the two groups.

Measure: Difference in APACHE II score between groups

Time: Baseline and 7 days

Description: Evaluation of the effect of WJ-MSC in lymphocyte count measured in absolute number/mm3. These laboratory measures have been associated with COVID 19 severity.

Measure: Difference in lymphocyte count between groups

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in C reactive protein concentration between the two groups, measured in mg/dl. Highest levels have been associated with COVID 19 severity and inflammation.

Measure: Changes in C reactive protein concentration between groups

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in D dimer between the two groups, measured in micrograms Highest levels have been associated with COVID 19 severity and thromboembolic complications.

Measure: Changes in D dimer concentration

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in ferritin compared between the two groups, measured in nanograms/ml. These laboratory measures have been associated with COVID 19 infection and severity.

Measure: Changes in ferritin concentration

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in LDH compared between the two groups, measured in units/liter. These laboratory measures have been associated with COVID 19 infection and severity.

Measure: Changes in lactate dehydrogenase concentration

Time: baseline and 21 days or discharge

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation.The effect of WJ-MSC in IL-6 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 6 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 8 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 8 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 10 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 10 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in TNF alpha will be compared between the two groups. It will be measured in nanograms/ml.

Measure: Impact on tumor necrosis factor alpha concentrations between groups.

Time: Baseline to 7 days.

Other Outcomes

Description: Evaluation of the effect of WJ-MSC in pulmonary function measured with 6 minute walk. 6 minute walk is a test that gives information about pulmonary, cardiovascular and musculoskeletal functions. It measures the distance walked in 6 minutes in meters.

Measure: Changes in 6 minute walk between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in pulmonary function with thoracic CT scan. CT scan gives information about lung parenchyma, showing acute and chronic changes related to the underlying condition. Radiologic findings will be compared mainly comparing percentage of patients with pulmonary fibrosis.

Measure: Changes in Pulmonary Computed Tomography Scan between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in pulmonary function measured with spirometry, compared between the two groups. Spirometry gives information about lung volume and mobilization of air. Main parameters to be measured in spirometry are Forced Vital Capacity, Forced Expiratory Volume in 1 second and relation between these two to define if there is obstruction or restriction of airflow.

Measure: Changes in Spirometry between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in health related quality of life assessed by 36 Item Short Survey (SF-36). SF 36 is a patient reported tool. Each question is rated from 0 to 100, being 100 the best score possible. The scores are then compared to a population defined median score. Differences in global and specific scoring will be measured between groups.

Measure: Changes in health related quality of life between groups

Time: 6 months
87 Effectiveness of Prone Positioning Combined With High-flow Nasal Cannula for Patients With COVID-19 Induced ARDS

Prone position (PP) has been proved to be effective in severe ARDS patients. On the other hand, High flow nasal cannula (HFNC) may prevent intubation in hypoxemic Acute respiratory failure (ARF) patients. Our hypothesis is that the combination of PP and HFNC in patients with COVID19 induced ARDS may decrease the need of mechanical ventilation. Primary outcome: Therapeutic failure within 28 days of randomization (death or intubation). Secondary outcomes: to analyze PP feasibility and safety in HFNC patients and to analyze effectiveness in terms of oxygenation. Methods: multicentric randomized study including patients with COVID19 induced ARDS supported with HFNC. Experimental group will received HFNC and PP whereas observation group will received standard care. Optimization of non-invasive respiratory management of COVID19 induced ARDS patients may decrease the need of invasive mechanical ventilation and subsequently ICU and hospital length of stay.

NCT04391140
Conditions
  1. COVID
  2. ARDS
  3. Acute Respiratory Distress Syndrome
  4. Acute Respiratory Failure
  5. Corona Virus Infection
Interventions
  1. Other: Prone position
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury

Primary Outcomes

Description: Therapeutic failure: death or intubation

Measure: Therapeutic failure death or intubation

Time: 28 days within randomization

Secondary Outcomes

Description: Comfort measurement using a visual-analog scale. Presence of complications related with prone position and the use of high-flow nasal cannula: Skin ulcers. Intravascular lines displacement HFNC related events (hot air feeling, nasal lesions)

Measure: Feasibility and safety of prone position in HFNC patients

Time: 28 days within randomization

Description: Evolution of the oxygenation (SpO2/FiO2) in prone position. Efficacy Length of HFNC therapy Length of ICU stay Length of mechanical ventilation (in those who require intubation) ICU and hospital mortality

Measure: Efficacy of prone position in HFNC patients

Time: 28 days within randomization
88 Inflammatory, Pulmonary, Physical & Neuropsychological Sequelae of COVID-19 Acute Respiratory Failure: A 1-Year Longitudinal Study

The novel SARS-CoV-2 virus has quickly spread worldwide, with substantial morbidity and mortality. There is very limited understanding of the short- and longer-term inflammatory/immunological and clinical course. However, the investigators expect survivors from severe COVID-19 to experience persistent functional impairments, as demonstrated in prior studies of patients with acute respiratory distress syndrome (ARDS) and other acute viral illnesses. Notably, however, few studies have ever investigated the biologic mechanisms underlying these functional impairments. Understanding these features of COVID-19 will improve the ability to design acute therapies and recovery-focused interventions. To address these knowledge gaps, the investigators propose a two-center, 225 patient longitudinal prospective cohort study of hospitalized COVID-19 patients with acute respiratory failure. Researchers will perform an in-depth evaluation of inflammatory/immunological biomarkers, and physical, pulmonary, and neuropsychological clinical outcomes during hospitalization, and over 3-, 6-, and 12-month follow-up.

NCT04393155
Conditions
  1. COVID-19
  2. Acute Respiratory Failure
Interventions
  1. Other: COVID-19+ observational
MeSH:Respiratory Insufficiency Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Exercise capacity

Measure: Six minute walk distance (6MWD)

Time: 3 months after hospital admission

Secondary Outcomes

Description: Exercise capacity

Measure: Six minute walk distance (6MWD)

Time: 6 months, 12 months after hospital admission

Description: Symptoms of anxiety and depression. Both anxiety and depression subscales are scored from 0-21, with higher scores indicating more symptoms.

Measure: Hospital Anxiety and Depression Scale (HADS)

Time: 3 months, 6 months, 12 months after hospital admission

Description: Health-related quality of life. The EQ-5D-5L is scored from 0-100, with a higher score indicating better health status.

Measure: EuroQol Group standardized measure of health status (EQ-5D-5L)

Time: 3 months, 6 months, 12 months after hospital admission

Description: Mental and Cognitive Functioning. The MoCA-BLIND is scored from 1-22, with higher scores indicating better cognitive function.

Measure: MoCA-BLIND

Time: 3 months, 6 months, 12 months after hospital admission

Description: Health Care Utilization

Measure: Health Care Utilization Survey (HUS)

Time: 3 months, 6 months, 12 months after hospital admission

Description: Mortality

Measure: Death

Time: 3 months, 6 months, 12 months after hospital admission

Description: The maximum volume of gas expired when the patient exhales as forcefully and rapidly as possible after a maximal inspiration. Obtained by spirometry.

Measure: Forced vital capacity (FVC)

Time: 3 months, 6 months, 12 months after hospital admission

Description: Measure of the volume expired over the first second of an FVC maneuver. Obtained by spirometry

Measure: Forced expiratory volume in 1 second (FEV1)

Time: 3 months, 6 months, 12 months after hospital admission

Description: Gait speed

Measure: 4-meter timed walk

Time: 3 months, 6 months, 12 months after hospital admission

Description: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.

Measure: Peripheral blood mononuclear cell type: CD4+ T cells (#cells/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.

Measure: Peripheral blood mononuclear cell type: CD8+ T cells (#cells/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.

Measure: Peripheral blood mononuclear cell type: B cells (#cells/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.

Measure: Peripheral blood mononuclear cell type: NK cells (#cells/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.

Measure: Peripheral blood mononuclear cell type: monocytes (#cells/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: C-Reactive Protein (CRP) (mg/l)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: Interleukin 6 (IL-6) (pg/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: Interleukin 8 (IL-8) (pg/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: Interferon gamma (IFNg) (pg/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: Interferon alpha (IFNa) (pg/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: Tumor necrosis factor alpha (TNFa) (pg/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Description: Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.

Measure: Circulating markers of inflammation: Interleukin 1 beta (IL-1b) (pg/ml)

Time: study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
89 The Critical Care Resources Adaptation to the SARS-CoV-2 Pandemic in Madrid

Description of the adaptation of ICUs in the region of Madrid to que surge in demand of critical care due to COVID-19

NCT04393324
Conditions
  1. COVID-19
  2. ARDS, Human
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: ICU mortality

Measure: Mortality

Time: 9 weeks

Secondary Outcomes

Description: From admission to discharge or death

Measure: Length of ICU stay

Time: 9 weeks
90 High Versus Low Dose Dexamethasone for the Treatment of COVID-19 Related ARDS: a Multicenter and Randomized Open-label Clinical Trial

There is compelling data indicating that there is an excessive inflammatory response in some patients with COVID-19 leading them to develop ARDS that can be severe with a very poor prognosis. Many of these patients require very long mechanical ventilation times to survive, which have led to the collapse of the health system in some regions of the world. The current evidence for the treatment of these severe forms is inconsistent and most scientific societies and governmental or international organizations recommend evaluating treatments with randomized clinical trials. Corticosteroids, being non-specific anti-inflammatory drugs, could shorten the duration of respiratory failure and improve the prognosis. Due to the lack of solid data available regarding this serious disease, our objective is to randomly evaluate the efficacy and safety of the use of dexamethasone, a parenteral corticosteroid approved in Argentina, in patients with ARDS with confirmed respiratory infection due to SARS-CoV-2 (COVID-19). After RECOVERY trial prepublication, low dose (6 mg QD for 10 days) dexamethasone was recommended as the usual care treatment for severe COVID-19. At this time only 3 patients had been included in the trial. Thus, we updated our recommendations for centers and decided to compare two different doses of this glucocorticoid for the treatment of ADRS due to COVID-19.

NCT04395105
Conditions
  1. Respiratory Distress Syndrome, Adult
  2. Covid-19
Interventions
  1. Drug: Dexamethasone (high dose)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Days without ventilator support in the first 28 days following randomization

Measure: Ventilator-free days at 28 days

Time: 28 days after randomization

Secondary Outcomes

Description: Dead rate within 28 days of randomization

Measure: 28-days mortality

Time: 28 days after randomization

Description: Frequency of ventilator associated pneumonia, blood stream infection or candidemia in the first 28 days following randomization

Measure: Frequency of nosocomila infections

Time: 28 days after randomization

Description: Frequency of positive PCR on nasopharingeal swab

Measure: Viral shedding

Time: 28 days after randomization

Description: Change from baseline CPR

Measure: Serum C-reactive Protein variation

Time: 10 days after randomization

Description: Variation in SOFA over the first 10 days after randomization

Measure: SOFA variation

Time: 10 days after randomization

Description: Cumulative hours spent on prone position

Measure: Use of prone position

Time: 10 days after randomization

Description: Frequency of delirium at ICU discharge

Measure: Delirium

Time: 28 days after randomization

Description: mMRC score at ICU discharge

Measure: Muscle weakness

Time: 28 days after randomization

Description: Death rate within 90 days of randomization

Measure: 90-day mortality

Time: 90 days after randomization
91 Randomized-controlled Trial of HFNC Alone vs HFNC and Awake Self-proning for Treatment of Severe COVID-19

Prone positioning is an established intervention in mechanically ventilated acute respiratory distress syndrome (ARDS) patients, with demonstrated reductions in mortality. Preliminary data suggest that awake proning in patients with COVID-19 treated with high-flow nasal oxygenation (HFNO) improves gas exchanges, and might be associated with a reduced need of mechanical ventilation, and reduced mortality. Further investigation in a formal randomized-controlled trial is need.

NCT04395144
Conditions
  1. Coronavirus Infection
  2. COVID
  3. Severe Acute Respiratory Syndrome
  4. Respiratory Failure
  5. Respiratory Insufficiency
  6. Respiratory Distress Syndrome
  7. ARDS
  8. Lung Diseases
Interventions
  1. Procedure: Awake Prone Positioning
  2. Procedure: Standard care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Pulmonary Valve Insufficiency Syndrome
HPO:Abnormal lung morphology Pulmonary insufficiency

Primary Outcomes

Measure: Rate of Therapeutic failure, defined as a combined outcome of rate of intubation or death

Time: Up to 28 days after randomization

Secondary Outcomes

Measure: Intubation rate

Time: Up to 28 days after randomization

Measure: Mortality

Time: Up to 28 days after randomization

Measure: Days spent on mechanical ventilation

Time: Until discharge, up to 24 weeks after randomization

Measure: Days spent in the ICU

Time: Until discharge, up to 24 weeks after randomization

Measure: Hospital stay (in days)

Time: From admission to discharge, up to 24 weeks after randomization

Other Outcomes

Description: Total time spent in prone position, as recorded by nursing or respiratory therapists

Measure: Time in prone position

Time: Up to 28 days post randomization

Description: Daily evolution of oxygenation

Measure: Oxygenation (SpO2/FiO2 ratio)

Time: Until HFNC weaning, or up to 14 days after randomization, whichever is first
92 A Phase 2 Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor, AMY-101, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 (SAVE)

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection. We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.

NCT04395456
Conditions
  1. Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)
Interventions
  1. Drug: AMY-101
  2. Other: WFI 5% glucose
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: The proportion of patients who are alive, without evidence of ARDS (i.e. PaO2/FIO2 >300 mm Hg), who do not require any oxygen support (in room air).

Time: 21 days

Description: The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.

Measure: The proportion of patients assigned to each category, of a six-category ordinal scale.

Time: 21 days

Secondary Outcomes

Description: The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.

Measure: The proportion of patients assigned to each category, of a six-category ordinal scale.

Time: On days 7, 14, and 44

Measure: Proportion of patients surviving

Time: Through to day 44

Description: With respiratory failure defined as any of the following: Worsening of severe gas transfer deficit, accounting for a shift in ARDS disease category (PaO2/FiO2 ≤200 for patients with PaO2/FiO2 >200 at baseline; PaO2/FiO2 ≤100 for patients with PaO2/FiO2 >100 at baseline), Persistent respiratory distress while receiving oxygen (persistent marked dyspnea,use of accessory respiratory muscles, paradoxical respiratory movements), Transfer to the intensive care unit for intubation, Death.

Measure: Proportion of respiratory failure-free survival

Time: Day 44

Measure: Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)

Time: Through day 44

Measure: Cumulative incidence of freedom from oxygen requirement

Time: Through day 44

Measure: Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS

Time: Within 14 days after inclusion in the study

Measure: Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS

Time: Within 14 days after inclusion in the study

Measure: Proportion of patients developing thrombotic microangiopathies

Time: Through day 44

Measure: Changes in PaO2 and PaO2/FIO2

Time: Through day 44

Measure: Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)

Time: Through day 44

Measure: Changes in maximal and minimal cardiovascular parameters: Respiratory rate

Time: Through day 44

Measure: Changes in maximal and minimal cardiovascular parameters: Heart Rate

Time: Through day 44

Measure: Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Length of stay in ICU

Time: Through day 44

Measure: Cumulative incidence of discharge from hospital

Time: Through day 44

Measure: Number of adverse events

Time: Through day 44

Measure: Changes in levels of anti-drug antibodies

Time: On day 0 , 14 and 44

Measure: Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of Club Cell protein CC16 (biomarker of lung damage )

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of AMY-101 plasma level

Time: On days 1, 2, 4, 7, 10, 14, 15, 21
93 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
94 Nebulized Heparin vs. Placebo for the Treatment of COVID-19 Induced Lung Injury

Randomized, placebo controlled study to determine if nebulized heparin may reduce the severity of lung injury caused by the novel coronavirus, also known as COVID-19

NCT04397510
Conditions
  1. Covid-19
  2. ARDS, Human
  3. Acute Lung Injury
Interventions
  1. Drug: Heparin
  2. Drug: 0.9% Sodium-chloride
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Measure: Mean daily PaO2 to FiO2 ratio

Time: 10 days

Secondary Outcomes

Measure: Duration of mechanical ventilation

Time: 30 days

Measure: ICU length of stay

Time: 30 days

Measure: Mortality Rate

Time: 30 days

Measure: Incidence of adverse drug events

Time: 10 days
95 Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19) the Vanguard Study

The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). ARDS often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world's first clinical trial using MSC therapy for patients with severe infections (sepsis) which is often associated with ARDS (NCT02421484). This trial demonstrated tolerability, and potential signs of efficacy. In addition, the investigators have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in three different clinical studies. The investigators propose a Phase 1, open label, dose-escalating and safety trial using a 3+3+3 design to determine the safety, and maximum feasible tolerated dose of repeated delivery of Bone Marrow (BM)-MSCs intravenously. This will take advantage of a limited supply of screened BM-MSCs lines which are available now in the GMP facility and will allow to have product ready to deliver to the first patient within weeks. The investigators will enroll up to 9 patients; each receiving repeated unit doses of BM-MSCs delivered by IV infusion on each of 3 consecutive days (24±4 hours apart) according to the following dose-escalation schedule (3 patients per dose panel): (i) Panel 1: 25 million cells/unit dose (cumulative dose: 75 million MSCs), (ii) Panel 2: 50 million cells/unit dose (cumulative dose: 150 million MSCs), (iii) Panel 3: up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs).

NCT04400032
Conditions
  1. Acute Respir
  2. Acute Respiratory Distress Syndrome
  3. Covid19
Interventions
  1. Biological: Mesenchymal Stromal Cells
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 to determine the maximum feasible tolerated dose (MFTD) of BM-MSCs given to patients with COVID-19

Measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

Time: At time of infusion until one year post-infusion

Secondary Outcomes

Description: Number of Participants alive by Day 28

Measure: Number of Participants alive by Day 28

Time: Day 28

Description: Number of Participants with ventilator-free Days by Day 28

Measure: Number of Participants with ventilator-free Days by Day 28

Time: Day 28
96 Using GM-CSF as a Host Directed Therapeutic Against COVID-19 - a Phase 2 Investigator Initiated Trial

The coronavirus disease 2019 (COVID-19) has rapidly become a pandemic. COVID-19 poses a mortality risk of 3-7%, rising to 20% in older patients with co-morbidities. Of all infected patients, 15-20% will develop severe respiratory symptoms necessitating hospital admission. Around 5% of patients will require invasive mechanical ventilation, and up to 50% will die. Evidence in severe COVID-19 suggests that these patients experience cytokine storm and progressed rapidly with acute respiratory distress syndrome and eventual multi-organ failure. Early identification and immediate treatment of hyperinflammation is thus recommended to reduce mortality. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) has been shown to be a myelopoietic growth factor that has pleiotropic effects in promoting the differentiation of immature precursors into polymorphonuclear neutrophils, monocytes/ macrophages and dendritic cells, and also in controlling the function of fully mature myeloid cells. It plays an important role in priming monocytes for production of proinflammatory cytokines under TLR and NLR stimulation. It has a broad impact on the processes driving DC differentiation and affects DC effector function at the mature state. Importantly, GM-CSF plays a critical role in host defense and stimulating antiviral immunity. Detailed studies have also shown that GM-CSF is necessary for the maturation of alveolar macrophages from foetal monocytes and the maintenance of these cells in adulthood. The known toxicology, pharmacologic and safety data also support the use of Leukine® in hypoxic respiratory failure and ARDS due to COVID-19. This study aims to recruit patients with evidence of pneumonia and hypoxia who have increased risk for severe disease and need for mechanical ventilation. The overall hypothesis is that GM-CSF has antiviral immunity, can provide the stimulus to restore immune homeostasis in the lung with acute lung injury from COVID-19, and can promote lung repair mechanisms, which would lead to improvement in lung oxygenation parameters.

NCT04400929
Conditions
  1. COVID
  2. Sars-CoV2
  3. ARDS, Human
Interventions
  1. Drug: Sargramostim
  2. Other: Normal Saline 0.9%
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: To measure the effectiveness of Leukine® in restoring lung homeostasis, the primary endpoint of this intervention is measuring oxygenation after 5 days of intravenous treatment through assessment of pre-treatment and post-treatment ratio of PaO2/FiO2, and through measurement of the P(A-a)O2 gradient, which can easily be performed in the setting of clinical observation of inpatients.

Measure: Measuring oxygenation

Time: Day 1 to Day 6
97 Treatment of Lung Injury From COVID-19 Infection With Intravenous Sodium Nitrite: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Study

This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Nitrite Injection for treatment of patients infected with COVID-19 who develop lung injury and require mechanical ventilation.

NCT04401527
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Acute Respiratory Failure
Interventions
  1. Drug: Sodium Nitrite
  2. Drug: Normal Saline
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury

Primary Outcomes

Description: Proportion of study subjects who are alive and free of respiratory failure at Day 28

Measure: Survival with Unassisted Breathing

Time: Day 28

Secondary Outcomes

Description: Number of days alive without mechanical ventilation from start of study through Day 28

Measure: Survival without Mechanical Ventilation

Time: Day 28

Description: Number of days alive and not in the intensive care unit from start of study through Day 28.

Measure: Survival without Intensive Care

Time: Day 28

Description: Number of days alive and not in hospital from start of study through Day 28.

Measure: Survival without Hospitalization

Time: Day 28

Description: Alive on Day 28 and no use of ECMO therapy any time between start of study and Day 28.

Measure: Survival without ECMO

Time: Day 28

Description: Alive on Day 28

Measure: Survival

Time: Day 28

Other Outcomes

Description: Oxygenation index (PaO2/FIO2) at Day 14

Measure: Lung Status

Time: Day 14

Description: Blood urea nitrogen (BUN) at Day 14

Measure: Kidney Status (1)

Time: Day 14

Description: Creatinine at Day 14

Measure: Kidney Status (2)

Time: Day 14

Description: Liver function tests (ALT and AST) at Day 14

Measure: Liver Status

Time: Day 14
98 A Randomized, Double-Blinded, Vehicle-Controlled, Multicenter, Parallel-Group Study of APL-9 in Mild to Moderate Acute Respiratory Distress Syndrome Due to COVID-19

The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are hospitalized and require supplemental oxygen therapy with or without mechanical ventilation. It is thought that COVID-19 activates the complement system, part of the immune system that responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has been designed to inhibit or block activation of part of the complement pathway, and potentially reduce inflammation in the lungs. Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9 plus standard of care. Part 2 of the study is double-blind, randomized; participants will receive either APL-9 or the vehicle-control plus standard of care.

NCT04402060
Conditions
  1. COVID
  2. Covid-19
  3. Coronavirus
  4. Coronavirus Infection
  5. Severe Acute Respiratory Syndrome
  6. Severe Acute Respiratory Syndrome Coronavirus 2
  7. Sars-CoV2
  8. Ards
  9. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: APL-9
  2. Other: Vehicle Control
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Cumulative incidence of treatment-emergent serious adverse events and treatment-emergent adverse events.

Time: Day 1 through Day 51

Secondary Outcomes

Measure: Hospital length of stay

Time: Day 1 through Day 21

Measure: Any cause of mortality

Time: Day 1 through day 58

Description: The minimum value is 0 and maximum value is 24. The higher a score the worse the outcome.

Measure: Sequential Organ Failure Assessment

Time: Day 1 through day 21

Measure: Total duration of mechanical ventilation and/or oxygen therapy

Time: Day 1 through day 21

Measure: Total duration of oxygen therapy

Time: Day 1 through day 21
99 Stellate Ganglion Block (SGB) for COVID-19 Acute Respiratory Distress Syndrome (ARDS)

The purpose of this study is to understand if it is safe and useful to perform SGB (Stellate Ganglion Block) in patients who have severe lung injury Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 infection.

NCT04402840
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Procedure: Stellate Ganglion Block
MeSH:Ganglion Cysts Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Adverse events that can atleast unlikely be attributed to SGB

Measure: Adverse events related to SGB

Time: 3 Months

Description: All adverse events related to COVID-19

Measure: All Adverse events

Time: 3 Months

Description: Death due to any cause

Measure: Death

Time: 3 Months

Secondary Outcomes

Description: Change from baseline clinical respiratory/pulmonary function as assessed by change in PF ratio

Measure: Assessment of respiratory/ pulmonary function

Time: 3 Months

Description: Change from last imaging data obtained prior to SGB procedure

Measure: Radiographic criteria

Time: 3 Months

Description: Change from baseline clinical cardiac function as assessed by improvement in arrhythmia as measured by standard of care ECG ( rate, rhythm and / or any aberrant electro physiological changes)

Measure: Cardiac function

Time: 3 Months
100 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
101 A Prospective Randomized Trial of Prone Positioning Versus Usual Care for Patients With Do-not-intubate Goals of Care and Hypoxemic Respiratory Failure During the Coronavirus SARS-CoV-2 (COVID-19) Pandemic

The purpose of this trial is to determine whether Prone Positioning (PP) improves outcomes for non-intubated hospitalized patients with hypoxemic respiratory failure due to COVID-19, who are not candidates for mechanical ventilation in the ICU. The investigators hypothesize that PP will reduce in-hospital mortality or discharge to hospice, compared with usual care for non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory failure due to probable COVID-19.

NCT04402879
Conditions
  1. Severe Acute Respiratory Syndrome Coronavirus 2
  2. COVID-19
  3. Acute Respiratory Distress Syndrome
  4. ARDS
  5. Hypoxemic Respiratory Failure
Interventions
  1. Procedure: Prone Positioning (PP)
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

Primary Outcomes

Description: In-hospital mortality or discharge to hospice at Day 60.

Measure: Hospital mortality or discharge to hospice

Time: 60 days

Secondary Outcomes

Description: An Adverse Event (AE) is any unfavourable or other finding (including clinically significant laboratory tests), symptom or disease occurring during the during of the study, whether or not it is considered to be related to the medicinal (investigational) product, not explicitly classified elsewhere in this protocol, and whether or not it is expected. A Serious Adverse Event (AE) is any unfavourable medical finding (including clinically significant laboratory tests) at any dose that: Results in death (primary outcome) Is life threatening Results in persistent of significant disability or incapacity Requires in in-patient hospitalisation or prolongation of Hospitalisation

Measure: Adverse Events and Serious Adverse Events

Time: 60 days

Description: Change in SpO2 during each PP session (SpO2 in prone position - SpO2 prior to prone positioning). Clinicians will be asked to record this change for the first proning session per shift (for 12 hour shifts this will result in 2 proning sessions being documented per 24 hour period, and for 8 hour shifts this will result in 3 proning sessions being documented per 24 hour period).

Measure: Change in SpO2

Time: 60 days

Description: Number of hospital free days in the 60 days after enrolment.

Measure: Hospital free days

Time: 60 days

Description: Admission to the Intensive Care Unit.

Measure: Admission to ICU

Time: 60 days

Description: Patient is intubated and requires mechanical ventilation.

Measure: Intubation and mechanical ventilation

Time: 60 days

Description: Patient requires non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).

Measure: Initiation of non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).

Time: 60 days

Description: The number of oxygen-free days at Day 60 (censored at discharge).

Measure: Oxygen-free days

Time: 60 days

Description: Time from admission to all-cause in-hospital death.

Measure: In-hospital death (time)

Time: 60 days

Description: Death at 90 days.

Measure: Death at 90 days

Time: 90 days
102 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
103 Efficacy and Safety of Angiotensin II Use in COVID-19 Patients With Acute Respiratory Distress Syndrome

This study aims to find out whether the use of angiotensin II, which is a drug to raise blood pressure has been approved by European Medical Agency in August 2019, as an add-on medication to increase blood pressure in patients with COVID-19, acute severe lung injury, inflammation and severe shock, compared with standard medication. In addition, the investigators will collect the data of Anakinra, another drug which is frequently used in this condition to reduce inflammation. The investigators will collect clinical data and outcomes from critical care patients. The investigators will analyse for whom these drugs are most beneficial and explore whether there are any patients who don't benefit or have side effects.

NCT04408326
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Angiotensin II
  2. Drug: Interleukin-1 receptor antagonist
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Percentage

Measure: Proportions of patients with mean arterial pressure ≥ 65 mmHg or an increase of mean arterial pressure ≥10 mmHg at 3 hours

Time: 3 hours

Secondary Outcomes

Description: microgram/kg/min

Measure: Noradrenaline dose

Time: 1 hour and 3 hours

Description: Changes in score, minimum 0, maximum 24, the higher score showing worse prognosis

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: baseline, 24, and 48 hours

Description: Patients who are alive and do not require renal replacement therapy at 28 days

Measure: RRT-free days

Time: 28 days

Description: Proportions of patients who do not require renal replacement therapy

Measure: RRT discontinuation

Time: 7 and 28 days

Description: micromol/L

Measure: Serum creatinine

Time: 7 days and 28 days

Description: Changes in value

Measure: PaO2/FiO2 ratio

Time: baseline, 24, and 48 hours

Description: Mortality rate

Measure: Mortality

Time: 7 days and 28 days

Description: e.g. arrhythmia, thromboembolism, etc.

Measure: Adverse events

Time: 28 days

Description: Change in serum C-reactive protein

Measure: Change in serum C-reactive protein

Time: 7 days

Description: Change in serum ferritin

Measure: Change in serum ferritin

Time: 7 days
104 Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome

This multicentric prospective clinical practice study aims at evaluating clinical factors associated with a prolonged invasive mechanical ventilation and other outcomes such as mortality and ICU length of stay in patients affected from COVID-19 related pneumonia and ARDS.

NCT04411459
Conditions
  1. COVID-19
  2. Mechanical Ventilation
  3. Quality of Life
  4. Radiologic Increased Density of Lung
  5. Sedation
  6. Complication of Treatment
Interventions
  1. Other: Invasive mechanical ventilation
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Ventilator free days (VFDs) will be calculated in a time frame of 28 days, the beginning of observation will coincide with the day of intubation and observation will end after successful disconnection from mechanical ventilation. For intubated patients, post extubation non invasive ventilation (NIV) will not be accounted as a ventilation period, in case of interval reintubation within 28 days, VFDs will be counted from the last successful extubation. For tracheostomized patients, ventilator free days will be counted after successful disconnection from mechanical ventilation and interval reconnections will be considered in the ventilation interval as for intubated patients.

Measure: Duration of mechanical ventilation and 28 days ventilator free days

Time: 28 days

Secondary Outcomes

Measure: ICU Mortality

Time: 60 days

Measure: 30 days survival after ICU discharge

Time: 30 days

Measure: 90 days survival after ICU discharge

Time: 90 days

Description: 15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY

Measure: Quality of life at 90 days after ICU discharge measured with 15D instrument

Time: 90 days

Description: First available CT, last CT before ICU admission and intubation, last ICU follow-up CT. First available chest X ray, last chest X ray before ICU admission and intubation, last ICU- follow up chest X ray and 30 days follow-up CT (if available) will be evaluated, if available. Structured description CT scan Date: yyyy/mm/dd Parenchymal alterations: ground glass, crazy paving, parenchymal consolidation Extension: monolateral, bilateral Number of lobes involved: (1-5) Percentage of parenchymal involvement: 0-100% Distribution: subpleural, random, diffuse X-ray scan Date: yyyy/mm/dd Main aspects: normal, focal lesions, monolateral multifocal lesions (right/left), diffuse multifocal lesions Lesion aspects: interstitial, interstitial/alveolar, alveolar, consolidations Pleural effusion presence and entity Pulmonary involvement score: 0 = no involvement =< 25% = 25-50% 3= 50-75% 4 => 75% Total score (0-6): score of the right lung + score of the left lung

Measure: Radiologic aspects - structured description of CT and RX data

Time: 90 days
105 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
106 Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease

The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19 patients. The study was approved by the ethical committee of the Egyptian Center for Research and Regenerative Medicine in 11-5-2020.

NCT04412395
Conditions
  1. Corona Virus Infection
  2. Middle East Respiratory Syndrome (MERS)
  3. Acute Respiratory Distress Syndrome
  4. Coronavirus Infection
  5. COVID-19
  6. SARS-CoV 2
Interventions
  1. Dietary Supplement: Lactoferrin (Apolactoferrin)
  2. Drug: Placebo of excipient(s) will be administered
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Comparing the influence of the intervention on the Survival rate.

Measure: Survival rate.

Time: up to 8 weeks.

Description: For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT - For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.

Measure: Rate of disease remission.

Time: up to 4 weeks.

Description: Comparing the influence of the intervention on the PCR negative results.

Measure: The number of patients with PCR negative results.

Time: up to 4 weeks.

Secondary Outcomes

Description: Recording the changes from severe to moderate or mild and the time taken.

Measure: Mean change in the disease severity (clinical assessment).

Time: up to 4 weeks.

Description: Recording the changes in blood pressure mmHg.

Measure: Mean change in blood pressure.

Time: up to 4 weeks.

Description: Recording the changes in heart rate in beat/second.

Measure: Mean change in heart beats.

Time: up to 4 weeks.

Description: Recording the changes in body temperature in Celsius.

Measure: Mean change in body temperature.

Time: up to 4 weeks.

Description: Recording the changes in the respiratory rate in breath/minute.

Measure: Mean change in body respiratory rate.

Time: up to 4 weeks.

Description: Recording the changes in arterial oxygen saturation in mmHg.

Measure: Mean change in oxygen saturation.

Time: up to 4 weeks.

Description: Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).

Measure: Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).

Time: up to 4 weeks.

Description: Recording the changes in complete blood picture (CBC) in cells per liter.

Measure: Mean change in complete blood picture (CBC).

Time: up to 4 weeks.

Description: Recording the changes in C reactive protein (CRP) in mg/L.

Measure: Mean change in C reactive protein (CRP).

Time: up to 4 weeks.

Description: Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.

Measure: Mean change in erythrocyte sedimentation rate (ESR).

Time: up to 4 weeks.

Description: Recording the changes in D-dimer in ng/mL.

Measure: Mean change in D-dimer.

Time: up to 4 weeks.

Description: Recording the changes in ferritin in ng/mL.

Measure: Mean change in ferritin.

Time: up to 4 weeks.

Description: Recording the changes in liver Albumin in g/L.

Measure: Mean change in liver Albumin.

Time: up to 4 weeks.

Description: Recording the changes in total and direct Bilirubin in mg/dL.

Measure: Mean change in total and direct Bilirubin.

Time: up to 4 weeks.

Description: Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).

Measure: Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).

Time: up to 4 weeks.

Description: Recording the changes in aspartate aminotransferase (AST) in IU/L.

Measure: Mean change in aspartate aminotransferase (AST).

Time: up to 4 weeks.

Description: Recording the changes in Alanine Aminotransferase (ALT) in IU/L.

Measure: Mean change in Alanine Aminotransferase (ALT).

Time: up to 4 weeks.

Description: Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.

Measure: Mean change in Blood Urea Nitrogen (BUN).

Time: up to 4 weeks.

Description: Recording the changes in Serum Creatinine in mg/dL.

Measure: Mean change in Serum Creatinine.

Time: up to 4 weeks.

Description: Recording the changes in Serum Creatinine in ml/min.

Measure: Mean change in Serum Creatinine clearance.

Time: up to 4 weeks.

Description: Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.

Measure: Mean change in Glomerular filtration rate (GFR ).

Time: up to 4 weeks.

Description: Recording the changes in interleukin-1 (IL-1) in pg/ml.

Measure: The mean change in serum interleukin-1 (IL-1).

Time: up to 4 weeks.

Description: Recording the changes in interleukin-6 (IL-6) in pg/ml.

Measure: The mean change in serum interleukin-6 (IL-6).

Time: up to 4 weeks.

Description: Recording the changes in interleukin-10 (IL-10) in pg/ml.

Measure: The mean change in serum interleukin-10 (IL-10).

Time: up to 4 weeks.

Description: Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.

Measure: The mean change in serum tumor necrosis factor-alpha (TNF alpha).

Time: up to 4 weeks.

Description: Recording the changes in immunoglobulin G (IgG) in ng/ml.

Measure: Mean changes in immunoglobulin G (IgG).

Time: up to 4 weeks.

Description: Recording the changes in immunoglobulin M (IgM) in ng/ml.

Measure: Mean changes in immunoglobulin M (IgM).

Time: up to 4 weeks.

Description: Recording the changes in PCR viral load in copies/mL.

Measure: The mean change in PCR viral load.

Time: up to 4 weeks.

Description: Recording the changes in lung CT.

Measure: Mean change in lung CT manifestation.

Time: up to 4 weeks.

Description: Recording any unexpected Adverse Events of the intervention.

Measure: Nature and severity of Adverse Events.

Time: up to 4 weeks.

Description: Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.

Measure: Time for lung recovery.

Time: up to 8 weeks.

Description: Recording the changes the event of missed drug doses.

Measure: The number of missed drug doses among each treatment group.

Time: up to 4 weeks.
107 Echocardiography in Patients With Covid-19 Undergoing Intensive Care Therapy

Prospective observational study of patients treated due to Covid-19 disease. Observation and analysis of echocardiographic studies performed in the intensive care setting.

NCT04412460
Conditions
  1. COVID
  2. ARDS, Human
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Measure: ICU Mortality

Time: up to 90 days

Secondary Outcomes

Measure: ICU length-of stay

Time: up to 90 days

Measure: ICU ventilator free days

Time: up to 90 days

Measure: Hospital length-of-stay

Time: up to 90 days
108 Mesenchymal Stem Cells for the Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID-19. Pilot Study

Acute Respiratory Distress Syndrome (ARDS) is the main cause of death from COVID-19. One of the main mechanisms for ARDS is the violent storm of cytokines and chemokines, which cause uncontrolled fatal systemic inflammation by the immune system on the body, with additional multiple organ failure. Mortality in cases of severe ARDS caused by COVID 19 varies significantly between 50 and 90%, basically depending on the age of the patient and the presence of comorbidities. The plasticity of Mesenchymal Stem Cells (MSC) regulates inflammation and immunity. MSC can promote and inhibit an immune response, depending on the dynamics of inflammation and depending on the activation force of the immune system, the types of inflammatory cytokines present, and the effects of immunosuppressants. Essentially, the state of inflammation determines the immunoregulatory fate of MSC. Thus, IV application of AMSCa has been shown to control the inflammatory response in various diseases, such as the graft-versus-host reaction and the ARDS caused by H5NI. The objective of this study is to describe the clinical changes secondary to IV administration of MSC allogenic, in patients with bilateral COVID-19 pneumonia complicated by severe ARDS, with the evaluation of the PaO2 / FiO2 ratio, heart and respiratory rates, and the fever curve. Five patients, of either sex, over 18 years of age, with bilateral pneumonia caused by COVID-19 and severe SIRA that has not improved with the standard management measures used at that time in the care center, will be included in the study. This treatment will be administered after discussing it with the relatives that it is a procedure considered as rescue and will be carried out with informed consent. 1x10(6) xKg will be applied IV. The follow-up of the patient will be for three weeks. PaO2 / FiO2 data, fever, inflammatory markers and immunity will be evaluated. The results will be compared with the historical controls attended at INCMNSZ.

NCT04416139
Conditions
  1. Covid 19
Interventions
  1. Biological: Infusion IV of Mesenchymal Stem cells
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the PaO2 / FiO2 ratio.

Measure: Functional Respiratory changes: PaO2 / FiO2 ratio

Time: Three weeks

Description: To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the heart rate per minute.

Measure: Clinical cardiac changes: Heart rate per minute

Time: Three weeks

Description: To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the respiratory rate per minute.

Measure: Clinical Respiratory Changes: Respiratory rate per minute

Time: Three weeks

Description: To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the fever curve in degrees centigrade.

Measure: Changes in body temperature

Time: Three weeks

Secondary Outcomes

Description: To assess the effect of the proposed treatment on the total Leukocytes

Measure: General biochemical changes in Leukocytes

Time: Three weeks

Description: To assess the effect of the proposed treatment on absolute lymphocytes

Measure: General biochemical changes on lymphocytes

Time: Three weeks

Description: To assess the effect of the proposed treatment on total platelets

Measure: General biochemical changes on platelets

Time: Three weeks

Description: To assess the effect of the proposed treatment on serum fibrinogen

Measure: General biochemical changes on fibrinogen

Time: Three weeks

Description: To assess the effect of the proposed treatment on procalcitonin

Measure: General biochemical changes on pocalcitonin

Time: Three weeks

Description: To assess the effect of the proposed treatment on ferritin

Measure: General biochemical changes on ferritin

Time: Three weeks

Description: To assess the effect of the proposed treatment on D-dimer

Measure: General biochemical changes on D-dimer

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of C-reactive protein

Measure: Changes on inflammatory C-reactive protein

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of TNFa in plasma.

Measure: Cahnges on Inflammatory cytokine TNFa

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of IL10 in plasma.

Measure: Changes on Inflammatory cytokine IL10

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of IL1 in plasma.

Measure: Changes on Inflammatory cytokine IL1

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of IL6 in plasma.

Measure: Changes on Inflammatory cytokine IL6

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of IL17 in plasma

Measure: Changes on Inflammatory cytokine IL 17

Time: Three weeks

Description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of VEGF in plasma

Measure: Changes on VEGF

Time: Three weeks

Description: Assess the radiological evolution of the proposed treatment through simple chest CT

Measure: Radiological Changes

Time: Three weeks

Description: Evaluate immune system improvement with mass cytometry to analyze patients' immune cells: regulatory T cells

Measure: Immunological changes on T cell

Time: Three weeks

Description: Evaluate immune system improvement with mass cytometry to analyze patients' immune cells: dendritic cells

Measure: Immunological changes on Dendritic cells

Time: Three weeks

Description: Evaluate immune system improvement with mass cytometry to analyze patients' immune cells: CD4 + T

Measure: Immunological changes on CD4+ T

Time: Three weeks

Description: Evaluate immune system improvement with mass cytometry to analyze patients' immune cells: CD8 + T

Measure: Immunological changes on CD8+ T

Time: Three weeks

Description: Evaluate immune system improvement with mass cytometry to analyze patients' immune cells: NK cells

Measure: Immunological changes on NK cell

Time: Three weeks

Description: Evaluate the safety of the proposed treatment (allergic reactions and / or infection)

Measure: Adverse events

Time: Three weeks

Description: To assess the negativization of the SARS-Cov2 PCR RNA detection test

Measure: RNA detection by SARS-Cov2 PCR

Time: Three weeks
109 Influence of External Dead Space on Volumetric Capnography Derived Parameters in Mechanically Ventilated COVID-19 Patients

The objective is to investigate the efficacy of volumetric capnography to detect changes in dead space, CO2 elimination and shape factor parameters before and after disconnection of external dead space in ventilated COVID-19 patients.

NCT04424082
Conditions
  1. Coronavirus
  2. ARDS, Human
Interventions
  1. Other: Removal of dead space filter
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: VCO2 is expected to increase after removal of the external dead space

Measure: change in carbon dioxide elimination (VCO2) i.e. ml CO2 eliminated/minute

Time: 60 minutes

Secondary Outcomes

Description: Removing the external dead space is expected to decrease alveolar dead space (ml)

Measure: Changes in alveolar dead space (a Vcap derived parameter)

Time: 60 minutes

Description: Removal of external dead space is expected to decrease PaCO2 (kPa).

Measure: Changes in arterial carbon dioxide tension (PaCO2).

Time: 60 minutes
110 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
111 Physical Rehabilitation in Intensive Care Unit in Acute Respiratory Distress Syndrome Patients With COVID-19

The primary aim of this study is to evaluate the effect of physical rehabilitation performed in intensive care unit on the range of joint motions and muscle strength of survivors following discharge from intensive care unit in patients with COVID-19. Secondary outcome is to assess the duration of mechanical ventilation, length of stay in intensive care unit and in hospital, and mortality rates during intensive care unit stay and health related quality of life following discharge in survivors. Until April 14 patients were provided all the intensive care managements except for rehabilitation and patients discharged before this time constituted the 'non-rehabilitation' group (n=17). Patients discharged after April 14 were provided rehabilitation in addition to usual intensive care unit care and constituted the study 'rehabilitation' group (n=18). Passive range of motion exercises to each joint and neuromuscular electrical stimulation to bilateral quadriceps and tibialis anterior muscles were applied 6 days/week in the 'rehabilitation' group during intensive care unit stay.

NCT04435080
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Rehabilitation
  4. Intensive Care Unit Acquired Weakness
  5. Critical Illness Polyneuromyopathy
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome Critical Illness

Primary Outcomes

Description: Hand grip strength is an indicator of overall muscle strength that predicts mortality in older patients. Handgrip strength was measured using a handheld dynamometer according to the instructions of the American Society of Hand Therapists.Patients were seated placing their arms by their sides with the elbow flexed to 90°, the forearm mid-prone, and the wrist in neutral position. Patients were asked to grip the dynamometer with maximal effort using standard verbal encouragement. Three trials were performed in the dominant hand with a 30 sec rest between trials and the highest value was recorded in kg. The cut-off values of grip strength is 28.6 kg in men and 16.4 kg in women. The measurement was performed 1 month after discharge.

Measure: Hand grip strength

Time: 1 month after discharge from hospital

Secondary Outcomes

Description: Short form - 36 measures health related quality of life. It is a self-reported survey that evaluates individual health status with eight parameters consisting of physical function, pain, role limitations attributed to physical problems, role limitations attributed to emotional problems, mental health, social functioning, energy/ vitality, general health perception. There is not a summary score, each section is scored between 0-100, 0 indicates the worst condition, 100 indicates the best. The measurement was performed 1 month after discharge.

Measure: Short form - 36

Time: 1 month after discharge from hospital

Description: Number of days of stay in intensive care unit from admission to discharge

Measure: Length of stay in intensive care unit

Time: through study completion, an average of 3 months

Description: Number of days of stay in hospital from admission to hospital to discharge from hospital

Measure: Length of stay in hospital

Time: through study completion, an average of 3 months

Description: Number of days of invasive mechanical ventilation during intensive care unit

Measure: Duration of invasive mechanical ventilation

Time: through study completion, an average of 3 months

Description: Manual muscle strength was graded via a composite of Medical Research Council Scale score which has an excellent inter-rater reliability in survivors of critical illness. This scale range from 0 point (no muscle contraction) to 5 points (normal muscle strength). Through examination of 3 muscle groups in each limb (arm abduction, forearm flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion), clinical important muscle weakness has been defined as a composite score < 48 out of maximum 60 points. The measurement was performed 1 month after discharge.

Measure: Manual muscle strength

Time: 1 month after discharge from hospital

Description: Range of joint motion was evaluated in upper and lower extremity joints by physical examination and the results were recorded as normal or restricted for each joint. The measurement was performed 1 month after discharge.

Measure: Range of joint motion

Time: 1 month after discharge from hospital
112 Assessment of the Effectiveness of Vibroacoustic Therapy for Respiratory Failure Caused by COVID 19

Vibroacoustic pulmonary therapy in patients with COVID19 is believed to have a positive effect on oxygen status and a decrease in the duration of respiratory failure

NCT04435353
Conditions
  1. Respiratory Distress Syndrome
  2. Hypoxemia
Interventions
  1. Device: VibroLUNG
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Hypoxia
HPO:Hypoxemia

Primary Outcomes

Description: Regression of respiratory failure under the influence of vibroacoustic therapy

Measure: Recovery respiratory fail

Time: 5-7 days
113 Effectiveness of Convalescent Immune Plasma Therapy in Severe COVID-19 Patients With Acute Respiratory Distress Syndrome

The aim of the study is to evaluate the safety, improvement of clinical symptoms and laboratory parameters of convalescent immune plasma treatment in severe Covid-19 patients with ARDS.

NCT04442958
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Other: Convalescent Immune Plasma
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Acute phase reactant

Measure: Plasma ferritin level

Time: 7. day

Description: Infection markers

Measure: Lymphocyte count

Time: 7. day

Description: Hypercoagulability

Measure: D-Dimer level

Time: 7. day

Description: Infection markers

Measure: C-Reactive protein level

Time: 7. day

Description: Infection markers

Measure: Plasma procalcitonin level

Time: 7. day

Description: Coagulopathy

Measure: Plasma fibrinogen level

Time: 7. day

Secondary Outcomes

Description: Arterial oxygenation

Measure: Fractional Inspired Oxygen Level

Time: 7. day

Description: Arterial oxygenation

Measure: Partial Oxygen Saturation level

Time: 7. day

Description: Arterial oxygenation

Measure: Arterial Oxygen level

Time: 7. day
114 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.
115 PROSAIC-19 - Prospective Longitudinal Assessment in a COVID-19 Infected Cohort

DESIGN Longitudinal prospective observational multicentre study. Primary objective: Understand the immune mechanisms driving COVID-19 disease in patients with a history of lung disease

NCT04444609
Conditions
  1. COVID-19
  2. SARS-CoV 2
  3. ARDS, Human
  4. Immune System Disorder
Interventions
  1. Other: Blood tests sputum, nasal lavage and brushing
MeSH:Respiratory Distress Syndrome, Adult Immune System Diseases

Primary Outcomes

Description: Anti-viral cytokine protein concentration in blood samples by ELISA

Measure: Anti-viral cytokine levels in blood samples in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Inflammatory cytokine protein concentration in sputum samples by ELISA

Measure: Anti-viral cytokines profiles within sputum samples in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Inflammatory cytokine protein concentration in nasal lavage samples by ELISA

Measure: Anti-viral cytokine profiles within nasal lavage samples in chronic respiratory disease associated with susceptibility to severe COVID-19 infection associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Inflammatory gene expression in upper airway respiratory epithelial cells by RNA sequencing.

Measure: Expression of inflammatory gene expression in upper respiratory epithelial airway cells using nasal brush specimens in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Secondary Outcomes

Description: Analysis of viral components recognized by the adaptive immune system

Measure: Identify the T cell antigens and B cell epitopes in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Cytokine protein concentration following PBMC stimulation to pathogen recognition receptor agonists by Elispot

Measure: Peripheral blood mononuclear cell (PBMC) interferon mediated immune responses to pathogen recognition receptor agonists in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Analysis of endothelial function

Measure: Identify endothelial function in chronic respiratory disease associated with susceptibility to severe COVID-19 infection using EndoPAT testing

Time: Through study completion an average of 1 year

Description: Serum and plasma protein concentration of endothelial cell inflammation biomarkers by ELISA

Measure: Endothelial cell inflammation biomarkers in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Analysis of sputum microbiome

Measure: Identify sputum 16S rRNA and ITS sequences in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Analysis of nasal microbiome

Measure: Identify nasal lavage 16S rRNA and ITS sequences in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year

Description: Study participant survey

Measure: Identify quality of life markers in chronic respiratory disease associated with susceptibility to severe COVID-19 infection

Time: Through study completion an average of 1 year
116 Inhaled Iloprost for the Treatment of Suspected COVID-19 Respiratory Failure

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by the rapid onset of widespread inflammation in the lungs. ARDS is thought to be the main cause of respiratory failure in COVID-19 patients. Research is still ongoing to further elucidate the different ARDS subtypes that may exist in COVID-19. It is crucial to find new targets for treatment and support of COVID-19 patients with respiratory failure.

NCT04445246
Conditions
  1. COVID-19
  2. ARDS, Human
  3. Hypoxemic Respiratory Failure
Interventions
  1. Drug: Inhaled ILOPROST
MeSH:Respiratory Insufficiency Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: change in oxygen saturation and PaO2/FiO2 ratio by 20% on day 6 compared to baseline values prior to Iloprost initiation.

Measure: change in oxygenation parameters

Time: 5 days

Secondary Outcomes

Description: likelihood to require intubation in the cohort treated with Iloprost

Measure: Rates of endotracheal intubation

Time: 28 days

Description: in days in the cohort treated with Iloprost

Measure: Invasive ventilation duration

Time: 28 days

Description: in days in the cohort treated with Iloprost

Measure: ICU length of stay

Time: 28 days

Description: in days in the cohort treated with Iloprost

Measure: Hospital Length of stay

Time: 28 days

Description: likelihood to require proning in the cohort treated with Iloprost

Measure: Rates of proning therapy

Time: 28 days

Description: likelihood to require ECMO cannulation in the cohort treated with Iloprost

Measure: Rates of ECMO cannulation

Time: 28 days

Description: likelihood to die of any cause within 28 days of initial hospital presentation

Measure: Mortality

Time: 28 days
117 Mesenchymal Stromal Cell Therapy For The Treatment Of Acute Respiratory Distress Syndrome Validation of Mechanistic Pathways and Clinical Efficacy

This is an open label, dose escalating safety study of the advanced therapy investigational medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed with SARS-CoV-2-induced severe acute respiratory distress syndrome (ARDS), according to the Berlin Definition, and who are on respirator/ventilator (used synonymously in this protocol) support due to respiratory insufficiency with or without concomitant circulatory problems, will be included and treated with a single dose of KI-MSC-PL-205.

NCT04447833
Conditions
  1. ARDS, Human
  2. COVID
Interventions
  1. Drug: Mesenchymal Stromal Stem Cells - KI-MSC-PL-205
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The incidence of pre-specified treatment related adverse events of interest (TRAEIs) occurring during the 10 days interval beginning with the start of the ATIMP infusion: New ventricular tachycardia, ventricular fibrillation or asystole within 10 days after infusion New cardiac arrhythmia requiring cardioversion within 10 days after infusion Clinical scenario consistent with transfusion incompatibility or transfusion-related infection within 10 days after infusion Thromboembolic events (e.g. Pulmonary embolism) within 10 days after infusion Cardiac arrest or death within 10 days after infusion

Measure: The incidence of pre-specified treatment related adverse events of interest (TRAEIs).

Time: From drug administration to day 10 post-infusion

Secondary Outcomes

Description: All-cause mortality at 60 days and then annually

Measure: Safety; All-cause mortality

Time: 60 days post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the leucocyte Count (number/L)

Measure: Changes in Leucocytes

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the trombocyte Count (number/L)

Measure: Changes in Trombocytes

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of CRP (mg/L)

Measure: Changes in plasma concentration of C-reactive protein (CRP)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of PK (INR)

Measure: Changes in plasma concentration of Prothrombin complex (PK)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of creatinine (μmol/L)

Measure: Changes in plasma concentration of Creatinine

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ASAT (μkat/L)

Measure: Changes in plasma concentration of Aspartate amino transferase (ASAT)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of ALAT (μkat/L)

Measure: Changes in plasma concentration of Alanine amino transferase (ALAT)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in the plasma concentration of NT-proBNP (ng/L)

Measure: Changes in plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in blood pressure (mmHg)

Measure: Changes in Blood pressure

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in body temperature (°C)

Measure: Changes in Body temperature

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in pulmonary compliance (dynamic and static) until day 10 post-infusion

Measure: Efficacy; Changes in pulmonary compliance

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in driving pressure (Plateau pressure- PEEP) until day 10 post-infusion

Measure: Efficacy; Changes in driving pressure (Plateau pressure- PEEP)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion

Description: Changes from baseline (Day 1; prior to administration of ATIMP) in oxygenation (PaO2/FiO2) until day 10 post-infusion

Measure: Efficacy; Changes in oxygenation (PaO2/FiO2)

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion

Description: Number of days with ventilator support

Measure: Efficacy; Duration of ventilator support

Time: Baseline (pre-infusion),day 1, 2, 3, 4, 7, 10 and 60 post-infusion

Description: Changes in amount of pulmonary bilateral infiltrates assessed by pulmonary X-ray from baseline (Day 1; prior to administration of ATIMP) until day 60

Measure: Efficacy; Pulmonary bilateral infiltrates

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes in Sequential Organ Failure Assessment (SOFA) score from baseline (Day 1; prior to administration of ATIMP) and during the ICU-period

Measure: Efficacy; Sequential Organ Failure Assessment (SOFA) score

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, end of ICU

Description: Duration of ICU stay and hospital stay (number of days; whole hospital period + calculated from Day 1)

Measure: Efficacy; Hospital stay

Time: Day 60 post-infusion

Description: Recovery of lung function assessed by Spirometry (FEV1, Vital Capacity) at day 60 and then annually

Measure: Lung function

Time: Day 60 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: To assess development of lung fibrosis using the HRCT Fibrosis Score using Computed tomography (CT) at baseline and on day 1, 3, 7, 10, end of ICU-residence, end of hospital stay, day 60, 6 month and 12 month and end of study (if possible during the infectious stage depending on hospital safety regimen during the pandemic).

Measure: Lung fibrosis

Time: Baseline (pre-infusion), day 1, 3, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Assessment of the patient's physical capacity by 6-Minute-Walk-Test (6MWT), starting at 6 months post Day 1 and then annually

Measure: Six minutes walk test

Time: 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Changes in Quality of Life by assessing the Short Form Health Survey (SF-36) score (starting at 6 months post Day 1 and then annually; patient reported outcome)

Measure: Changes in Quality of life

Time: 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Change in blood biomarkers related to the proposed mechanisms of action of KI-MSC-PL-205 in ARDS

Measure: Blood biomarkers

Time: Baseline (pre-infusion), day 1, 2, 3, 4, 7 and 10 post-infusion, 6 months, 1, 2, 3, 4 and 5 years post-infusion

Description: Sensitisation tests (test for donor-specific antibodies) against KI-MSC-PL-205 donor

Measure: Sensitisation test

Time: Baseline (pre-infusion), day 60 post-infusion
118 Knowledge, Attitude and Practice About COVID-19 and Awareness of Infection Control to Prevent COVID-19 Transmission in Clinics and Perception About Online Learning During Lock Down Period: A Cross-sectional Study

Coronavirus disease 2019 (abbreviated "COVID- 19") is a pandemic respiratory disease that is caused by a novel coronavirus and was first detected in December 2019 in Wuhan, China. The disease is highly infectious, and its main clinical symptoms include fever, dry cough, fatigue, myalgia, and dyspnoea.1 In China, 18.5% of the patients with COVID-19 developed to the severe stage, which is characterized by acute respiratory distress syndrome, septic shock, difficult-to-tackle metabolic acidosis, and bleeding and coagulation dysfunction. After China, COVID-19 spread across the world and many governments implemented unprecedented measures like suspension of public transportation, the closing of public spaces, close management of communities, and isolation and care for infected people and suspected cases. The Malaysian government had enforced Movement Control Order (MCO) from 18th March to 4th May 2020 and henceforth Conditional Movement Control Order (CMCO) until 9th June 2020. The battle against COVID-19 is still continuing in Malaysia and all over the world. Due to the CMO and CMCO in the country, public and private universities have activated the e-learning mode for classes and as the government ordered, universities are closed and no face-to-face activities allowed. This has forced students of all disciplines including dentistry to stay at home which are wide-spread across Malaysia and shift to e- learning mode. To guarantee the final success for fight against COVID-19, regardless of their education status, students' adherence to these control measures are essential, which is largely affected by their knowledge, attitudes, and practices (KAP) towards COVID-19 in accordance with KAP theory. Once the restrictions are eased students have to come back and resume their clinical work in the campus. Hence, in this study we assessed the Knowledge, Attitude, and Practice (KAP) towards COVID-19 and the students preference for online learning.

NCT04449081
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Corona Virus Infection
  3. Acute Lung Injury
  4. Fever
  5. Myalgia
  6. Cough
  7. Dyspnea
  8. Septic Shock
  9. Bleeding
Interventions
  1. Behavioral: Knowledge, Attitude, Practice, Awareness, Preference
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Myalgia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
HPO:Dyspnea Myalgia Respiratory distress

Primary Outcomes

Description: KAP towards COVID-19 was assessed using validated questionnnaire

Measure: Knowledge, Attitude, Practice of dental students towards COVID-19

Time: 4 months

Secondary Outcomes

Description: Awareness level about Infection control to prevent COVID-19 transmission in clinics was assesed using a standardized questionnaire

Measure: Awareness level about Infection control to prevent COVID-19 transmission in clinics

Time: 4 months

Description: Preference towards online learning. was assessed using a standard questionnaire

Measure: Preference towards online learning.

Time: 4 months
119 DSC-COVID-19: An Open-label Study on the Safety and Efficacy of Decidual Stromal Cells in Respiratory Failure Induced by COVID-19

This is a research study to see how safe and effective decidual stromal cells are in treating patients with respiratory failure (breathing problem where not enough oxygen is passed from the lungs into the blood) caused by COVID-19.

NCT04451291
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Decidual Stromal Cells (DSC)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury

Primary Outcomes

Measure: Number of ventilator free days following infusion of decidual stromal cells

Time: 28 days

Secondary Outcomes

Measure: Mortality rate from COVID-19

Time: 28 days

Measure: Mortality rate from COVID-19

Time: 60 days

Measure: Mortality rate from COVID-19

Time: 180 days

Measure: All-cause morality rate

Time: 28 days

Measure: All-cause morality rate

Time: 60 days

Measure: All-cause morality rate

Time: 180 days

Measure: Average number of days in ICU

Time: 180 days

Measure: Average number of days of hospital admittance

Time: 180 days

Measure: Average days not requiring vasopressors

Time: 180 days

Measure: Overall survival rate

Time: 180 days

Measure: Average viral clearance

Time: 180 days

Measure: Average number of days of supplemental oxygenation

Time: 180 days

Measure: Average number of day without supplemental oxygen

Time: 180 days

Measure: Mean PaO2/FiO2 as compared to patient baseline

Time: 180 days
120 A Phase 1/2a Study of the Safety and Efficacy of BX-U001 for the Treatment of Severe COVID-19 Pneumonia With Moderate to Severe Acute Respiratory Distress Syndrome (ARDS).

This is a phase 1/2a study including 2 parts, phase 1 and phase 2a. The phase 1 part is an open-label, single-arm, dose-escalating study to evaluate the safety and explore the dose limiting toxicity and maximum tolerated dose of a human umbilical cord derived mesenchymal stem cell product (BX-U001) in severe COVID-19 pneumonia patients with acute respiratory distress syndrome (ARDS). Qualified subjects after the screening will be divided into low, medium, or high dose groups to receive a single intravenous infusion of BX-U001 at the dose of 0.5×10^6, 1.0×10^6, or 1.5×10^6 cells/kg of body weight, respectively. The Phase 2a part is a randomized, placebo-controlled, double-blind clinical trial examining the safety and biological effects of BX-U001 at the appropriate dose selected from phase 1 for severe COVID-19 pneumonia patients with the same inclusion/exclusion criteria as the phase 1 part.

NCT04452097
Conditions
  1. COVID-19
  2. ARDS
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: Human umbilical cord mesenchymal stem cells + best supportive care
  2. Other: Placebo control + best supportive care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Safety will be defined by the incidence of infusion-related adverse events as assessed by the treating physician

Measure: Incidence of infusion-related adverse events

Time: Day 3

Description: Safety will be defined by the incidence of TEAEs and TESAEs as assessed by the treating physician

Measure: Incidence of any treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)

Time: Day 28

Secondary Outcomes

Description: The dose will be selected based on the assessment of dose-limiting toxicity and maximum tolerated dose.

Measure: Selection of an appropriate dose of BX-U001 for the following Phase 2 study

Time: Day 28

Measure: All-cause mortality

Time: Day 28

Description: 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 low flow 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 required ongoing medical care 7. Not hospitalized.

Measure: Proportion of patients achieving clinical response by the improvement of at least 2 points on the 7-point ordinal scale.

Time: Day 14

Measure: Duration of ICU stay

Time: Day 28

Measure: Duration of hospital stay

Time: Day 28

Measure: Changes in blood cytokine levels

Time: Day 28
121 Tissue Plasminogen Activator (tPA) Treatment for an Atypical Acute Respiratory Distress Syndrome (Microvascular COVID-19 Lung Vessels Obstructive Thromboinflammatory Syndrome (MicroCLOTS): A Multicentral Randomized Trial (AtTAC-trial)

At the beginning COVID-associated lung injury was considered as typical ARDS, hence respiratory and nonrespiratory treatments were delivered according to general principles for this kind of illness. There is hypothesis that in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. The investigators suggest that thrombolytic therapy may be beneficial when compared to standard care in patients with SARS-CoV-2 and severe respiratory failure.

NCT04453371
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Tissue plasminogen activator
  2. Drug: Ringer solution
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: P/F (PaO2/FiO2) change during the first 72hrs after the end of the procedure in adult patients with severe atypical ARDS caused by SARS-2-CoV.

Time: Each 6 hours during first 3 days after the end of thrombolysis procedure.

Secondary Outcomes

Description: Calculated as 28 days - number of days when patient receive any kind of ventilatory support (MV + SV + NIV).

Measure: Ventilator-free time (days free from MV) for 28 days of observation.

Time: 28 days

Other Outcomes

Measure: Mortality in 28 days and 1 year after randomization despite of the reason.

Time: 28 days, 1 year after randomization

Description: Number of days when patient was in ICU

Measure: Length of stay in the ICU

Time: 28 days

Description: Number of days when patient was in hospital

Measure: Length of stay in hospital

Time: 28 days

Measure: The time needed for "improvement of 2 points" according to WHO "Ordinal Scale for Clinical Improvement"

Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 month

Measure: Chest radiographs on a daily basis and define barotrauma as the presence of new pneumothorax, pneumomediastinum, pneumoperitoneum, or subcutaneous emphysema.

Time: Daily up to extubation than once a week/or on attending intensivist's discretion up to 1 month

Measure: Blood Pressure in millimetres of mercury

Time: Each 4 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: Heart Rate in beats per minute

Time: Each 4 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: Blood Oxygen Saturation

Time: Each 4 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: ECG Q-wave

Time: Each 24 hours during first 2 weeks after the end of thrombolysis procedure.

Measure: ECG ST-segment

Time: Each 24 hours during first 2 weeks after the end of thrombolysis procedure.
122 A Study of Mesenchymal Stem Cells as a Treatment in Patients With Acute Respiratory Distress Syndrome Caused by COVID-19

This is a pilot phase, open label, non-randomized study for the treatment of ARDS in patients infected with COVID-19. Subjects will be enrolled and treated with one dose of mesenchymal stem cells and follow-up will occur 90 days post-treatment.

NCT04456361
Conditions
  1. ARDS, Human
  2. Covid-19
Interventions
  1. Biological: Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Number of patients with changes in percentage of resting Oxygen saturation (%O2)

Measure: Oxygen saturation

Time: Baseline, and at days 2, 4 and 14 post-treatment

Secondary Outcomes

Description: Changes in mmHg of Arterial partial pressure of oxygen / Fraction of inspiration O2 (PaO2/FiO2) in all participants

Measure: Oxygen pressure in inspiration

Time: Baseline, and at days 2, 4 and 14 post-treatment

Description: Changes in percentage of participants with reduction in bilateral ground-glass opacities

Measure: ground-glass opacity

Time: Baseline, and at day 14 post-treatment

Description: Changes in percentage of participants with reduction of pneumonia bilateral infiltration

Measure: Pneumonia infiltration

Time: Baseline, and at day 14 post-treatment

Description: Number of participants with a reduction in Lactate dehydrogenase (mg/dL)

Measure: Lactate dehydrogenase

Time: Baseline, and at days 4 and 14 post-treatment

Description: Number of participants with a reduction in C-reactive protein (mg/dL)

Measure: C-reactive protein

Time: Baseline, and at days 4 and 14 post-treatment

Description: Number of participants with a reduction in D-dimer (mg/dL)

Measure: D-dimer

Time: Baseline, and at days 4 and 14 post-treatment

Description: Number of participants with a reduction in Ferritine (mg/dL)

Measure: Ferritine

Time: Baseline, and at days 4 and 14 post-treatment
123 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
124 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
125 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)
126 Feasibility and Physiological Effects of a Postural Recruitment Maneuver in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 Infection

The purpose of this study is to evaluate if a postural recruitment maneuver (PRM) improves the aeration and distribution of lung ventilation in patients with Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 infection; without the need to reach high airway pressures as in the standard lung recruitment maneuver and / or place the patient in prone position. This strategy could be particularly useful in the context of a major health emergency in centers with limited resources.

NCT04475068
Conditions
  1. Sars-CoV2
  2. ARDS
Interventions
  1. Procedure: Lateral Position (left and right lateral decubitus)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Lung aeration measured by ultrasound reaeration score, ranges from 0 (all regions are well aerated) to 36 (all regions are consolidated).

Measure: Effects of a postural recruitment maneuver in lung aeration

Time: Through study completion (up to 24 hours)

Description: Distribution of ventilation measured by EIT (distribution and changes in the impedance in AU, arbitray units)

Measure: Effects of a postural recruitment maneuver in distribution of ventilation

Time: Through study completion (up to 24 hours)

Description: Gas exchange measured by blood gas analysis (PaO2, PaCO2, in mmHg) and capnography (end-tidal CO2, in mmHg)

Measure: Effects of a postural recruitment maneuver in gas exchange

Time: Through study completion (up to 24 hours)

Description: Respiratory mechanics measured by esophageal balloon (esophageal pressure, transpulmonary pressure, in cmH2O)

Measure: Effects of a postural recruitment maneuver in respiratory mechanics

Time: Through study completion (up to 24 hours)

Description: Hemodynamic data measured by invasive arterial monitoring (mean arterial pressure, in mmHg)

Measure: Effects of a postural recruitment maneuver in hemodynamic

Time: Through study completion (up to 24 hours)

Secondary Outcomes

Description: Oxigenatory tolerance evaluated with pulse oximeter (arterial oxygen saturation, in percentage)

Measure: Feasibility of a postural recruitment maneuver

Time: Through study completion (up to 24 hours)
127 Interventional, Open, Non-comparative, Multicenter Study to Assess the Safety and Effectiveness of the Use of the MakAir Artificial Ventilator in the Expected Situation of a Shortage of Technical Devices for Invasive Mechanical Ventilation, Linked to the Coronavirus COVID-19

The objective of our study is to carry out an evaluation of the safety and the effectiveness of the use of the MakAir respirator as useful supplement in situation of shortage of technical devices of assistance to the mechanical invasive ventilation, related to COVID-19 through a protocol in 3 successive sequences.

NCT04475185
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Device: MakAir
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Number of dysfunctions which can lead to or have led to "respiratory" adverse events or to serious adverse events (SAE)

Measure: Number of dysfunctions

Time: 24 hours for sequence 1

Description: Number of dysfunctions which can lead to or have led to "respiratory" adverse events or to serious adverse events (SAE)

Measure: Number of dysfunctions

Time: 5 days for sequence 2

Description: Number of dysfunctions which can lead to or have led to "respiratory" adverse events or to serious adverse events (SAE)

Measure: Number of dysfunctions

Time: 10 days for sequence 3
128 A Multi-Centre, Open Label, Two Arm Randomized, Pivotal Phase 2 Trial to Study the Efficacy and Safety of Itolizumab in COVID-19 Complications

Randomized, Parallel Group, Active Controlled Trial

NCT04475588
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Cytokine Release Syndrome
  3. Covid19
Interventions
  1. Drug: Itolizumab IV infusion
  2. Drug: Best supportive care" which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: 1-month mortality is defined as the ratio of patients who will live after 1 month from study start out of those registered at baseline

Measure: One-month mortality rate between the two arms

Time: One-month

Secondary Outcomes

Description: Baseline, during treatment, One month

Measure: Biomarkers (IL-6, TNF-a, IL1, IL17, etc…)

Time: One Month

Description: Baseline, during treatment (Before every dose and 12 h post dose) up to 1 month

Measure: Lymphocyte count

Time: One Month

Description: Baseline, during treatment (Before every dose and 12 h post dose) up to 1 month

Measure: CRP (C-reactive protein) level

Time: One Month

Description: Baseline, during treatment (Before every dose and 12 h post dose) up to 1 month

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

Time: One Month

Description: At baseline, after seven days and if clinically indicated (up to 1 month)

Measure: Radiological response

Time: one month

Description: from baseline up to patients discharge (up to 1 month)

Measure: Duration of hospitalization

Time: One Month

Description: up to 1 month

Measure: Remission of respiratory symptoms

Time: One Month
129 Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19)

The purpose of this study is to evaluate the efficacy of vadadustat for the prevention and treatment of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus Disease 2019 (COVID-19).

NCT04478071
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Coronavirus Infection
Interventions
  1. Drug: vadadustat
  2. Drug: placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS): 8 - Death 7 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 6 - Hospitalized, on non-invasive ventilation or high flow oxygen devices 5 - Hospitalized, requiring supplemental oxygen 4 - Hospitalized, not requiring supplemental oxygen - requiring ongoing care (COVID-19 related or otherwise) 3 - Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 2 - Not hospitalized, limitation on activities and/or requiring home oxygen 1 - Not hospitalized, no limitations on activities

Measure: Number of participants who are classified 8 (dead), 7 (hospitalized, on invasive mechanical ventilation or ECMO), or 6 (hospitalized, on non-invasive ventilation or high flow oxygen devices) on the NIAID ordinal scale

Time: day 14

Secondary Outcomes

Description: Modified Sequential Organ Failure Assessment (MSOFA) scale: Each of 5 organ systems is given a score of 0 to 4, as detailed below. The MSOFA scale total score is the sum of the score for the 5 organ systems. Discharged patients will be assigned a score of 0 and dead patients a score of 20. Respiratory oxygen saturation(SpO2)/concentration of oxygen that a person inhales(FiO2): 0 (> 400); 1 (≤ 400); 2 (≤ 315); 3 (≤ 235); 4 (≤ 150) Liver: 0 (No scleral icterus or jaundice); 3 (Scleral icterus or jaundice) Cardiovascular, hypotension: 0 (No hypotension); 1 (MAP < 70 mm Hg); 2 (Dopamine ≤ 5 or dobutamine any dose); 3 (Dopamine > 5, Epinephrine ≤ 0.1, Norepinephrine ≤ 0.1); 4 (Dopamine > 15, Epinephrine > 0.1, Norepinephrine > 0.1) Central Nervous System (CNS), Glasgow Coma Score: 0 (15), 1 (13 - 14); 2 (10 - 12); 3 (6 - 9); 4 (< 6) Renal, Creatinine mg/dL: 0 (< 1.2); 1 (1.2 - 1.9); 2 (2.0 - 3.4); 3 (3.5 - 4.9); 4 (> 5.0)

Measure: Number of participants with a total score of 0 on the Modified Sequential Organ Failure Assessment (MSOFA) scale

Time: day 14
130 Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.

NCT04482712
Conditions
  1. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  2. Respiratory Failure
  3. Sars-CoV2
Interventions
  1. Drug: Rapamycin
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury Syndrome

Primary Outcomes

Description: The proportion of participants who survive without respiratory failure

Measure: Survival rate

Time: 4 weeks

Secondary Outcomes

Description: The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8

Measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale

Time: Baseline to 4 weeks

Description: An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)

Measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale

Time: Baseline to 4 weeks

Other Outcomes

Description: Total number of deaths during the study period

Measure: All cause mortality

Time: 4 weeks

Description: Number of days on ECMO

Measure: Duration of ECMO

Time: Up to 4 weeks

Description: Number of days participants are on supplemental oxygen

Measure: Duration of supplemental oxygen

Time: Up to 4 weeks

Description: Days of hospitalization

Measure: Length of hospital stay

Time: Up to 4 weeks

Description: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)

Measure: Length of time to SARS-CoV2 negativity

Time: Up to 4 weeks
131 Respiratory System Mechanics and Gas Exchange Characteristics Applying Different Ventilatory Strategies in Patients With SARS-CoV-2

The combination of different ventilatory strategies and its effects on respiratory mechanics and gas exchange in patients under mechanical ventilation with acute respiratory distress syndrome secondary to coronavirus-19 has been scarcely described.

NCT04486729
Conditions
  1. Covid19
  2. ARDS, Human
Interventions
  1. Other: High PEEP with end inspiratory pause
  2. Other: Low PEEP - FiO2 high
  3. Other: High PEEP without end inspiratory pause
  4. Other: Low PEEP - FiO2 low
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: The driving transpulmonary pressure will be evaluated between the high and low PEEP condition using the formula: driving transpulmonary pressure = driving airway pressure - driving esophageal pressure (cmH2O).

Measure: Driving transpulmonary pressure (cmH2O)

Time: 10 minutes

Description: The Bohr dead space fraction will be evaluated with high PEEP between the condition with end inspiratory pause and with no end inspiratory pause application using the formula: Bohr dead space fraction = Alveolar pressure of CO2 (PACO2) - Expired pressure of CO2 (PECO2) / PACO2

Measure: Bohr dead space fraction (%)

Time: 10 minutes

Description: The shunt fraction will be evaluated with low PEEP between the condition with high fraction of oxygen to achieve a saturation goal of 96-98% and the condition with low fraction of oxygen to achieve a saturation goal of 88-92%. The shunt fraction will be calculated using the formula: Qs/Qt = (capillary oxygen content - arterial oxygen content)/(capillary oxygen content - venous oxygen content)

Measure: Shunt fraction (%)

Time: 10 minutes
132 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
133 Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19) - COVEN Study

This is a prospective, randomized, single-center, open-label controlled trial, designed to compare the efficacy of two ventilation strategies (Low Tidal Volume and positive end-expiratory pressure (PEEP) based on the Acute Respiratory Distress Syndrome (ARDS) Network low PEEP-fraction of inspired oxygen inspired oxygen fraction (FIO2) Table versus Low Driving Pressure and PEEP guided by Electrical Impedance Tomography (EIT) in reducing daily lung injury score in patients with acute respiratory distress syndrome caused by COVID-19. The two strategies incorporate different prioritizations of clinical variables. The PEEP-FIO2 table strategy aims to reduce lung overdistension, even if it requires tolerating worse gas exchange. EIT-guided strategy prioritizes mechanical stress protection, avoiding alveolar overdistension and collapse.

NCT04497454
Conditions
  1. Respiratory Distress Syndrome
  2. Severe Acute Respiratory Syndrome Due to Coronavirus (SARS-CoV2)
  3. Mechanical Ventilation
Interventions
  1. Other: EIT-Group
  2. Other: ARDSNet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Syndrome

Primary Outcomes

Description: This score originally ranges from 0 to 4 points based on the average of 4 parameters (PaO2/FiO2, chest X-Ray, PEEP level, and Respiratory compliance). In the modified version, if the patient dies, he or she automatically receives a score of 5 irrespective of the other four parameters. If the patient is extubated, the score is automatically zero. We also substituted FiO2 for PEEP guaranteeing equivalence of the score when either the low or high PEEP-FiO2 table is applied.

Measure: Average daily Modified Lung injury score until day 28

Time: daily

Secondary Outcomes

Description: Number of days with less than or equal to 1 Liter/min of oxygen supplementation until day 28

Measure: High oxygen dependence free days until day 28

Time: 28 days

Description: Number of days free of mechanical ventilation assistance after protocol inclusion and before day 28

Measure: Mechanical ventilation free days until day 28

Time: 28 days

Description: Occurrence of shock (persistent hypotension despite rescue measures) and incidence of barotrauma

Measure: Incidence of shock or barotrauma

Time: 28 days

Description: Occurrence of acute renal failure that justifies renal replacement therapy

Measure: Incidence of acute renal failure requiring renal replacement therapy

Time: 28 days

Description: Percentage of patients who died in each arm up to 28 days

Measure: 28-day mortality

Time: 28 days
134 Multicenter, Open-label, Randomised Trial to Assess the Efficacy and Tolerability of Poractant Alfa(Porcine Surfactant, Curosurf®) in Hospitalized Patients With SARS-COV-19 Acute Respiratory Distress Syndrome (ARDS)

The purpose of this Phase II -Proof of Concept study is to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in adult hospitalized patients with SARS-COV-19 acute respiratory distress syndrome (ARDS)

NCT04502433
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: CUROSURF® (poractant alfa)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: The primary outcome variable will be the number of ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation during the 21 days following randomisation.

Measure: number of ventilator-free days

Time: up to 21 days

Secondary Outcomes

Measure: Number of free days from invasive ventilation

Time: up to 21 days

Measure: Number of free days from non-invasive ventilation (NIV)

Time: up to 21 days

Measure: Change from baseline in PaO2/FiO2 ratio measured at 6 hours and 12 hours following administration of each dose in the treated group and at the similar timepoints in the control group

Time: 6, 12, 30, 36, 54 and 60 hours after randomisation

Measure: Change from baseline in PaO2/FiO2 ratio at additional timepoints

Time: every 24 hours after treatment/randomisation until the patient is discharged from the ICU . Up to 28 days

Measure: Length of ICU stay (days)

Time: up to 28 days

Measure: Mortality at Day 28

Time: Day 28

Measure: Change from baseline in ventilatory parameter (Tidal volume (TV))

Time: up to 28 days

Description: min score 0 max score 24

Measure: Delta Sequential Organ Failure Assessment (SOFA) Score

Time: up to 28 days

Measure: Incidence of all the AEs, AEs related to poractant alfa (treated cohort) (ADRs), serious AEs (SAEs) and AEs leading to death

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (pH)

Time: up to 28 days

Measure: Percentage of patients with PaO2/ FiO2 improvement of >20% following administration of each dose in the treated group and at similar timepoints in the control group

Time: at 6 and 12 hours following administration each dose in the treated group and at similar timepoints in the control group = up to 60 hours after the randomization

Measure: Number of Extracorporeal Membrane Oxygenation (ECMO)-free days- (only for cohort 2 of patients in ECMO)

Time: 21 days after randomization

Measure: Change from baseline in FiO2

Time: (6, 12, 30, 36, 54 and 60 hours after randomisation + every 24 hours after treatment/randomisation until the patient is discharged from the ICU = up to 28 days

Measure: Change from baseline in ventilatory parameter (respiratory rate (RR))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (dynamic compliance (Cdyn))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (static compliance (Cstat))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP)

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP))

Time: up to 28 days

Measure: Change from baseline in ventilatory parameter (plateau pressure (Pplat))

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (pCO2)

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (pO2)

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (HCO3)

Time: up to 28 days

Measure: Change from baseline in blood gas analysis acid-base balance parameter (lactate)

Time: up to 28 days
135 Exhaled Breath Particles as a Clinical Indicator for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrom (ARDS) in COVID-19 Positive and Negative Patients

Acute Respiratory Distress Syndrome (ARDS) reflects the hallmark of the critical course of COVID19. We have recently shown that Exhaled Breath Particles (EBP) measured as particle flowrate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR increased before the cytokine storm. Early detection of ALI and ARDS is crucial for the patient's chance of survival as early treatment, such as preparing for intensive care, prone position and protective ventilation when the patient is treated in mechanical ventilation, can be implemented early in the process. In the present study we aim to use real time PFR as an early detector for COVID19 induced ARDS. We will also collect EBPs onto a membrane for subsequent molecular analysis. Previous studies have shown that most of those proteins found in broncho alveolar lavage (BAL) are also found in EBP. We therefore also aim to be able to diagnose COVID19 by analyzing EBP using PCR with the same specificity as PCR from BAL, but also to identify protein biomarkers for early detection of ARDS.

NCT04503057
Conditions
  1. Covid19
  2. ARDS, Human
  3. ALI
MeSH:Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Detect COVID-19 in EBP using RT-PCR

Measure: COVID-19 RT-PCR detection in EBP

Time: 12-36 months

Description: Detection of proteins biomarkers in EBP

Measure: Detection of proteins biomarkers in EBP

Time: 12-36 months

Description: We have recently shown that Exhaled Breath Particles (EBP) measured as particle flowrate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR increased before the cytokine storm. Early detection of ALI and ARDS is crucial for the patient's chance of survival as early treatment, such as preparing for intensive care, prone position and protective ventilation when the patient is treated in mechanical ventilation, can be implemented early in the process. In the present study we aim to use real time PFR as an early detector for COVID19 induced ARDS.

Measure: Particle flow rate as an early indicator for lung injury

Time: 12-36 months
136 Comparison of Extra Vascular Lung Water Index in Covid-19 ARDS and "Typical"ARDS Patients

Covid-19 also primarily affects endothelium that line up the alveoli. The resulting hypoxemia may differ from "typical" Acute Respiratory Distress Syndrome (ARDS) due to maldistribution of perfusion related to the ventilation. Thus, pathophysiology of Covid-19 ARDS is different, which requires different interventions than typical ARDS. The investigators will assess whether extravascular lung water index and permeability of the alveolar capillary differs from typical ARDS with transpulmonary thermodilution (TPTD) technique. Extravascular Lung Water Index (EVLWI) and Pulmonary Vascular Permeability Index (PVPI) will be compared.

NCT04508933
Conditions
  1. Respiratory Distress Syndrome, Adult
  2. Ventilation Perfusion Mismatch
  3. Pulmonary Edema
  4. Covid19
Interventions
  1. Device: Extravascular Lung Water Index
  2. Device: Pulmonary Vascular Permeability Index
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Pulmonary Edema Acute Lung Injury
HPO:Pulmonary edema

Primary Outcomes

Description: The amount of fluid accumulated in the lung measured by transpulmonary thermodilution (ml/kg)

Measure: Extravascular Lung Water Index

Time: 1 day

Description: Integrity of the alveolocapillary barrier measured by transpulmonary thermodilution

Measure: Pulmonary vascular permeability index

Time: 1 day
137 Effectiveness and Safety of Telmisartan in Acute Respiratory Failure Due to COVID-19

Rationale: The renin-angiotensin-aldosterone system (RAAS) dysregulation may play a central role in the pathophysiology of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection associated acute lung injury (ALI) / acute respiratory distress syndrome (ARDS). In the RAAS, Angiotensin I (Ang I) is converted to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). Ang II mediates vasoconstrictive, pro-inflammatory and pro-oxidative effects through agonism at Ang II type 1 receptor (AT1R). ACE2 converts Ang II to angiotensin 1-7 (Ang1-7), which finally binds to Mas receptor (MasR) and mediates many beneficial actions, including vasodilation and anti-inflammatory, anti-oxidant and antiapoptotic effects. ACE2, a homologue of ACE, is an integral cell membrane protein with a catalytic domain on the extracellular surface exposed to vasoactive peptides. SARS-CoV-2 penetrates the cell through ACE2, and the increase of this receptor (due to the use of ACE inhibitors or angiotensin receptor blockers [ARBs]) may facilitate SARS-CoV-2 infection, which might increase the risk of developing severe and fatal SARS-CoV-2 infection. However, through upregulation of ACE2, ACE inhibitors/ARBs can exert anti-inflammatory and antioxidative effects, which may be beneficial in preventing ALI and ARDS. Objective: To evaluate the effectiveness and safety of telmisartan in respiratory failure due to COVID-19. Study design: This is an open label, phase 2 clinical trial. Study population: Adult hospitalized SARS-CoV-2-infected patients (n=60). Intervention: The active-treatment arm will receive telmisartan 40 mg daily and the control arm will receive standard care. Treatment duration will be 14 days or up to hospital discharge <14 days or occurrence of the primary endpoint if <14 days. Main study endpoint: The primary study endpoint is the occurrence within 14 days of randomization of either: 1) Mechanical ventilation or 2) Death.

NCT04510662
Conditions
  1. COVID-19
  2. Respiratory Insufficiency
  3. Telmisartan
  4. Respiratory Distress Syndrome, Adult
Interventions
  1. Drug: Telmisartan
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Acute Lung Injury Pulmonary Valve Insufficiency
HPO:Pulmonary insufficiency

Primary Outcomes

Description: Death is defined as all-cause mortality

Measure: Death

Time: Within 30 days

Description: Occurrence of mechanical ventilation

Measure: Mechanical ventilation

Time: Within 14 days

Secondary Outcomes

Description: Defined as a 50% decline in estimated glomerular filtration rate relative to baseline, or decrease of >30 ml/min/1.73m2 and to a value below 60 ml/min/1.73m2

Measure: Occurrence of acute kidney injury

Time: Within 14 days

Description: Incidence of episodes of blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic

Measure: Incidence of hypotension

Time: Within 14 days

Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension

Measure: Incidence of hypotension requiring vasopressors

Time: Within 14 days

Description: Outcome reported as the number of participants in each arm who experience sepsis, defined as the presence of at least 2 of the following clinical criteria together (qSOFA score): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less

Measure: Incidence of Sepsis

Time: Within 14 days

Description: Hospital length of stay (days)

Measure: Hospital length of stay

Time: Within 14 days
138 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Dose Escalation and Proof-of-Concept Study to Evaluate the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Moderate to Severe Coronavirus Disease 2019 (COVID-19) (RESCUE Study)

This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter, dose escalation and proof of concept study to evaluate the safety and efficacy of razuprotafib subcutaneously administered three times daily (TID) in hospitalized subjects with moderate to severe COVID-19. Part 1 of the study is a 2-step dose escalation period conducted in approximately 60 subjects. Part 2 is a safety and efficacy period evaluating razuprotafib doses selected from Part 1 and will be conducted in approximately 120 subjects. Subjects will receive razuprotafib or placebo TID for 7 days or until discharge from the hospital (or death) and will be evaluated for safety and efficacy through Day 28. The effects of razuprotafib on biomarkers of coagulation, inflammation and vascular leakage will also be evaluated.

NCT04511650
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Razuprotafib Subcutaneous Solution
  2. Drug: Placebo Subcutaneous Solution
MeSH:Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Measure: Proportion of subjects alive and free of respiratory failure at Day 7

Time: Baseline up to Day 7

Measure: Proportion of subjects alive and free of respiratory failure at Day 28

Time: Baseline up to Day 28

Measure: Length hospitalized and free of respiratory failure from baseline to Day 7

Time: Baseline up to Day 7

Measure: Length hospitalized and free of respiratory failure from baseline to Day 28

Time: Baseline up to Day 28

Measure: Length of hospitalization from baseline to Day 7

Time: Baseline up to Day 7

Measure: Length of hospitalization from baseline to Day 28

Time: Baseline up to Day 28

Measure: Proportion of subjects who improve by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7

Time: Baseline up to Day 7

Measure: Proportion of subjects who improve by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 28

Time: Baseline up to Day 28

Measure: Proportion of subjects who worsen by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7

Time: Baseline up to Day 7

Measure: Proportion of subjects who worsen by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 28

Time: Baseline up to Day 28

Measure: All-cause mortality at Day 7

Time: Baseline up to Day 7

Measure: All-cause mortality at Day 28

Time: Baseline up to Day 28

Measure: Length of ICU stay from baseline to Day 28

Time: Baseline up to Day 28

Measure: Number of subjects in each category of the NIAID 8-point ordinal scale at Day 7

Time: Baseline up to Day 7

Measure: Number of subjects in each category of the NIAID 8-point ordinal scale at Day 28

Time: Baseline up to Day 28

Measure: Time to return to prehospitalization oxygen requirement

Time: Baseline up to Day 28

Measure: Proportion of subjects who were discharged and remained free of respiratory failure prior to Day 7

Time: Baseline up to Day 7

Measure: Proportion of subjects who were discharged and remained free of respiratory failure prior to Day 28

Time: Baseline up to Day 28

Measure: Change in PaO2:FiO2 ratio from baseline to Day 7

Time: Baseline up to Day 7

Measure: Change in PaO2:FiO2 ratio from baseline to Day 28

Time: Baseline up to Day 28

Secondary Outcomes

Measure: Number of participants with any serious adverse event from baseline to Day 7

Time: Baseline up to Day 7

Measure: Number of participants with any treatment emergent adverse event from baseline to Day 28

Time: Baseline up to Day 28

Measure: Number of participants with any treatment emergent adverse event from baseline to Day 7

Time: Baseline up to Day 7

Measure: Number of participants with any serious adverse event from baseline to Day 28

Time: Baseline up to Day 28

Other Outcomes

Measure: Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, Angpt 2, IL-6, IL-8, TNFα, HMGB-1, CRP and D-dimer);

Time: Baseline up to Day 7
139 Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Mechanical Ventilation in Ireland

Existing information suggests that a drug called heparin, given through a device called a nebuliser, will decrease severity of lung damage caused by COVID-19 who require the assistance of a ventilator to breathe. It is thought that heparin could do this through multiple mechanisms. The investigators will measure the effect with a marker called d-dimer, which is related to blood clotting, and monitor the safety of this treatment as one of the major outcomes for the study. The investigators will also assess clinical outcomes such as markers of oxygen levels, time to liberation from a ventilator in patients with COVID-19 lung disease, and functional outcomes at day 28 and 60 as secondary outcomes.

NCT04511923
Conditions
  1. Covid19
  2. ARDS, Human
  3. Lung Injury, Acute
  4. Ventilation Perfusion Mismatch
Interventions
  1. Drug: Nebulised heparin
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: Effect of nebulised heparin on d-dimer profile, assessed via d-dimer AUC and via a mixed effects model, with data collected on days 1, 3, 5 and 10.

Measure: D-dimer profile

Time: Up to day 10.

Description: Safety of nebulised heparin delivered by aerogen solo nebuliser in patients with COVID-19 induced severe respiratory failure, as measured by the incidence of severe adverse events.

Measure: Frequenccy of Severe Adverse Outcomes

Time: Up to day 60

Secondary Outcomes

Description: Determine the impact of nebulised heparin on oxygenation index

Measure: Oxygenation Index

Time: Up to day 10

Description: Effect of nebulised heparin on indices of inflammation (Interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1), C-reactive protein, procalcitonin, Ferritin,) will be assessed (AUC on days 1, 3, 5 and 10)

Measure: Indices of Inflammation

Time: Up to day 10

Description: Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed.

Measure: Ratios of Indices of Inflammation

Time: Up to day 10

Description: Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10).

Measure: Indices of Coagulation

Time: Up to day 10

Description: Determine the effect of nebulised heparin on Quasi-Static Lung Compliance (i.e. tidal volume/(Plateau pressure-PEEP) measured on days 1,3,5,10.

Measure: Quasi-Static Lung Compliance

Time: Up to day 10

Description: Time to separation from invasive ventilation, where non survivors are treated as though not separated from invasive ventilation.

Measure: Time to separation from invasive ventilation

Time: Up to day 28

Description: Number treated with neuromuscular blockers instituted after enrolment

Measure: Number treated with neuromuscular blockers

Time: Up to day 10

Description: Number treated with prone positioning instituted after enrolment

Measure: Number treated with Prone positioning

Time: Up to day 10

Description: Number treated with extra-corporeal membrane oxygenation instituted after enrolment

Measure: Number treated with extra-corporeal membrane oxygenation

Time: Up to day 10

Description: Number tracheotomised

Measure: Number requiring Tracheostomy

Time: Up to day 28

Description: Time to separation from invasive ventilation among survivors

Measure: Time to separation from invasive ventilation among survivors

Time: Up to day 28

Description: Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care

Measure: Discharge to ward

Time: Up to day 28

Description: Time to discharge from the ICU to day 28, among survivors

Measure: Discharge to ward in survivors

Time: Up to day 28

Description: Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60

Measure: Patient Survival

Time: Up to day 60

Description: Number residing at home or in a community setting at day 60

Measure: Number of patients residing at home or in a community setting at day 60

Time: Up to day 60

Description: Number residing at home or in a community setting at day 60, among survivors

Measure: Number of surviving patients residing at home or in a community

Time: Up to day 60
140 Characterization and Prognostic Impact of Inflammatory Responses by Host Transcriptomics and Co-infection by Metagenomics in Patients With ARDS COVID-19 in Intensive Care

Pandemic SARS-CoV-2 (COVID-19) respiratory infection is responsible for more than 4,000 deaths, mainly (67%) secondary to acute respiratory distress syndromes (ARDS). ARDS is usually associated with a mortality of around 40%, but this rate reaches 61% in patients infected with SARS-CoV-2. Two endotypes have been described in patients with ARDS: one, hyper-inflammatory, associated with very high mortality (51%); the second, slightly inflammatory (immunoparalysis), associated with much lower mortality (19%). In COVID-19 patients, distinct immune response profiles have also been observed. Some patients present deep lymphopenia and/or prolonged viral excretions associated with more frequent occurrence of co-infections (+ 29% of virus, + 23% of bacteria, + 10% of fungi). The latter group may be at higher risk in terms of mortality. The intensity of the inflammatory response and/or microbial coinfections therefore appear as risk factors for severity and mortality in patients infected with SARS-CoV-2 which determine the course of the disease. To adapt early optimal therapeutic management to each forms of the disease, it is essential to be able to characterize these profiles on the microbiological and inflammatory level. With a committed network of 6 intensive-care units across eastern and northern Ile-de-France, 180 patients with ARDS and infected with SARS-CoV-2 are being enrolled. For these patients, a nasopharyngeal swab is collected at inclusion; followed by a new nasopharyngeal swab and a deep respiratory sample once a week, until D28, for an exploration of co-infections and for monitoring the viral load of SARS-CoV-2. The rest of each of these samples are collected for the study. In parallel, the clinical data usually collected in the context of intensive care will be collected on a CRF. They will allow to calculate risk scores such as SOFA.

NCT04516486
Conditions
  1. Respiratory Distress Syndrome, Adult
  2. COVID-19
Interventions
  1. Other: retrospective metagenomics on clinical samples collected during hospitalization
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Unsupervised Transcriptomic analysis to explore the presence of 2 different groups of patients in the cohort.

Measure: Identify two endotypes (hyper-inflammatory and co-infections) and quantify their prognostic value in terms of short-term mortality (Day 28) in patients treated for ARDS infected with SARS-Cov2.

Time: Day 0 to Day 28 (longitudinal study)

Secondary Outcomes

Description: Shotgun Metagenomics analysis of respiratory samples to explore viruses, bacteria, fungi, parasites in relation with severity of the disease

Measure: Nature of viral, bacterial and fungal co-infections in the different clusters identified

Time: Day 0 to Day 28

Description: Quantification based on metagenomics through time

Measure: Comparison of SARS CoV-2 viral replication dynamics in the different clusters identified

Time: Day 0 to Day 28

Description: Viral genomic comparison and machine learning to assess the role of the mutations (quasispecies) in the severity of the disease

Measure: 4. Characterization of the viral genetic determinants selected over time in the different clusters identified

Time: Day 0 to Day 28
141 Blood Volume, Components and Capillary Leak in SARS-CoV-2 Infections

In patients with SARS-CoV-2 infection admitted to the intensive care unit (ICU), the state of the intravascular volume, the characteristics of the blood volume components, and the development of a vascular leak is currently unknown. The primary objective is to describe the blood volume, the volume of blood components, and the capillary leak and their trajectory during the early phase of hospitalization of patients with SARS-CoV-2 infection.

NCT04517695
Conditions
  1. Covid19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Device: BVA-100
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day 1

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day 2

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day 3

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day 7

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day 10

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day 14

Description: Reported by the BVA-100 software

Measure: Total blood volume (absolute and relative to ideal body weight)

Time: Day of ICU Discharge, up to day 21

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day 1

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day 2

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day 3

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day 7

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day 10

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day 14

Description: Reported by the BVA-100 software

Measure: Red blood cell volume (absolute and relative to ideal body weight)

Time: Day of ICU Discharge, up to day 21

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day 1

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day 2

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day 3

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day 7

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day 10

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day 14

Description: Reported by the BVA-100 software

Measure: Plasma volume (absolute and relative to ideal body weight)

Time: Day of ICU Discharge, up to day 21

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day 1

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day 2

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day 3

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day 7

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day 10

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day 14

Description: Reported by the BVA-100 software

Measure: Transudation rate of the 131I albumin tracer

Time: Day of ICU Discharge, up to day 21

Secondary Outcomes

Measure: Incidence of new onset renal injury (failure) and requirement for renal replacement therapy

Time: Up to Day 14
142 COVID-19 : Transcutaneous pO2 and pCO2 as Predictive Factors for Acute Respiratory Destress Syndrome in Patients Affected With SARS-Cov-2

The first case of a person infected with SARS-Cov-2 virus can be tracked back on November the 17th, 2019, in China. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 outbreak a pandemic. On April 13, COVID-19 is affecting 210 countries and territories worldwide, about 2 million positive cases have been officially declared along with 115.000 deaths. The real number of infected and deaths is scarily higher, considering that up to 65% people are asymptomatic and thus, not tested. The percentage of patients with COVID-19 needed for intensive care unit (ICU) varied from 5 to 32% in Wuhan, China. It was up to 9% in Lombardy, Italy. According to available data from Lombardy, 99% of patients admitted to the ICU needed respiratory support (88% invasive ventilation, 11% non invasive ventilation). The aim of the present investigation is to test the hypothesis whether transcutaneous partial O2 and CO2 pressures may be reliable predictive factors for acute respiratory distress syndrome (ARDS) development in hospitalized clinically stable COVID-19 positive patients and to clarify the role of the Angiotensin Converting Enzyme 2 (ACE2) and its final product, angiotensin 2 (Ang II) in the pathogenesis of this systemic disease. We also aim to test the hypothesis that plasma concentration of Clara Cell protein (CC16) and surfactant protein D (SPD), which are a biomarkers of acute lung injury, are severely decreased in COVID-19 positive patients and the plasma concentration is related to the severity of lung injury.

NCT04524156
Conditions
  1. COVID
  2. Acute Respiratory Distress Syndrome
  3. Endothelial Dysfunction
Interventions
  1. Other: Physiology
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: To test the prognostic utility of TcpO2 and TcpCO2 for the prediction of COVID19 related lung injury and acute respiratory distress syndrome (ARDS) compared to finger oxygen saturation.

Measure: Transcutaneous pO2 and pCO2 as predictive factors for respiratory deterioration

Time: 6 months

Description: To test the prognostic utility of CC16 and SPD in patients with COVID19-related acute lung injury

Measure: Pneumoproteins CC16 and SDP as predictive factors for respiratory deterioration

Time: 6 months

Description: To test the hypothesis that plasma concentration of ACE2, AngII, Ang 1-7 and Ang 1-9 are profoundly impaired in COVID-19 and may be predictive factors of clinical deterioration

Measure: Diagnostic and prognostic utility of plasma concentration of ACE2, Ang II, Ang 1-7, Ang 1-9 in COVID-19

Time: 6 months
143 Phase I/IIA Study of Descartes-30 in Acute Respiratory Distress Syndrome

Emergency study to test the safety of Descartes-30 cells in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) AND COVID-19

NCT04524962
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Covid19
Interventions
  1. Biological: Descartes 30
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

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

Measure: To assess the safety of Descartes-30 in patients with moderate-to-severe ARDS.

Time: 2 years
144 Mesenchymal Stromal Cell-based Therapy for COVID-19-associated Acute Respiratory Distress Syndrome: a Pilot Clinical Study

Considering the potential of mesenchymal stromal cells (MSCs) in the treatment of lung injuries by COVID-19, this pilot clinical trial evaluates the safety and potential efficacy of the cell therapy, administered intravenously, in patients with pneumonia associated with COVID-19-associated acute respiratory distress syndrome.

NCT04525378
Conditions
  1. Covid19
  2. ARDS, Human
Interventions
  1. Other: Mesenchymal stromal cell-based therapy
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Measure: Intrahospital mortality

Time: 28 days

Secondary Outcomes

Measure: Length of stay in the ICU and Hospital

Time: 28 days

Measure: Days without mechanical ventilation in 28 days

Time: 28 days

Measure: PaO2 / FiO2 ratio

Time: Day 1, Day 2 and Day 7 after cell infusion

Measure: Incidence of secondary infections

Time: 28 days

Measure: Incidence of adverse events

Time: 28 days

Description: Exploratory evaluation of changes from baseline (percentage) in serum levels of CRP, LDH, Ferritin levels, a panel of cytokines, chemokines immune cell populations by flow cytometry

Measure: Quantification of inflammatory response markers

Time: Day 1, Day 3 and Day 7 after cell infusion
145 A Proof of Concept Study of the Safety and Efficacy of VIB7734 for the Treatment and Prevention of Acute Lung Injury (ALI) in Patients With SARS-CoV-2 Infection

The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.

NCT04526912
Conditions
  1. Acute Lung Injury
Interventions
  1. Drug: VIB7734
  2. Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: Critical illness is defined by respiratory failure (requiring any of the following: endotracheal intubation, oxygen delivered by high flow nasal cannula, non-invasive positive pressure ventilation, extracorporeal membrane oxygenation or clinical diagnosis of respiratory failure) or shock (systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg, or requiring vasopressors)

Measure: The proportion of patients who achieve treatment success through Day 28, defined as avoidance of death and critical illness

Time: Day 1 (Baseline) through Day 28

Secondary Outcomes

Description: Defined as measure of safety

Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent fatal and life-threatening SAEs, Treatment-emergent Serious Adverse Events

Time: Day 1 (Baseline) through Day 70

Description: Safety evaluation via review of labs (white blood cell (WBC) with differential counts, hemoglobin, platelet count, liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin levels), serum chemistry, cardiac troponin coagulation markers (prothrombin time [PT], partial thromboplastin time [PTT], D dimer, fibrinogen), and urinalysis)

Measure: Change in safety laboratory parameters

Time: Day 1 (Baseline) through Day 70
146 Defibrotide Therapy for SARS-CoV2 Acute Respiratory Distress Syndrome (ARDS)

This clinical trial will enroll participants that have pneumonia caused by the COVID-19 virus. During the study patients will receive 7 to up to 14 days of defibrotide. After completing the treatment, participants will have 30 day follow-up check-up to assess for adverse events and clinical status. This final assessment can be done virtually, by telephone or electronically (email) if the patient cannot be contacted by phone. No in-person visit is required. The hypothesis of this trial is that defibrotide therapy given to patients with severe SARS-CoV2 ARDS will be safe and associated with improved overall survival, within 28 days of therapy initiation.

NCT04530604
Conditions
  1. COVID
  2. Sars-CoV2
  3. COVID-19
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Defibrotide
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale. Fatal Bleeding, and/or Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or Bleeding associated with a decline in hemoglobin level of > 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells. In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.

Measure: Number of major hemorrhagic complications within 14 days of initiation of treatment

Time: 14 days

Secondary Outcomes

Description: Proportion of the twelve patients who are alive at day 28 after starting treatment.

Measure: Overall survival

Time: 28 days

Description: Proportion of the twelve patients who are alive at Day 14 after starting treatment.

Measure: Overall survival

Time: 14 days

Description: Day 14 ventilator-free survival will be summarized by the proportion of the twelve patients who are both alive and not using a ventilator at Day 14 after starting treatment.

Measure: Ventilator free survival

Time: 14 days

Measure: Number of ventilator free days within 14 days of study entry

Time: 14 days

Description: Improvement in oxygenation defined as an increase in atio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) of 50 (or greater) compared to the nadir of PaO2/FiO2.

Measure: The time to improvement in oxygenation

Time: up to 14 days

Description: Ordinal scale: Ambulatory (1) - No limitation of activities (2) - Limitations of activities Hospitalized: (3) no oxygen therapy (4) oxygen by mask or nasal prongs Hospitalized: (5) Non-invasive ventilation or high-flow oxygen (6) Intubation and mechanical ventilation (7) Mechanical ventilation plus additional organs support-pressors, renal replacement therapy (RRT), Extracorporeal membrane oxygenation (ECMO) Dead: (8) Death

Measure: Mean change in the WHO COVID-19 Ordinal Scale during therapy

Time: up to 14 days
147 Expert Panel Statement for the Respiratory Management of COVID-19 Related Acute Respiratory Failure (C-ARF) Using Modified Delphi Methodology

The investigators aim to achieve experts consensus on respiratory interventions in management of COVID-19 related acute respiratory failure (C-ARF).

NCT04534569
Conditions
  1. Covid19
  2. Acute Respiratory Failure
  3. Acute Respiratory Distress Syndrome
Interventions
  1. Other: Experts consensus
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury

Primary Outcomes

Description: Survey Questionnaire containing seven point Likert scale and multiple choice questions.

Measure: Consensus using participating experts opinions.

Time: 20 days
148 A Pilot, Open-label, Randomised Controlled Clinical Trial to Investigate Early Efficacy of CYP-001 in Adults Admitted to Intensive Care With COVID-19

This is a pilot, multi-centre, open-label randomised controlled study to assess the early efficacy of intravenous (IV) administration of CYP-001 in adults admitted to an intensive care unit (ICU) with COVID-19.

NCT04537351
Conditions
  1. Covid19
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Biological: CYP-001
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Assessment of respiratory dysfunction

Measure: Trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups

Time: 7 days

Secondary Outcomes

Description: Assessment of safety

Measure: Incidence and severity of treatment-emergent adverse events

Time: 28 days

Description: Circulating biomarker of inflammation

Measure: Change in C-reactive protein (CRP) levels

Time: 7 days

Description: Not hospitalised, with resumption of normal activities = 1; Not hospitalised, but unable to resume normal activities = 2; Hospitalised, not requiring supplemental oxygen = 3; Hospitalised, requiring supplemental oxygen = 4; Hospitalised, requiring humidified nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both = 5; Hospitalised, requiring invasive mechanical ventilation, extracorporeal membrane oxygenation or both = 6; Death = 7

Measure: Proportional differences between groups on the Clinical Improvement Scale

Time: 28 days

Description: Assessment of respiratory dysfunction

Measure: Changes in P/F ratio

Time: 28 days

Description: Assessment of respiratory dysfunction

Measure: Changes in respiratory rate

Time: 28 days

Description: Assessment of respiratory dysfunction

Measure: Changes in oxygenation index

Time: 28 days

Description: Assessment of respiratory dysfunction

Measure: Changes in respiratory compliance (the change in lung volume per unit change in transmural pressure gradient)

Time: 28 days

Description: Assessment of respiratory dysfunction

Measure: Changes in positive end-expiratory pressure

Time: 28 days

Description: Number of days from the time of initiating unassisted breathing to D28, assuming survival for at least 48 hours after initiating unassisted breathing and continued unassisted breathing to D28

Measure: Ventilator-free days

Time: 28 days

Description: Quality of life assessment

Measure: Proportional differences between groups on the SF-36

Time: 28 days

Description: Disability assessment

Measure: Proportional differences between groups on the mini mental state examination

Time: 28 days
149 A Study of Brexanolone for Acute Respiratory Distress Syndrome Due to COVID-19

The purpose of this study is to evaluate the efficacy and safety of brexanolone in participants on ventilator support for acute respiratory distress syndrome (ARDS) due to COVID-19.

NCT04537806
Conditions
  1. Acute Respiratory Distress Syndrome
  2. COVID-19
Interventions
  1. Drug: Brexanolone
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Respiratory failure is defined based on resource utilization, requiring at least one of the following: endotracheal intubation and mechanical ventilation; oxygen delivered by high-flow nasal cannula; noninvasive positive pressure ventilation or extracorporeal membrane oxygenation (ECMO).

Measure: Percentage of Participants Who are Alive and Free of Respiratory Failure at Day 28

Time: Day 28

Secondary Outcomes

Measure: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

Time: Up to Day 28

Measure: All-cause Mortality Through Day 28

Time: Up to Day 28
150 Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status

In this study, the investigators are attempting to evaluate the influence of socio-economic factors on the functional recovery (physical and psychological) of patients who developed ARDS after a COVID-19 infection, with the aim of offering personalized medical and social follow-up and support measures in order to avoid medium- and long-term complications, which can result in handicaps, reduced quality of life, and a higher risk of death.

NCT04556513
Conditions
  1. Covid19
  2. ARDS
  3. Functional Recovery
Interventions
  1. Other: Paraclinical examination
  2. Other: Clinical Examination
  3. Other: Semi-directive interview
  4. Other: quality of life questionnaires
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Defined by the presence of at least one of the following : An alteration of the alveolar-capillary diffusion of CO <80% of the predicted normal values And/or a forced vital capacity <80% of predicted normal values and/or O2 desaturation in the 6-minute walk test And/or pulmonary parenchymatous disease with fibrosis in tomodensitometry.

Measure: Respiratory sequelae 6 months after resuscitation.

Time: Through study completion, an average of 6 months
151 Hemodynamic Impact on Critical Care Patients With Lung Damage Secondary to SARS-CoV-2 Infection

The aim of the present work is to describe the hemodynamic effects shown in patients with ARDS secondary to SARS-CoV-2 infection

NCT04556864
Conditions
  1. Covid19
  2. Hemodynamic Instability
  3. ARDS, Human
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Hypotension will be defined as a hemodynamic event that occurs when the MAP falls below 65 mmHg for a minimum duration of 1 minute (3 consecutive recordings of 1 minute or more between two consecutive falls of the MAP).

Measure: Total amount of hypotension

Time: 5 days

Secondary Outcomes

Description: We will obtain hemodynamic data for the first 5 days after the patient enters the study

Measure: Minimally invasive hemodynamic monitoring and related variables obteined from HemoSphere platform with Acumen IQ sensor (Stroke volume)

Time: 5 days

Description: We will obtain hemodynamic data for the first 5 days after the patient enters the study

Measure: Minimally invasive hemodynamic monitoring and related variables obteined from HemoSphere platform with Acumen IQ sensor (Stroke volume variation)

Time: 5 days

Description: We will obtain hemodynamic data for the first 5 days after the patient enters the study

Measure: Minimally invasive hemodynamic monitoring and related variables obteined from HemoSphere platform with Acumen IQ sensor (Cardiac index)

Time: 5 days

Description: We will obtain hemodynamic data for the first 5 days after the patient enters the study

Measure: Minimally invasive hemodynamic monitoring and related variables obteined from HemoSphere platform with Acumen IQ sensor ( HPI)

Time: 5 days

Description: We will obtain hemodynamic data for the first 5 days after the patient enters the study

Measure: Minimally invasive hemodynamic monitoring and related variables obteined from HemoSphere platform with Acumen IQ sensor (Eadyn)

Time: 5 days

Description: We will obtain hemodynamic data for the first 5 days after the patient enters the study

Measure: Minimally invasive hemodynamic monitoring and related variables obteined from HemoSphere platform with Acumen IQ sensor (dp/dt max,)

Time: 5 days

Description: start time, time of dose change, current dose

Measure: Presence of treatment with noradrenaline; presence of treatment with dobutamine, presence of treatment with other vasoactive/ionotropic/hypotensive drugs

Time: 5 days

Description: dose/24 hours

Measure: Furosemide treatment

Time: Daily during 5 days

Description: ml/24 h

Measure: Daily diuresis, daily water balance, accumulated water balance since ICU admission, daily parenteral nutrition volume, and daily enteral nutrition volume.

Time: Daily during 5 days

Description: Presence, start time and end time

Measure: Atrial fibrillation

Time: 5 days

Description: Presence and degree with KDIGO definition

Measure: Acute kidney injury

Time: Daily during 5 days

Description: Start and end date/time, dialyzing flow, replacement flow, daily balance.

Measure: Continuous renal replacement therapies

Time: 5 days

Description: Start and end date/time, blood flow.

Measure: Need for Hemadsorption

Time: 5 days

Description: Start and end date/time

Measure: Specific treatment for SARS-CoV2 (presence of tocilizumab, antimalarial drugs, antivirals)

Time: 5 days

Description: Start and end date/time

Measure: Corticoid treatment.

Time: 5 days
152 A Randomized, Double-blind, Dose-ranging, Placebo Controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (INTEGRIS-ARDS)

Evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with acute respiratory distress syndrome (ARDS) associated with at least severe COVID-19

NCT04565249
Conditions
  1. Acute Respiratory Distress Syndrome
  2. SARS-CoV-2
Interventions
  1. Drug: PLN-74809
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Number of participants with treatment-related adverse events and laboratory abnormalities, assessed by CTCAE V5.0

Time: Up to 90 days

Secondary Outcomes

Measure: Assessment of PLN-74809 plasma concentrations

Time: up to 14 days

Other Outcomes

Measure: Number of participants alive and free of invasive mechanical ventilation

Time: up to 28 days

Measure: Number of participants alive and discharged from hospital

Time: Up to 28 days

Measure: Number of participants alive and discharged from hospital

Time: Up to 90 days
153 Emergency Use Pilot Study of Cord Blood Derived Mesenchymal Stem Cells for Treatment of COVID-19 Related Acute Respiratory Distress Syndrome

This phase I trial investigates the side effects of cord blood-derived mesenchymal stem cells (MSC) in treating patients with COVID-19 infection (COVID-19)-related acute respiratory distress syndrome (ARDS). MSCs are a type of stem cell that can be taken from umbilical cord blood and grown into many different cell types that can be used to treat cancer and other diseases. The MSCs being used for infusion in this trial are collected from healthy, unrelated donors and are stored and grown in a laboratory. Giving MSC infusions may help control the symptoms of ARDS.

NCT04565665
Conditions
  1. COVID-19 Infection
  2. COVID-19-Associated Acute Respiratory Distress Syndrome
Interventions
  1. Other: Best Practice
  2. Biological: Mesenchymal Stem Cell
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Serious adverse events with be comprised of grade 3 or 4 graft versus host disease or death and will be estimated and reported overall and by group, along with 95% confidence intervals.

Measure: Incidence of composite serious adverse events (Pilot)

Time: Within 30 days of the first mesenchymal stem cell (MSC) infusion

Measure: Patients alive without grade 3, 4 infusional toxicity (Phase II)

Time: At day 30 post MSC infusion

Measure: Patients alive with grade 3 or 4 infusional toxicity (Phase II)

Time: At day 30 post MSC infusion

Measure: Patients not alive (Phase II)

Time: At day 30 post MSC infusion

Secondary Outcomes

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Proportion of successfully extubated patients who present intubated on ventilator support (Pilot)

Time: Up to day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Rate of successful progression to intubation in patients who require supplemental oxygen but who are otherwise able to breathe without assistance (Pilot)

Time: Up to day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Overall survival rate (Pilot)

Time: At day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Survival rate in patients who present intubated on ventilator support (Pilot)

Time: At day 30 post MSC infusion

Description: Will be estimated and reported with 95% confidence intervals.

Measure: Survival rate in patients who require supplemental oxygen but who are otherwise able to breathe without assistance (Pilot)

Time: At day 30 post MSC infusion

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

Measure: Determine the treatment effect on clinical parameters, oxygenation and respiratory parameters

Time: Up to day 30 post MSC infusion

Measure: Hospitalization stay (Pilot)

Time: Up to day 30 post MSC infusion

Measure: Intensive care unit stay (Pilot)

Time: Up to day 30 post MSC infusion

Description: All grades of infusion-related adverse events will be summarized by grade and type.

Measure: Incidence of infusion-related adverse events (Pilot)

Time: Up to day 30 post MSC infusion
154 Open-label Trial to Assess the Efficacy and Safety of Inhalation Use of the Approved Drug Surfactant-BL (Biosurf LLC, Russia) as a Part of Complex Therapy of Acute Respiratory Distress Syndrome (ARDS) in Patients With SARS-CoV-2 Coronavirus Infection (COVID-19)

The purpose of this study is to prove the efficacy and safety Surfactant-BL, administered by inhalation in adult hospitalized patients with ARDS due to COVID-19.

NCT04568018
Conditions
  1. ARDS Due to COVID-19
Interventions
  1. Drug: Surfactant
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Measure: Mean duration of oxygen therapy (days) in the treatment group and in the control group.

Time: within 5 days after the start of treatment

Secondary Outcomes

Measure: The proportion of patients who required ALV within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in PaO2/FiO2 ratio dynamics within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in SpO2 dynamics within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Proportion of patients who achieved an oxygenation index (PaO2/FiO2) of > 300 mm hg.

Time: within 5 days after the start of treatment

Measure: Proportion of patients dead of any reason within 30 days after the start of treatment.

Time: within 30 days after the start of treatment

Measure: Time to patient transfer to mechanically ventilated.

Time: within 30 days after the start of treatment

Measure: Change from the baseline in the severity assessment of the patient's condition according to the NEWS-II scale within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in leukocytes within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in lymphocytes within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in CRP within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in ferritin within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Measure: Change from baseline in D-dimer within 5 days after the start of treatment.

Time: within 5 days after the start of treatment

Other Outcomes

Measure: Rate of early terminations due to AE/SAE.

Time: within 30 days after the start of treatment

Measure: Proportion of patients with AEs / SAEs with highly-reliable causal relationship (certain, probable or possible) with the current WHO therapy according to the researcher's opinion.

Time: within 30 days after the start of treatment

Measure: Proportion of patients in each group with grade 3-4 AEs (CTCAE c 4.0 and higher) with highly-reliable causal relationship (certain, probable or possible) with the current WHO therapy according to the researcher's opinion.

Time: within 30 days after the start of treatment

Measure: Proportion of deaths in each group.

Time: within 30 days after the start of treatment
155 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
156 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.
157 A Novel Proportional Open Ventilation (POV) Device and Its Efficacy in Managing Acute Respiratory Failure in COVID-19 Patients

To evaluate the use of Life2000® Ventilator, a novel proportional open ventilation system in critical care use of acute onset of respiratory failure (ARF) and mild to moderate forms of acute respiratory distress syndrome (ARDS) in COVID-19 patients and its ability to provide effective ventilatory benefits and or delay patients from progressing to more aggressive forms of invasive mechanical ventilation (IMV).

NCT04581161
Conditions
  1. Acute Respiratory Failure
  2. Covid19
Interventions
  1. Device: Life2000® Ventilator
MeSH:Respiratory Insufficiency Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Compared to HFNC (AIRVO), does the Life2000® Ventilator provide clinically relevant ventilatory support to COVID-19 patients with mild to moderate ARF or ARDS to prevent IMV.

Measure: Life2000® Compared to HFNC (AIRVO)

Time: Time frame measured will include date that patient is admitted to hospital until date patient is discharged from hospital or death occurs with an anticipated 30 day time period, but shall not exceed 90 day time period.

Secondary Outcomes

Description: What level of PEEP is required to ensure adequate ventilation in COVID-19 patients with mild to moderate ARF/ARDS.

Measure: PEEP level

Time: Time frame measured will include date that patient is admitted to hospital until date patient is discharged from hospital or death occurs with an anticipated 30 day time period, but shall not exceed 90 day time period.
158 Prolonged Prone Positioning for COVID-19-induced Acute Respiratory Distress Syndrome (ARDS): A Pilot Study

Prone positioning is one of the few therapies known to improve mortality in ARDS. Traditionally, patients are proned for 16 hours per 24 hour period. Some retrospective data suggests improvement may persist beyond 16 hours. We aim to perform a pilot study comparing traditional prone positioning to prolonged prone positioning in patients with COVID-induced ARDS.

NCT04581811
Conditions
  1. ARDS
  2. Covid19
  3. Acute Hypoxemic Respiratory Failure
Interventions
  1. Other: Prolonged Proned Positioning
  2. Other: Traditional Proning Arm
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury

Primary Outcomes

Description: Time spent in the prone position

Measure: Duration in prone position

Time: 96 hours

Secondary Outcomes

Description: Change in P:F ratio from immediately prior to initiation of prone positioning to end of study period

Measure: Change in P:F ratio

Time: 96 hours

Description: Change in drive pressure from immediately prior to initiation of prone positioning to end of the study period

Measure: Change in Drive Pressure

Time: 96 hours

Description: Number of unplanned extubations

Measure: Unplanned extubations

Time: 96 hours

Description: Number of pressure ulcers

Measure: Pressure ulcers

Time: 96 hours

Description: Number of displaced central venous line or arterial line

Measure: Line displacement

Time: 96 hours

Description: Number of days on mechanical ventilation

Measure: Duration of mechanical ventilation

Time: 30 days

Description: Mortality

Measure: Mortality

Time: 30 days

Description: New initiation of inhaled pulmonary vasodilators, ECMO

Measure: Rescue Interventions

Time: 96 hours
159 A Phase 1 Study of agenT-797 to Treat Moderate to Severe Acute Respiratory Syndrome in COVID-19 Patients

A Phase 1 Study of AGENT-797 to treat moderate to severe acute respiratory syndrome in COVID-19 patients.

NCT04582201
Conditions
  1. Respiratory Distress Syndrome, Adult
Interventions
  1. Drug: agenT-797
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number and severity of adverse events (AEs)

Measure: Incidence of Treatment-Emergent Adverse Events

Time: 6 months

Description: Number of Dose Limiting Toxicities

Measure: Number of Dose Limiting Toxicities

Time: 6 months

Secondary Outcomes

Description: Time to extubation. Assessment of ventilator-free days. Oxygenation improvement as per Berlin definition (ARDS 2012). Supportive interventions used (e.g. use of prone ventilation, paralytics, pulmonary vasodilators, and other interventions affecting oxygenation).

Measure: To assess time to improvement in pulmonary function.

Time: 30 days

Description: Decay in quantitative viral burden from upper and lower respiratory tract samples collected.

Measure: Amount of virus detected in respiratory tract samples.

Time: 30 days

Description: Persistence of allogeneic invariant natural killer T cells (iNKT) non-transduced cells.

Measure: To assess longevity of agenT-797 infusion.

Time: 30 days
160 Effect of Early Corticosteroid Therapy on Mortality in Patient With Acute Respiratory Distress Syndrome Secondary to Covid-19

Study conducted on hospitalized patient in critical ill units in Nancy and Metz to evaluate if early corticosteroid treatment in first seven days after admission improve patients outcome in Acute Respiratory Distress Syndrome secondary to Covid-19 compared to later corticosteroid therapy or no treatment. Also comparison of acquired infection with or without corticosteroid treatment during hospitalisation.

NCT04586114
Conditions
  1. Acute Respiratory Distress Syndrome Secondary to Covid-19
Interventions
  1. Drug: Corticosteroids and Derivatives
MeSH:Neoplasm Metastasis Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Mortality rates in ICU in each group

Measure: Mortality in ICU

Time: within ICU stay, on average 15 days

Secondary Outcomes

Description: mortality at day 28 after ICU admission

Measure: Mortality d28

Time: 28 days

Description: cumulative incidence of infection acquired during ICU stay

Measure: acquired infections incidence

Time: 28 days

Description: number of treatment days with antibiotics during ICU stay

Measure: antibiotics duration

Time: 28 days

Description: number of days of treatment by mechanical ventilation during ICU stay

Measure: mechanical ventilation duration

Time: 28 days
161 Aerosolized Inhaled Adenosine Treatment in Patients With Acute Respiratory Distress Syndrome (ARDS) Caused by COVID-19 (The ARCTIC Trial)

This is a phase II study to test adenosine efficacy for down-regulation of the overwhelming inflammation of COVID-19 in the lungs as reflected by clinical recovery of lung function; resolution of clinically relevant markers of lung function, and resolution of systemic markers of inflammation and coagulation.

NCT04588441
Conditions
  1. Acute Respiratory Distress
Interventions
  1. Drug: Adenosine
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Improved COVID-19 symptoms measured by alive v. mortality, not hospitalized, or free of respiratory failure.

Measure: Improved COVID-19 symptoms

Time: Day 50
162 Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial

SARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease that has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of April 1, 2020, there are 874.081 numbers of confirmed cases with 43.290 fatalities. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment. Key markers implying a fatal outcome are acute respiratory distress syndrome (ARDS)-like disease with pronounced dyspnea, hypoxia and radiological changes in the lung. Senicapoc improves oxygenation and reduces fluid retention, inflammation, and bleeding in the lungs of mice with ARDS-like disease. In cells, there is an antiviral effect of senicapoc.

NCT04594668
Conditions
  1. ARDS, Human
  2. COVID
Interventions
  1. Drug: Senicapoc
MeSH:Respiratory Insufficiency Respiratory Distress Syndrome, Adult Pulmonary Valve Insufficiency
HPO:Pulmonary insufficiency

Primary Outcomes

Description: The PaO2/FiO2 ratio will be calculated based on the arterial gas closest to the time-point of Day 3 after randomization

Measure: PaO2/FiO2 ratio

Time: Day 3

Secondary Outcomes

Description: Ventilator-free days will be defined as the number of days (or proportion of days) within the first 28 days after randomization where the patient is alive and not on invasive mechanical ventilation

Measure: Ventilator-free days

Time: Day 28

Description: Assessment of mortality is considered a core outcome for trials within acute respiratory failure

Measure: Mortality

Time: Day 28

Other Outcomes

Description: An infusion of a vasopressor will be defined as any continuous infusion of noradrenaline, dopamine, dobutamine, terlipressin, vasopressin, phenylephrine, and/or adrenaline

Measure: Vasopressor-free days

Time: Day 28

Description: The Sequential Organ Failure Assessment (SOFA)-score 1-4 will be used with 1 as best and 4 as worst score. The SOFA score is a validated and widely used measure of organ failure assessing the respiratory, nervous, cardiovascular, hepatic, coagulation, and renal systems. The sub scores as well as the overall SOFA score will be assessed. The calculation of the SOFA score will be based on available clinical and laboratory data. Laboratory and clinical data closest to the given time point will be used. If a given component (e.g. bilirubin) is not available, it will be assumed to be within normal ranges.

Measure: Sequential Organ Failure Assessment (SOFA)-score

Time: Day 1, 2, 3, and 5

Description: Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration.

Measure: Need for renal replacement therapy

Time: Day 28

Description: Health-related quality of life (EQ-5D-5L) in 5 dimensions and 5 levels (1-5) with 1 as worst and 5 as best level in each dimension. At day 28 EQ-5D-5L will be assessed via telephone communication with the patient or a surrogate. The telephone interview will be semi-structured and based on the EQ-5D-5L questionnaire. The interview will be conducted by a centrally-located and trained member of the research team according to detailed standard operating procedures. In case the patient is still in the hospital, this interview will be face-to-face.

Measure: Health-related quality of life (EQ-5D-5L)

Time: Day 28

Description: Quantification of viral load before and after treatment

Measure: Measurement of SARS-CoV2 load

Time: Day 0 and 3
163 Assessment of Lung Mechanics in SARS-CoV-2/ COVID-19 Acute Respiratory Distress Syndrome: A Holistic, Longitudinal Analysis of the Lung-heart-ventilator Interaction

This study is meant to assess the lung mechanics in SARS-CoV-2 induced acute respiratory failure. A precise characterisation of lung mechanics and heart-lung-interactions might allow a better understanding of SARS-CoV-2 induced acute respiratory failure and thus lead to better mechanical ventilation strategies. This monocentric, observational study of critically ill COVID-19 patients in the ICU, will employ impedance tomography, right-heart catheterization, oesophageal pressure measurements, indirect calorimetry as well as classic mechanical ventilation parameters to characterise the mechanical characteristics of the lung as well as the heart-lung interactions in SARS-CoV-2 induced acute respiratory failure.

NCT04597853
Conditions
  1. Covid19
  2. ARDS
Interventions
  1. Diagnostic Test: Assessment of lung mechanics and heart-lung interactions
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Compliance change over the length of mechanical ventilation

Measure: Time dependent compliance change

Time: Mixed Model Assessment of compliance over time until extubation (measurements every 2 days up to 90 days)

Description: Change in Dead Space over the length of mechanical ventilation

Measure: PEEP and time dependent change in dead space

Time: Mixed Model Assessment of Dead Space over time until extubation (measurements every 2 days up to 90 days)

Description: Change in shunt fraction over the length of mechanical ventilation

Measure: PEEP and time dependent change in shunt fraction

Time: Mixed Model Assessment of shunt fraction over time until extubation (measurements every 2 days up to 90 days)
164 Survival Rates and Long-term Outcomes for Patients With COVID-19 Admitted to Norwegian ICUs

The study 'Survival rates and long-term outcomes for patients with COVID-19 admitted to Norwegian ICUs' is a national observational study, including patients admitted to a Norwegian ICU between March 2020 and March 2021. The study will describe survival rates, clinical characteristics and health challenges experienced by survivors the first year after ICU admission caused by COVID-19 disease.

NCT04601090
Conditions
  1. Covid19
  2. Acute Respiratory Failure
  3. Acute Respiratory Distress Syndrome
  4. Post Intensive Care Unit Syndrome
  5. Survivorship
Interventions
  1. Other: ICU treatment
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

Primary Outcomes

Description: Time to survival

Measure: ICU Survival rate

Time: up to 30 days

Description: Measured by self-reporting using Lawton Instrumental activity of daily living. Higher score indicates better function, and ranges from 0-8.

Measure: Change in Functional Status

Time: 6 and 12 months after ICU admission

Secondary Outcomes

Description: Measured by self-report using Hospital Anxiety and Depression Scale (HADS). Higher score indicates higher lever of anxiety and depression, scored on separate sub scales (0-21 for each).

Measure: Change in Anxiety and Depression

Time: Measured 6 and 12 months after ICU admission

Description: Measured by telephone interview using the Mini Montreal Cognitive Assessment, score ranges from 0-15. Higher score indicates better cognitive function.

Measure: Changes in Cognitive Status

Time: Measured at 6 and 12 months after ICU admission

Description: Measured by self report using (Euroqual 5 dimensions) EQ-5D. Higher score indicates worse health (range 5-15).

Measure: Change in Quality of Life 6 and 12 months after ICU admission

Time: Measured 6 and 12 months after ICU admission
165 Electrical Impedance Tomography: Collapse in Dependent Areas as a Predictor of Response to Prone Position Ventilation in COVID-19 Acute Respiratory Distress Syndrome

There are several clinical presentations of SARS-CoV-2 infection. Among the severe forms, pulmonary involvement with respiratory failure is common. Although severe lung involvement with SARS-CoV-2 meets the Berlin criteria for Acute Respiratory Distress Syndrome (ARDS), it differs from classic ARDS in that compliance (reflecting distensibility of the lung parenchyma) is frequently preserved. If the interest of Electrical Impedance Tomography has been demonstrated in classical ARDS, this is not the case in ARDS with COVID-19. However, the use of this technique in this particular patient population would make it possible to distinguish patients with severe hypoxemia linked to derecruitment from those without derecruitment, in whom hypoxemia is more likely to be linked to the loss of hypoxic vasoconstriction.

NCT04603755
Conditions
  1. SARS-CoV Infection
  2. Acute Respiratory Distress Syndrome
Interventions
  1. Device: Electrical Impedance tomography
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: The percentage of derecruitment of dependent areas will be measured every day with Electrical Impedance Tomography. The response to prone position will be assessed every day.

Measure: Coefficient of correlation between the percentage of derecruitment of dependent areas (measured with Electrical Impedance Tomography) and the response to prone position

Time: Up to 7 days
166 Impact of Intravenous Lidocaine on Clinical Outcomes of Patients With ARDS During COVID-19 Pandemia

The purpose of our prospective monocentric, randomized, controlled trial is to evaluate the effects of intravenous lidocaine on gas exchange and inflammation in acute respiratory distress syndrome (ARDS) due or not to Covid-19 pneumonia. Half of the patients will receive intravenous lidocaine and the other half will receive intravenous NaCl 0,9 % as placebo.

NCT04609865
Conditions
  1. Acute Respiratory Distress Syndrome (ARDS)
  2. COVID-19
  3. Corona Virus Infection
Interventions
  1. Drug: Lidocaine 2%
  2. Drug: Control
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: PaO2/FiO2 ratio

Measure: alveolar-capillary gas exchange after two days of treatment

Time: At 48 hours after the first treatment administration

Secondary Outcomes

Description: PaO2/FiO2 ratio : a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: alveolar-capillary gas exchange From day 0 to day 21 or until coming out of intensive care

Time: From day 0 to day 21 or until coming out of intensive care

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Ventilator-free days

Time: At day 28 and at day 90

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : Ferritin

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : bicarbonates

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : CRP

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : LDH

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : IL-6

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : Tropo HS

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : Triglycerides

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Measure the effects of Intravenous Lidocaine on Biomarkers : CBC with lymphocytes count

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Antithrombotic activity of Intravenous Lidocaine on platelets

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Antithrombotic activity of Intravenous Lidocaine on ACT ratio

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Antithrombotic activity of Intravenous Lidocaine on fibrinogen

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Antithrombotic activity of Intravenous Lidocaine on D-Dimers

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Antithrombotic activity of Intravenous Lidocaine on TEG

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Antithrombotic activity of Intravenous Lidocaine on thromboembolic events

Time: At Day 0, day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Plasma concentration of albumin and Lidocaine

Time: 4 hours after first administration, at day 2, day 7, day 14 and at day 21

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Blood pressure in mmHg will be measured

Measure: Search for hemodynamic dysfynction: Blood pressure measurement in mmHg

Time: daily from day one to day 14

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Cardiac frequency in beats per minute will be assessed

Measure: Search for hemodynamic dysfynction: Cardiac frequency in beats per minute will be assessed

Time: daily from day one to day 14

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Sinus rythm will be assessed

Measure: Search for hemodynamic dysfynction: Sinus rythm will be assessed

Time: daily from day one to day 14

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. Vasopressors and inotropes drugs use will be reported

Measure: Search for hemodynamic dysfynction: Vasopressors and inotropes drugs use will be reported

Time: daily from day one to day 14

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19. EKG : PR, QRS, QTc intervals in ms will be measured

Measure: Search for hemodynamic dysfynction: EKG : PR, QRS, QTc intervals in ms will be measured

Time: daily from day one to day 14

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: ICU ileus: laxation response

Time: daily from Day 0 to Day 28

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Opioids, sedative and curare sparing effect (drugs dosage)

Time: daily from Day 0 to Day 28

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Evaluate the impact of Lidocaine IV on ICU outcomes : re-intubation

Time: From Day0 to Day28 and at Day90

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Evaluate the impact of Lidocaine IV on ICU outcomes : ICU length of stay

Time: From Day0 to Day28 and at Day90

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Evaluate the impact of Lidocaine IV on ICU outcomes : ICU complications

Time: From Day0 to Day28 and at Day90

Description: a comparison will be made between Lidocaine and control groups in patients with acute respiratory distress syndrome (ARDS) due to Covid-19 and in patients with ARDS without Covid-19.

Measure: Cough at extubation time or in the 24 hours after extubation or weaning from respiratory support (in case of tracheostomy)

Time: extubation day
167 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
168 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
169 Post-intensive Care Follow-up of Patients Hospitalized for an Acute Respiratory Distress Syndrome (ARDS) Caused by SARS-CoV-2 (COVID-19)

For the last years, studies have described the " Post-intensive care Syndrome " (PICS), which consists in alteration of quality of life, cognition, autonomy and psychological disorders within the months after intensive-care. Patients with COVID-19 in intensive care units are at high risks to develop PICS. The primary objective is to analyse the incidence of the post-traumatic stress disorder at 12 months after intensive-care for a COVID-19 Acute Respiratory Distress Syndrome (ARDS).

NCT04619368
Conditions
  1. Human ARDS
  2. Coronavirus Infection
Interventions
  1. Other: Follow up calls
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Incidence of Post-traumatic Stress Disorder (PTSD) with the Post-traumatic Checklist-5 (PCL-5) 12 months after intensive-care

Measure: Incidence of Post-traumatic Stress Disorder (PTSD) with the Post-traumatic Checklist-5 (PCL-5) 12 months after intensive-care

Time: month 12

Secondary Outcomes

Description: psychological disorders measured by QIDS, Quick Inventory of Depressive Symptomatology. results from 0 to 27; 27 is the higher score of depressive symptoms

Measure: psychological disorders measured by QIDS

Time: Month 3

Description: psychological disorders measured by STAI-YA, State Trait Inventory Anxiety. Results from 20 to 80. 80 is the higher score of anxiety

Measure: psychological disorders measured by STAI-YA

Time: Month 3

Description: psychological disorders measured by QIDS : Quick Inventory of Depressive Symptomatology. results from 0 to 27; 27 is the higher score of depressive symptoms

Measure: psychological disorders measured by QIDS

Time: Month 6

Description: psychological disorders measured by STAI-YA, State Trait Inventory Anxiety. Results from 20 to 80. 80 is the higher score of anxiety

Measure: psychological disorders measured by STAI-YA

Time: Month 6

Description: psychological disorders measured by QIDS, Quick Inventory of Depressive Symptomatology. results from 0 to 27; 27 is the higher score of depressive symptoms

Measure: psychological disorders measured by QIDS

Time: Month 12

Description: psychological disorders measured by STAI-YA, State Trait Inventory Anxiety. Results from 20 to 80. 80 is the higher score of anxiety

Measure: psychological disorders measured by STAI-YA

Time: Month 12

Description: Quality of life measured by European Quality of Life -5 scale (overall satisfaction of Europeans concerning different aspects of life) higher score is higher quality of life

Measure: quality of life by EQL-5

Time: Month 3

Description: Quality of life measured by European Quality of Life -5 scale (overall satisfaction of Europeans concerning different aspects of life), higher score is higher quality of life

Measure: quality of life by EQL-5

Time: Month 6

Description: Quality of life measured by European Quality of Life -5 scale (overall satisfaction of Europeans concerning different aspects of life), higher score is higher quality of life

Measure: quality of life by EQL-5

Time: Month 12

Description: nutritional status measured by Nutritional Risk Screening 2002

Measure: nutritional status

Time: Month 3

Description: nutritional status measured by Nutritional Risk Screening 2002

Measure: nutritional status

Time: Month 6

Description: nutritional status measured by Nutritional Risk Screening 2002

Measure: nutritional status

Time: Month 12
170 Efficacy of Infusions of Mesenchymal Stem Cells From Wharton Jelly in the Moderate to Severe SARS-Cov-2 Related Acute Respiratory Distress Syndrome (COVID-19): A Phase IIa Double-blind Randomized Controlled Trial

Mesenchymal stem cells (MSCs) are of potential help in acute respiratory distress syndrome (ARDS), due to their anti-inflammatory properties. The investigators will analyze the effect of 3 iterative infusions of ex vivo expanded Wharton's Jelly MSCs (total dose 2.10^6/kg) in patients with ARDS due to COVID19, who require mechanical ventilation.

NCT04625738
Conditions
  1. COVID19 ARDS
Interventions
  1. Biological: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells
  2. Biological: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: The primary endpoint is the percentage of patients with a PaO2/FiO2 ratio > 200 at D10 of treatment with MSC-GW or placebo.

Measure: PaO2 / FiO2 ratio

Time: day 10

Secondary Outcomes

Description: The evolution of the PaO2/FiO2 ratio between Day 0 (or Day 1) and Day 14 of treatment with MSC-GW or placebo is a secondary endpoint.

Measure: respiratory function evolution

Time: between Day 0 (or Day 1) and Day 14 of treatment

Description: The effect of WJ-MSC on respiratory assistance is evaluated by the proportion of days without invasive respiratory assistance during the hospital stay and maximum on Day 28 (number of days without invasive respiratory assistance / number of hospital days until Day 28)

Measure: respiratory assistance

Time: between day 0 (or 1) and day 28 (or last day of hospitalization if before day 28)

Description: Difference in sequential organ failure assessment score (SOFA score), grading 0 (best) to 4 (worst), between Day 5-Day 0 and D14-Day 0

Measure: organ failures 1

Time: Day 0 to day 14

Description: number of days without extra-renal treatment treatment / number of days of hospitalization until Day 28)

Measure: organ failures 2

Time: day 0 to day 28

Description: number of days without vasopressor support

Measure: organ failures 3

Time: day 0 to day 28

Description: The duration of stay in intensive care unit

Measure: duration of intensive care

Time: day 0 to 90

Description: Cause of death during the stay in intensive care unit and during the hospital stay, on Day 28 and Day 90

Measure: Cause of death

Time: day 0 to 90

Description: respiratory morbidity on Day 90

Measure: respiratory morbidity (TDM, functional respiratory measures)

Time: day 90

Description: The evolution of the viral load is evaluated by RT PCR SARS-Cov-2 monitoring on a nasopharyngeal swab (or any other sample) at diagnosis, at Day 7, Day 14, Day 21, Day 28 or on the last day of hospitalisation

Measure: viral load

Time: day 0 to day 28 (or last day of hospitalization if before day 28)

Description: - The anti-HLA antibody rate measured on Day 0 (before initiating treatment), on Day 28 and on Day 90

Measure: Anti-HLA antibody rate

Time: day 0 to day 90

Description: The occurrence of immediate hypersensitivity reactions (chills, hyperthermia associated with hypotension) within 4 to 6 hours of the WJ MSC or placebo infusion.

Measure: immediate hypersensitivity reactions

Time: day 0, day 3, day 5 (+/- 1day)

Description: The thromboembolic risks monitored biologically by routinely daily monitoring of hemostasis (TP, TCA, Fibrinogen, D-dimers)

Measure: thromboembolic adverse events 1

Time: day 0 to day 14

Description: daily monitoring of transthoracic echocardiography

Measure: thromboembolic adverse events 2

Time: day 0 to day 14

Description: blood cultures in case of T° > 38,5°C

Measure: infectious adverse events

Time: day 0 to day 14
171 A Phase 1 Double-blinded, Randomized, Placebo-controlled Study for COVID-19 and Influenza Virus-Elicited Acute Respiratory Distress Syndrome (ARDS) Using Longeveron Mesenchymal Stem Cells (LMSCs)

A Phase I, double- blinded, randomized, placebo- controlled study to test the safety of LMSCs in Adults suffering from mild to severe acute respiratory distress syndrome (ARDS) due to COVID-19 resultant from 2019-nCoV coronavirus infection, or resultant from influenza virus infection.

NCT04629105
Conditions
  1. ARDS, Human
  2. Covid19
Interventions
  1. Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
  2. Other: Placebo
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Incidence of treatment-emergent serious adverse events (TE-SAEs) within 4 weeks after treatment, defined as one or more of the following untoward medical occurrences happening within the first 4 weeks after treatment. i. Life-threatening event (e.g., stroke or non-fatal pulmonary embolism). ii. Event requiring inpatient hospitalization or prolongation of existing hospitalization (e.g., for worsening dyspnea). iii. Event resulting in persistent or significant disability/incapacity. iv. Event resulting in death. v. Event leading to other clinically significant untoward laboratory test result(s) or medical condition(s), as determined by the Investigator.

Measure: Incidence of Treatment-Emergent Serious Adverse Events

Time: Within 4 weeks after treatment

Description: Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.

Measure: Number of Participants with Abnormal Clinical Significant Laboratory Values in Hematology.

Time: Baseline to 6 Months

Description: Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 months, this change in overall assessment will be the outcome in numbers of particants with a change.

Measure: Number of Participants with Changes in Echocardiography Overall Assessment

Time: Baseline to 6 Months

Description: Number of Participants with changes to Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 Months

Measure: Number of Participants with Changes to overall assessment of Electrocardiogram

Time: Baseline to 6 Months

Description: Time to recovery of Sp02 to 90% or higher on room air (or the oxygen concentration the patient had before acute illness) after 10 minutes of spontaneous breathing.

Measure: Time to recovery of Sp02

Time: Baseline to 6 Months

Description: Number of Participants with Abnormal Clinical Significant Lab Values in Blood Chemistry testing will be assessed at Baseline and 6 Months.

Measure: Number of Participants with Abnormal Clinical Significant Lab Values in the Blood Chemistry testing.

Time: Baseline to 6 months

Description: Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation testing will be assessed at Baseline and 6 Months.

Measure: Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation.

Time: Baseline to 6 months

Description: Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.

Measure: Number of Participants with Abnormal Clinical Significant Lab Values in the Urinalysis

Time: Baseline to 6 months

Secondary Outcomes

Description: Geometric mean titer

Measure: Immunity

Time: Baseline to 6 Months

Description: Change in overall assessment via Lung imaging via chest X-ray will be assessed and compared between baseline and 6 months

Measure: Change in Imaging via X-ray

Time: Baseline to 6 Months

Description: Change in overall assessment via Lung imaging via computerized tomography will be assessed and compared between baseline and 6 months

Measure: Change in Imaging via Computerized Tomography

Time: Baseline to 6 Months
172 The TRISTARDS Trial - ThRombolysIS Therapy for ARDS A Phase IIb/III Operationally Seamless, Open-label, Randomised, Sequential, Parallel-group Adaptive Study to Evaluate the Efficacy and Safety of Daily Intravenous Alteplase Treatment Given up to 5 Days on Top of Standard of Care (SOC) Compared With SOC Alone, in Patients With Acute Respiratory Distress Syndrome (ARDS) Triggered by COVID-19

This is a study in adults with severe breathing problems because of COVID-19. People who are in hospital on breathing support can participate in the study. The purpose of the study is to find out whether a medicine called alteplase helps people get better faster. The study has 2 parts. In the first part, participants are put into 3 groups by chance. Participants in 2 of the groups get 2 different doses of alteplase, in addition to standard treatment. Participants in the third group get standard treatment. In the second part of the study, participants are put into 2 groups by chance. One group gets alteplase and standard treatment. The other group gets only standard treatment. Alteplase is given as an infusion into a vein. In both study parts, treatments are given for 5 days. Doctors monitor patients and check whether their breathing problems improve. They compare results between the groups after 1 month. Participants are in the study for 3 months.

NCT04640194
Conditions
  1. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: Alteplase
  2. Procedure: Standard of care
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Time from randomisation to either an improvement of two points on the 11-point WHO Clinical Progression Scale or discharge from the hospital, whichever comes first. The WHO Clinical Progression Scale ranges from 0 to 10. A higher score indicates a worsening of the patient status.

Measure: Time to clinical improvement or hospital discharge

Time: Up to day 28

Secondary Outcomes

Measure: All cause mortality

Time: At day 28

Measure: Number of ventilator-free days

Time: From start of treatment to day 28

Description: The SOFA score ranges from 0 to 6. A higher score indicates a worsening of the symptoms.

Measure: Improvement of Sequential (sepsis-related) Organ Failure Assessment (SOFA) score by ≥2 points

Time: From baseline to end of day 6

Description: according to International Society on Thrombosis and Haemostasis (ISTH) definition

Measure: Number of major bleeding events (MBE)

Time: Up to day 6

Description: PaO2: partial oxygen pressure in arterial blood FiO2: fraction of inspired oxygen SpO2: Oxygen saturation

Measure: Daily average PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change

Time: From baseline to end of day 6

Measure: All-cause mortality or on mechanical ventilation

Time: At day 28
173 Expanded Access to ZofinTM (OrganicellTM Flow) for the Treatment of Patients With Mild to Moderate COVID-19 Due to SARS-Cov-2 for Outpatient and Inpatient Population

This expanded access protocol will provide access to the investigational product ZofinTM (OrganicellTM Flow) for patients in outpatient facilities infected with SARS-CoV-2 who have mild to moderate COVID-19, or who are judged by a healthcare provider to be at high risk of progression to moderate disease.

NCT04657406
Conditions
  1. Covid19
  2. Corona Virus Infection
  3. SARS (Severe Acute Respiratory Syndrome)
  4. Acute Respiratory Distress Syndrome
Interventions
  1. Drug: ZofinTM (OrganicellTM Flow)
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

174 A Randomized, Double Blind, Multicenter, Placebo Controlled, Parallel Group, Exploratory Efficacy and Safety Study of Glenzocimab in SARS-Cov-2-related Acute Respiratory Distress Syndrome

A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study to evaluate the efficacy and safety of glenzocimab in ARDS.

NCT04659109
Conditions
  1. SARS-CoV Infection
  2. Acute Respiratory Distress Syndrome
  3. COVID-19
  4. ARDS
Interventions
  1. Drug: glenzocimab
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acu Acute Lung Injury Syndrome

Primary Outcomes

Description: Progression from moderate to severe assessed at Day 4 is a composite failure endpoint defined as the occurrence of at least one of the following failure events : Respiratory rate (RR) ≥ 30/min, or Oxygen Saturation (SpO2) ≤ 93% in resting state, or Oxygen Pressure/ Inspired fraction (PaO2/FiO2) ≤ 200mmHg Death occurring prior to or on Day 4

Measure: Progression from moderate to severe respiratory distress assessed at Day 4

Time: Day 4

Secondary Outcomes

Measure: All cause mortality at day 40

Time: Day 40 (maximum)

Description: WHO COVID-19 Ordinal Scoring Scale is 9 point ordinal scale

Measure: WHO-COVID-19 Scale

Time: Up to Day 40

Description: Determines the degree of illness of a patient and prompts critical care intervention (recommended by NHS over original NEWS): total possible score ranges from 0 to 20. The higher the scores the greater the clinical risk.

Measure: NEWS-2 Scale

Time: Up to Day 40

Description: Respiratory Rate status defined as:: o Normal:<20/min, Mild:20/min≤RR<24/min, Moderate:24/min≤RR<30/min, o Severe:≥30/min, Death.

Measure: Respiratory Rate status (RR)

Time: Up to Day 40

Description: Hypoxemia status defined as:: o Normal:>300mmHg, Mild: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg, Moderate:100mmHg Measure: Hypoxemia status

Time: Up to Day 40

Description: SpO2 status defined as: o Normal:>95% Mild:93% Measure: SpO2 status

Time: Up to Day 40

Measure: CHEST CT-Scan (or in exceptional cases, chest radiogram)

Time: Day 4

Measure: Oxygen-free days

Time: Up to Day 40

Measure: Admission to the ICU

Time: Up to Day 40

Measure: ICU-free days

Time: Up to Day 40

Measure: Hospital-free days

Time: Up to Day 40

Measure: Clinical recovery and Time to Clinical recovery

Time: Up to Day 40

Measure: Cure and Time-to-cure

Time: Up to Day 40

Measure: Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)

Time: Up to Day 40

Measure: Incidence of bleeding-related events

Time: Up to Day 40

Measure: Incidence of hypersensitivity reactions

Time: Up to Day 40

Measure: Changes from baseline on blood pressure

Time: Up to Day 40

Measure: Changes from baseline on heart rate

Time: Up to Day 40

Measure: Changes from baseline on NFS

Time: Up to Day 40

Measure: Changes from baseline on INR/PTT

Time: Up to Day 40

Measure: Changes from baseline on platelet count

Time: Up to Day 40

Measure: Changes from baseline on plasma fibrinogen level

Time: Up to Day 40

Measure: Changes from baseline on plasma D-Dimers level

Time: Up to Day 40

Measure: Changes from baseline on serum-glucose level

Time: Up to Day 40

Measure: Changes from baseline on urea level

Time: Up to Day 40

Measure: Changes from baseline on creatinemia

Time: Up to Day 40

Measure: Changes from baseline on LFTs (ASAT/ALAT)

Time: Up to Day 40

Measure: Changes from baseline on CRP level

Time: Up to Day 40

Measure: Changes from baseline on LDH level

Time: Up to Day 40

Measure: Changes from baseline on IL6 level

Time: Up to Day 40

Measure: Changes from baseline on Tnt

Time: Up to Day 40

Measure: Changes from baseline on NT proBNP

Time: Up to Day 40

Measure: Changes from baseline on procalcitonin level

Time: Up to Day 40

Measure: Changes from baseline on ferritin level

Time: Up to Day 40

Description: Changes in one or several of the usual ECG parameters compared to baseline or screening, i.e. sinusal rhythm, cardiac axis, QRS value, QT/QTc segment, Wave direction, and any abnormality.

Measure: ECG over the course of the study versus screening

Time: Up to Day 40
175 Remote Ischemic Conditioning as an Adjunct Therapy for Severe COVID-19 Disease: a Prospective Randomized Pilot Study

This research aims to assess the use of an experimental and non-invasive procedure, Remote Ischemic Conditioning (RIC), as an adjunct therapy in attenuating severe COVID-19 disease. An excessive and counterproductive systemic inflammatory response is thought to be a major cause of severe disease and death in patients with COVID-19. Severe ICU cases frequently have markedly higher levels of inflammatory markers such as CRP, IL-6, IL and TNF-a; which is thought to be correlated with increasing disease severity. The relationship between dysregulated inflammatory processes and disease states such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are well understood. ALI is characterized by an acute exaggerated mononuclear/neutrophilic inflammatory response followed by progressive collagen deposition in the lung, and if severe enough, may progress to ARDS requiring ventilation.

NCT04659460
Conditions
  1. COVID
  2. Corona Virus Infection
  3. Acute Lung Injury
  4. Ischemia Limb
  5. Acute Respiratory Distress Syndrome
Interventions
  1. Device: Remote Ischemic Conditioning
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

Primary Outcomes

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Interleukin 1-Beta (IL-1B) (pg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Interleukin 6 (IL-6) (pg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

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

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Tumour Necrosis Factor Alpha (TNFa) (pg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Neutrophil to Lymphocyte Ratio (NLR) (absolute neutrophils/lymphocytes)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Serum Ferritin (ng/mL)

Time: Through study completion - up to 12 months

Description: Standard coagulation parameter, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: International Normalized Ratio (INR)

Time: Through study completion - up to 12 months

Description: Standard coagulation parameter, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Prothrombin Time (PTT)

Time: Through study completion - up to 12 months

Description: ROTEM coagulation assessment using the commercial ROTEM device traditionally used for the assessment of coagulopathy, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point).

Measure: Rotational Thromboelastometry (ROTEM)

Time: Through study completion - up to 12 months

Secondary Outcomes

Description: Number of continuous calendar days or partial calendar days including treatment with invasive ventilation.

Measure: Total duration of mechanical ventilation (number of days)

Time: Through study completion - up to 12 months

Description: Number of continuous calendar days or partial calendar days admitted to an acute care hospital.

Measure: Intensive Care Unit Length of Stay (number of days)

Time: Through study completion - up to 12 months

Description: Number of continuous calendar days or partial calendar days admitted to an acute care hospital.

Measure: Hospital Length of Stay (number of days)

Time: Through study completion - up to 12 months
176 Controlled Trial of Fenofibrate for Patients With COVID-19 Requiring Hospitalization

This is an open-label run-in followed by a randomized, double-blind drug treatment study of COVID-19 infected patients requiring inpatient hospital admission.

NCT04661930
Conditions
  1. Corona Virus Disease (COVID-19)
  2. Respiratory Distress Syndrome
  3. SARS-CoV-2 Infection
Interventions
  1. Drug: TriCor® 145mg tablets
  2. Other: Usual Care
  3. Other: Placebo
MeSH:Virus Diseases Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Blood will be collected every third day for the duration of study participation. D-dimer Neutrophils Lymphocytes Platelets (PLT) Glucose Lactate C-Reactive Protein (CRP) Cardiac Troponin (TRO) Ferritin

Measure: Difference in Plasma markers at 14 days

Time: 14 days

Description: Outcome reported as the number of participants who have expired at 14 days post enrollment.

Measure: 14-Day Mortality

Time: 14 days

Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available.

Measure: Difference in Estimated P/F Ratio at 14 days

Time: 14 days

Description: Nasopharyngeal swabs will be collected every fourth day for the duration of study participation. as number of viral genetic copies per mL.

Measure: Viral Clearance by Nasopharyngeal Swab

Time: 14 days

Secondary Outcomes

Description: Outcome reported as the mean number of days participants in each arm had 2 or more abnormal plasma levels of: D-dimer Neutrophils Lymphocytes Platelets (PLT) Glucose Lactate C-Reactive Protein (CRP) Cardiac Troponin (TRO) Ferritin

Measure: Number of Abnormal Biomarker Days

Time: 14 days

Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio) and Expiratory Pressure.

Measure: Difference in Estimated PEEP adjusted P/F Ratio at 14 days

Time: 14 days

Description: PaO2 or SaO2 and FiO2. Partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry. FiO₂ is estimated from oxygen flow/delivery rates

Measure: Difference in Oxygenation at 14 days

Time: 14 days

Description: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL, new treatment with pressures, increase in 50% pressure or fluid rate) per participant in each arm.

Measure: Daily Hypotensive Episodes

Time: 14 days

Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

Measure: Hypotension Requiring Vasopressors

Time: 14 days

Description: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.

Measure: Acute Kidney Injury

Time: 14 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). Total score is calculated by entering patient data into a SOFA calculator, a widely available software. Total scores range from 0-24, with higher scores indicating greater risk of mortality.

Measure: Sequential Organ Failure Assessment (SOFA) Total Score

Time: 14 days

Description: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.

Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S)

Time: 14 days

Description: Outcome reported as the number of participants who have expired at 28 days post enrollment.

Measure: 28-Day Mortality

Time: 28 days

Description: Outcome reported as the number of participants who have expired at 90 days post enrollment.

Measure: 90-Day Mortality

Time: 90 days

Description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

Measure: ICU Admission

Time: 14 days

Description: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

Measure: Number of Ventilator-Free Days

Time: 14 days

Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

Measure: Number of Therapeutic Oxygen-Free Days

Time: 14 days

Description: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

Measure: Number of Vasopressor-Free Days

Time: 14 days

Description: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.

Measure: Length of ICU Stay

Time: 14 days

Description: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

Measure: Length of Hospital Stay

Time: 14 days

Description: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.

Measure: Incidence of Respiratory Failure

Time: 14 days

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

Measure: Change in PROMIS Dyspnea Functional Limitations

Time: 14 days

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

Measure: Change in PROMIS Dyspnea Severity

Time: 14 days

Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. 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: Disease Severity Rating

Time: 14 days

Description: Nasopharyngeal swabs will be collected every fourth day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Nasopharyngeal Swab

Time: 14 days

Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

Measure: Viral Load by Blood

Time: 14 days

Description: Blood will be collected every third day for viral load assessment for the duration of study participation. clearance is measured as fold change in viral genetic copies per mL.

Measure: Viral Clearance by Blood

Time: 14 days
177 Wide Scale Monitoring for Acute Respiratory Infection Using a Mobile-Based Study Platform

This is a prospective observational study using a mobile study platform (app) that is designed for use on Android phones. Study participants will provide baseline demographic and medical information and report symptoms of respiratory infection on a weekly basis using the app. Participants will also report use of prevention techniques on the weekly survey. Mobility data will be collected passively using the sensors on the participant's smartphone, if the participant has granted the proper device permissions. The overall goals of the study are to track spread of coronavirus-like illness (CLI), influenza-like illness (ILI) and non-specific respiratory illness (NSRI) on a near-real time basis and identify specific behaviors associated with an increased or decreased risk of developing these conditions.

NCT04663776
Conditions
  1. Covid19
  2. Influenza
  3. Respiratory Tract Infections
  4. Acute Respiratory Tract Infection
  5. Acute Respiratory Distress Syndrome
MeSH:Infection Communicable Diseases Respiratory Tract Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
HPO:Respiratory tract infection

Primary Outcomes

Description: The definition of ILI will be adapted from CDC guidelines as a participant reporting fever in addition to cough or sore throat without any other known cause. All study analyses and outcomes will be reported using federated analytics. Federated analytics utilizes aggregated responses, rather than individual subject reports. Due to this, when reporting the final outcome, the total incidence may not add up to exactly 100%.

Measure: Incidence of influenza-like illness (ILI) and COVID-like illness (CLI) in a study participant.

Time: 6-month participation period

Description: CLI will be defined as fever and cough, or shortness of breath, or loss of smell. Incidence will be defined as reporting of the above symptoms in the 7 days prior (and not previously). All study analyses and outcomes will be reported using federated analytics. Federated analytics utilizes aggregated responses, rather than individual subject reports. Due to this, when reporting the final outcome, the total incidence may not add up to exactly 100%.

Measure: Incidence of COVID-like illness (CLI) in a study participant.

Time: 6-month participation period

Secondary Outcomes

Description: Patterns of mobility (e.g. time away from home, use of public transportation), and reported use of prevention strategies such as wearing a mask and social distancing in participants who do, or don't, develop CIL and/or ILI will be compared. All study analyses and outcomes will be reported using federated analytics. Federated analytics utilizes aggregated responses, rather than individual subject reports. Due to this, when reporting the final outcome, the total prevalence may not add up to exactly 100%.

Measure: Disease Prevalence

Time: 1-year study period
178 Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome to Prevent Tracheal Intubation: the COVID-NIV Study

Non-invasive ventilation can allow to avoid intubation and improve outcomes in moderate-to-severe COVID-19-associated acute respiratory distress-syndrome (ARDS). Data on NIV parameters adjustment based on expanded respiratory and gas exchange monitoring in COVID-19 associated ARDS is limited. Appropriate adjustment of the inspiratory positive airway pressure (IPAP) set as a point of the balance between minimal work of breathing (minimum point of W.Patrick scale for assessment of the accessory respiratory muscles and minimum diaphragm thickening fraction) and minimum tidal volume, and respiratory rate can decrease NIV failure in moderate-to-severe COVID-ARDS. The objective of the study is to evaluate the ability of non-invasive ventilation guided with expanded respiratory monitoring to decrease the intubation rate in in moderate-to-severe COVID-ARDS.

NCT04667923
Conditions
  1. Covid19
  2. ARDS
Interventions
  1. Diagnostic Test: Respiratory monitoring
  2. Diagnostic Test: Respiratory muscles ultrasound
  3. Diagnostic Test: Electro impedance tomography
  4. Diagnostic Test: Capnography
  5. Diagnostic Test: Arterial blood gas
  6. Diagnostic Test: Quasistatic pressure-volume curve
MeSH:Respiratory Distress Syndrome, Newborn Respi Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Frequency of NIV failure

Measure: Intubation rate

Time: On day 28

Description: Mortality on day 28

Measure: Mortality

Time: On day 28

Secondary Outcomes

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: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation

Description: Measurement of arterial carbon dioxide tension, minute ventilation and calculation of ventilatory ratio

Measure: Change in ventilatory ratio

Time: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation

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: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation

Description: Measurement of exhaled tidal volume

Measure: Change in tidal volume

Time: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation

Description: Calculation of the Patrick's scale (minimum 0 points, maximum 5 points, more points means worse outcome)

Measure: Change in accessory respiratory muscles workload

Time: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
179 Pathological Findings in Critically-ill Patients Who Died From SARS-CoV-2 Related Acute Respiratory Distress Syndrome

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new coronavirus discovered in December 2019 in Wuhan, China and currently responsible of a worldwide outbreak and the death of more than 55,000 patients in France. The more severe form of COVID-19 disease induces a pneumonia with profound hypoxemia which may require invasive mechanical ventilation. It is estimated that 5% of COVID-19 patients are admitted to the Intensive Care Unit (ICU) for management. Hospital mortality in patients who develop severe acute respiratory distress syndrome (ARDS) ranges between 40% and 60%. The investigators purpose to investigate the pathological findings of COVID-19 patients who died from ARDS in the ICU by doing post-mortem lung biopsies

NCT04675281
Conditions
  1. SARS-CoV-2
  2. Covid19
  3. Pathology
  4. Intensive Care Units
  5. Respiratory Distress Syndrome
Interventions
  1. Other: 2 post-mortem transcutaneous lung biopsies (1 anterior ; 1 posterior) using anatomical landmarks
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Syndrome

Primary Outcomes

Description: Detailed description and analysis of the primary lesions of the lungs in patients who died in the ICU from Covid-19.

Measure: Analysis of the pathological findings of a large cohort of patients who died from COVID-19 in the ICU

Time: Two post-mortem lung biopsies performed immediately after death.

Secondary Outcomes

Description: Comparison of pathological findings according to the time between ICU admission and death.

Measure: Comparison between early (<1 week after ICU admission) and late (≥1 week) deaths

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Comparison of pathological findings according to the length of acute respiratory syndrome.

Measure: Analysis of the influence of ARDS severity and length on pathological findings

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Comparison of pathological findings according to the duration of acute respiratory syndrome.

Measure: Analysis of the influence of ARDS severity and length on pathological findings

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Comparison of pathological findings between patients who received steroids and those who did not.

Measure: Analysis of the influence of pharmacological treatments (steroids) on pathological findings

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Comparison between radiological description of the CT of the lungs and the radiological findings.

Measure: Analysis of the correlation between radiological findings and pathological findings

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Analysis of the pathological findings according to the primary cause of death (hypoxia, shock, hypoxia and shock, cardiac arrest, other).

Measure: Association between the primary cause of death and pathological findings

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Analysis of the correlation between the ventilator settings (tidal volume, PEEP, driving pressure, plateau pressure, static compliance, volume or pressure mode) and pathological findings.

Measure: Analysis of the correlation between the ventilator settings and pathological findings

Time: Two post-mortem lung biopsies performed immediately after death.

Description: Description of the co-infection (bacterial or fungal infections) documented by pathological findings

Measure: Co-infections

Time: Two post-mortem lung biopsies performed immediately after death.
180 Short-term Effects of Prone Positioning on Tissue Oxygen Saturation, Measured by Near-infrared Spectroscopy, in COVID-19 Patients With Acute Respiratory Distress Syndrome

The purpose of this study is to monitor short-term changes in tissue oxygen saturation and local blood flow as results of changing from supine to prone position in ARDS COVID-19 patients

NCT04692129
Conditions
  1. Covid19
  2. ARDS, Human
MeSH:Respiratory Distress Syndrome, Adult

Primary Outcomes

Measure: Change in tissue oxygenation (StO2)

Time: 20 minutes

Measure: Change in local hemoglobin content

Time: 20 minutes

Secondary Outcomes

Measure: Compare changes in tissue oxygenation and arterial oxygenation

Time: 20 minutes

HPO Nodes


HPO

Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


HPO Nodes


Reports

Data processed on January 01, 2021.

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

Google Colab

Python example via Google Colab Notebook