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  • HP:0002090: Pneumonia
  • Pneumonia (312) Abnormality of the cardiovascular system (29) Neoplasm (27) Respiratory tract infection (27) Hypoxemia (22) Depressivity (21) Diabetes mellitus (19) Acute kidney injury (19) Abnormal lung morphology (19) Thromboembolism (17) Hypertension (16) Anosmia (14) Myocardial infarction (14) Abnormality of coagulation (14) Stroke (13) Pulmonary embolism (13) Arthritis (12) Leukemia (12) Interstitial pneumonitis (12) Autistic behavior (11) Mental deterioration (11) Deep venous thrombosis (10) Type II diabetes mellitus (10) Pulmonary obstruction (10) Crohn's disease (10) Abnormality of the kidney (9) Autism (9) Obesity (9) Congestive heart failure (9) Chronic pulmonary obstruction (9) Chronic pain (9) Rheumatoid arthritis (8) Abnormality of the liver (8) Respiratory distress (8) Pulmonary fibrosis (8) Colitis (8) Myocarditis (8) Carcinoma (8) Ulcerative colitis (8) Behavioral abnormality (7) Dementia (7) Infertility (7) Inflammation of the large intestine (7) Pulmonary insufficiency (7) Low levels of vitamin D (7) Neoplasm of the lung (7) Type I diabetes mellitus (7) Psychosis (6) Coronary artery atherosclerosis (6) Lymphoma (6) Abnormality of the gastrointestinal tract (6) Chronic kidney disease (6) Sepsis (6) Renal insufficiency (5) Lymphopenia (5) Gastroparesis (5) Immunodeficiency (5) Systemic lupus erythematosus (5) Breast carcinoma (5) Peripheral arterial stenosis (5) Allergy (5) Encephalopathy (4) Hepatic fibrosis (4) Cardiac arrest (4) Dysphagia (4) Asthma (4) Alzheimer disease (4) Osteoarthritis (4) Neoplasm of the pancreas (4) Autoimmunity (4) Disseminated intravascular coagulation (4) Attention deficit hyperactivity disorder (4) Sleep apnea (4) Prostate cancer (4) Neoplasm of head and neck (4) Addictive behavior (4) Insomnia (4) Obsessive-compulsive behavior (3) Seizure (3) Cardiomyopathy (3) Weight loss (3) Fever (3) Migraine (3) Pulmonary arterial hypertension (3) Bronchiectasis (3) Obstructive sleep apnea (3) Colon cancer (3) Reduced factor VIII activity (3) Malnutrition (3) Knee osteoarthritis (3) Lymphoid leukemia (3) Renal cell carcinoma (3) Arrhythmia (3) Fatigue (3) Endometriosis (3) Non-small cell lung carcinoma (3) Neuroendocrine neoplasm (3) Hypercoagulability (3) Schizophrenia (3) Hearing impairment (2) Visual impairment (2) Conjunctivitis (2) Uveitis (2) Agoraphobia (2) Abnormality of the endocrine system (2) Abnormal heart morphology (2) Tachycardia (2) Angina pectoris (2) Gastroesophageal reflux (2) Neurodegeneration (2) Abnormal intestine morphology (2) Alopecia of scalp (2) Mutism (2) Headache (2) Transient ischemic attack (2) Hyperkinetic movements (2) Polyphagia (2) Atherosclerosis (2) Hypoventilation (2) Myelodysplasia (2) Psoriasiform dermatitis (2) Paroxysmal atrial fibrillation (2) Acute myeloid leukemia (2) Lymphoproliferative disorder (2) Myeloproliferative disorder (2) Multiple myeloma (2) Intervertebral disc degeneration (2) Stridor (2) Cystoid macular edema (2) Hemeralopia (2) Cutaneous melanoma (2) Arteritis (2) Glioblastoma multiforme (2) Cervix cancer (2) Pulmonary edema (2) Ovarian neoplasm (2) Angioedema (2) Mania (2) Neoplasm of the large intestine (2) Urinary retention (1) Urinary incontinence (1) Nephritis (1) Menorrhagia (1) Xerostomia (1) Hypogeusia (1) Conductive hearing impairment (1) Abnormality of the eye (1) Cataract (1) Amblyopia (1) Periodontitis (1) Enuresis (1) Hypoparathyroidism (1) Adrenal insufficiency (1) Hyperaldosteronism (1) Osteopenia (1) Abnormality of the skin (1) Jaundice (1) Lymphedema (1) Angiokeratoma corporis diffusum (1) Keratoconjunctivitis (1) Spasticity (1) Hemiparesis (1) Polyneuropathy (1) Syncope (1) Meningitis (1) Cerebral hemorrhage (1) Abnormal joint morphology (1) Hepatic steatosis (1) Hepatic failure (1) Hepatocellular carcinoma (1) Premature birth (1) Sudden cardiac death (1) Aortic valve stenosis (1) Bradycardia (1) Torsade de pointes (1) Atrioventricular block (1) Pancreatitis (1) Abnormality of blood and blood-forming tissues (1) Gout (1) Diarrhea (1) Anorexia (1) Esophageal varix (1) Hypothermia (1) Apnea (1) Status epilepticus (1) Subarachnoid hemorrhage (1) Memory impairment (1) Difficulty walking (1) Encephalitis (1) Waddling gait (1) Increased intracranial pressure (1) Celiac disease (1) Biliary cirrhosis (1) Hypotension (1) Osteomyelitis (1) Squamous cell carcinoma (1) Central apnea (1) Hypokalemia (1) Hyponatremia (1) Hyperphosphatemia (1) Skeletal muscle atrophy (1) Male infertility (1) Spondylolisthesis (1) Myalgia (1) Back pain (1) Low back pain (1) Muscular dystrophy (1) Neonatal death (1) Thrombophlebitis (1) Chronic bronchitis (1) Ventricular tachycardia (1) Coronary artery stenosis (1) Chronic lymphatic leukemia (1) Hypersensitivity pneumonitis (1) Intraalveolar phospholipid accumulation (1) Abnormal anterior horn cell morphology (1) Amyotrophic lateral sclerosis (1) Neoplasm of the skin (1) Female infertility (1) Benign prostatic hyperplasia (1) Hip osteoarthritis (1) Stomatitis (1) Uterine neoplasm (1) Intestinal atresia (1) Inflammatory abnormality of the skin (1) Sinus tachycardia (1) Bronchiolitis (1) Postprandial hyperglycemia (1) Hepatitis (1) Erythroid hypoplasia (1) Hodgkin lymphoma (1) B-cell lymphoma (1) Myeloid leukemia (1) Chronic myelomonocytic leukemia (1) Morphea (1) Bronchitis (1) Hypercapnia (1) Pain (1) Retinal vein occlusion (1) Vasovagal syncope (1) Neonatal asphyxia (1) Dyspareunia (1) Heart murmur (1) Cardiogenic shock (1) Cholangitis (1) Cholangiocarcinoma (1) Small cell lung carcinoma (1) Vulvar neoplasm (1) Neonatal sepsis (1) Glue ear (1) Subdural hemorrhage (1) Endocarditis (1) Toxemia of pregnancy (1) Myositis (1) Vaginal neoplasm (1) Cellulitis (1) Self-injurious behavior (1) Bulimia (1) Neoplasm of the rectum (1) Chest pain (1) Atelectasis (1) Lymphocytosis (1) Polymenorrhea (1)

    HP:0002090: Pneumonia

    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 (527)


    Name (Synonyms) Correlation
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    drug2037 Methylprednisolone Wiki 0.12
    drug3485 Tocilizumab Wiki 0.11
    Name (Synonyms) Correlation
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    drug2337 Opaganib Wiki 0.08
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    drug4171 vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki 0.08
    drug1895 Low molecular weight heparin Wiki 0.08
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    drug1033 Dexamethasone injection Wiki 0.08
    drug3496 Tofacitinib Wiki 0.08
    drug2186 Niclosamide Oral Tablet Wiki 0.08
    drug1879 Low Dose Radiation Therapy Wiki 0.08
    drug3142 SivoMixx (200 billion) Wiki 0.08
    drug444 Baricitinib Oral Tablet Wiki 0.08
    drug473 Bevacizumab Injection Wiki 0.08
    drug4023 oxygen therapy Wiki 0.08
    drug1913 Lung ultrasound Wiki 0.08
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    drug2632 Prednisone Wiki 0.07
    drug2572 Placebos Wiki 0.07
    drug1465 Heparin Wiki 0.07
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    drug1520 Hydroxychloroquine Wiki 0.06
    drug2878 Respiratory mechanics measurement Wiki 0.06
    drug3916 iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki 0.06
    drug3563 UCMSCs Wiki 0.06
    drug2491 Physical Therapy Wiki 0.06
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    drug4179 γ-Globulin Wiki 0.06
    drug3821 canakinumab Wiki 0.06
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    drug74 ACT-20-MSC Wiki 0.06
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    drug598 CHEST CT SCAN Wiki 0.06
    drug2141 NP-120 (Ifenprodil) Wiki 0.06
    drug3254 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki 0.06
    drug1790 LB1148 Wiki 0.06
    drug2367 Ozanimod Wiki 0.06
    drug3964 mesenchymal stem cells Wiki 0.06
    drug3732 XAV-19 Wiki 0.06
    drug1493 Home Sleep Apnea Testing or In-hospital Polysomnography Wiki 0.06
    drug2096 Moxifloxacin or Levofloxacin Wiki 0.06
    drug3269 Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki 0.06
    drug149 Abidol Hydrochloride combined with Interferon atomization Wiki 0.06
    drug593 CERC-002 Wiki 0.06
    drug1307 Favipiravir tablets Wiki 0.06
    drug3613 VC Wiki 0.06
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    drug1719 Intranasal heparin sodium (porcine) Wiki 0.06
    drug3567 UTTR1147A Wiki 0.06
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    drug850 Combined use of a respiratory broad panel multiplex PCR and procalcitonin Wiki 0.06
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    drug3256 Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki 0.06
    drug2887 Retrospective case-control analysis Wiki 0.06
    drug1100 Drug: NA-831 - 0.10 mg/kg Wiki 0.06
    drug3273 Sterile Water for Injection Wiki 0.06
    drug2410 PT-Pal Wiki 0.06
    drug2132 NK Cells Wiki 0.06
    drug1188 Endoscopic intervention Wiki 0.06
    drug1021 Dental pulp mesenchymal stem cells Wiki 0.06
    drug907 Convalescent anti-SARS-CoV-2 plasma Wiki 0.06
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    drug440 Bariatric procedures Wiki 0.06
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    drug1501 Hormones Wiki 0.06
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    Correlated MeSH Terms (71)


    Name (Synonyms) Correlation
    D011014 Pneumonia NIH 0.96
    D011024 Pneumonia, Viral NIH 0.43
    D018352 Coronavirus Infections NIH 0.16
    Name (Synonyms) Correlation
    D045169 Severe Acute Respiratory Syndrome NIH 0.16
    D053717 Pneumonia, Ventilator-Associated NIH 0.16
    D017563 Lung Diseases, Interstitial NIH 0.15
    D007249 Inflammation NIH 0.09
    D012128 Respiratory Distress Syndrome, Adult NIH 0.08
    D011020 Pneumonia, Pneumocystis NIH 0.08
    D000077299 Healthcare-Associated Pneumonia NIH 0.08
    D013577 Syndrome NIH 0.08
    D008171 Lung Diseases, NIH 0.07
    D055371 Acute Lung Injury NIH 0.07
    D012127 Respiratory Distress Syndrome, Newborn NIH 0.06
    D000542 Alveolitis, Extrinsic Allergic NIH 0.06
    D001049 Apnea NIH 0.06
    D001261 Pulmonary Atelectasis NIH 0.06
    D001469 Barotrauma NIH 0.06
    D004617 Embolism NIH 0.06
    D018410 Pneumonia, Bacterial NIH 0.06
    D016769 Embolism and Thrombosis NIH 0.06
    D001768 Blister NIH 0.06
    D055370 Lung Injury NIH 0.05
    D012140 Respiratory Tract Diseases NIH 0.05
    D013927 Thrombosis NIH 0.05
    D003141 Communicable Diseases NIH 0.05
    D000860 Hypoxia NIH 0.05
    D007239 Infection NIH 0.05
    D012120 Respiration Disorders NIH 0.04
    D011665 Pulmonary Valve Insufficiency NIH 0.04
    D012141 Respiratory Tract Infections NIH 0.04
    D009767 Obesity, Morbid NIH 0.04
    D030341 Nidovirales Infections NIH 0.04
    D000075902 Clinical Deterioration NIH 0.04
    D003967 Diarrhea NIH 0.04
    D009410 Nerve Degeneration NIH 0.04
    D004646 Emphysema NIH 0.04
    D007040 Hypoventilation NIH 0.04
    D011251 Pregnancy Complications, Infectious NIH 0.03
    D020181 Sleep Apnea, Obstructive NIH 0.03
    D001987 Bronchiectasis NIH 0.03
    D053120 Respiratory Aspiration NIH 0.03
    D011654 Pulmonary Edema NIH 0.03
    D008173 Lung Diseases, Obstructive NIH 0.03
    D014777 Virus Diseases NIH 0.03
    D020141 Hemostatic Disorders NIH 0.03
    D013923 Thromboembolism NIH 0.03
    D001778 Blood Coagulation Disorders NIH 0.03
    D011655 Pulmonary Embolism NIH 0.03
    D012891 Sleep Apnea, NIH 0.03
    D060085 Coinfection NIH 0.03
    D003693 Delirium NIH 0.03
    D009102 Multiple Organ Failure NIH 0.03
    D006967 Hypersensitivity, NIH 0.03
    D003333 Coronaviridae Infections NIH 0.03
    D007154 Immune System Diseases NIH 0.02
    D012327 RNA Virus Infections NIH 0.02
    D016638 Critical Illness NIH 0.02
    D013313 Stress Disorders, Post-Traumatic NIH 0.02
    D009765 Obesity NIH 0.02
    D011248 Pregnancy Complications NIH 0.02
    D004417 Dyspnea NIH 0.02
    D006333 Heart Failure NIH 0.02
    D005355 Fibrosis NIH 0.02
    D012598 Scoliosi NIH 0.02
    D009103 Multiple Sclerosis NIH 0.02
    D007251 Influenza, Human NIH 0.01
    D002318 Cardiovascular Diseases NIH 0.01
    D040921 Stress Disorders, Traumatic NIH 0.01
    D014947 Wounds and Injuries NIH 0.01
    D009369 Neoplasms, NIH 0.01

    Correlated HPO Terms (25)


    Name (Synonyms) Correlation
    HP:0006515 Interstitial pneumonitis HPO 0.15
    HP:0002088 Abnormal lung morphology HPO 0.08
    HP:0002104 Apnea HPO 0.06
    Name (Synonyms) Correlation
    HP:0006516 Hypersensitivity pneumonitis HPO 0.06
    HP:0002014 Diarrhea HPO 0.06
    HP:0100750 Atelectasis HPO 0.06
    HP:0001907 Thromboembolism HPO 0.05
    HP:0012418 Hypoxemia HPO 0.05
    HP:0011947 Respiratory tract infection HPO 0.04
    HP:0010444 Pulmonary insufficiency HPO 0.04
    HP:0002791 Hypoventilation HPO 0.04
    HP:0100598 Pulmonary edema HPO 0.04
    HP:0002180 Neurodegeneration HPO 0.04
    HP:0006536 Pulmonary obstruction HPO 0.04
    HP:0002870 Obstructive sleep apnea HPO 0.03
    HP:0002110 Bronchiectasis HPO 0.03
    HP:0002204 Pulmonary embolism HPO 0.03
    HP:0001928 Abnormality of coagulation HPO 0.03
    HP:0010535 Sleep apnea HPO 0.03
    HP:0012393 Allergy HPO 0.03
    HP:0002098 Respiratory distress HPO 0.02
    HP:0001635 Congestive heart failure HPO 0.02
    HP:0001513 Obesity HPO 0.02
    HP:0002664 Neoplasm HPO 0.01
    HP:0001626 Abnormality of the cardiovascular system HPO 0.01

    Clinical Trials

    Navigate: Correlations   HPO

    There are 312 clinical trials


    1 Antibiotic Treatment Trial Directed Against Chlamydia Pneumonia in Multiple Sclerosis

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease which affects the central nervous system (CNS). The etiology of MS is unknown, although the immune system appears to play a role. Many different infectious agents have been proposed as potential causes for MS, including Epstein-Barr virus, human herpesvirus 6, and coronaviruses. Recently Dr. Sriram at Vanderbilt University has found evidence for active Chlamydia pneumonia infection in the CNS of MS patients. These findings have been replicated in part by other laboratories. The purpose of the current study is to test whether antibiotic treatment aimed at eradicating Chlamydia infection will reduce the disease activity in MS. The primary outcome measure will be reduction in new enhancing MS lesions on brain MRI. Forty patients will be entered into the trial. To be eligible, patients must have evidence of chlamydia infection in their spinal fluid and enhancing lesions on their pre-randomization MRI scans. Patients who meet these criteria will be randomized to either placebo or antibiotic therapy, and followed for 6 months on treatment.

    NCT00043264
    Conditions
    1. Multiple Sclerosis
    Interventions
    1. Drug: Rifampin
    2. Drug: Azithromycin
    MeSH:Pneumonia Multiple Sclerosis Sclerosis
    HPO:Pneumonia

    2 The Impact of Simultaneous Presence of Viral and Bacterial Pathogens on Therapy and Course of Severe Pneumonia

    The purpose of the study is to determine if the clinical course of pneumonia is more severe when both, bacterial and viral pathogens are find as possible causative agent and how does it affect treatment.

    NCT02203110
    Conditions
    1. Community Acquired Pneumonia
    2. Hospital Acquired Pneumonia
    3. Ventilator Associated Pneumonia
    MeSH:Pneumonia, Ventilator-Associated Healthcare-Associated Pneumonia Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Rate of changes in empirical antibiotic therapy due to broad microbiological diagnostic

    Time: each patient will be assessed at enrollment and follow-up for 2 months
    3 The Place of Imaging and Microbiology in the Diagnosis of Pneumonia in the Elderly: PneumOldCT

    Diagnosis of pneumonia in the elderly is difficult because of the poor sensitivity and specificity of clinical signs as well as images from chest radiography (RT). New diagnostic tools such as thoracic low-dose computed tomography (CT), which exposes the patient to a weak dose of irradiation, could improve diagnosis. Moreover, low-dose CT could provide additional accuracy in the etiological clarification of pneumonia in elderly people. As a first step, the investigators aim to perform a 1 year (12 months of inclusion + 3 months of follow-up) prospective study including the Divisions of Internal Medicine, Rehabilitation, Geriatrics and Radiology of the University Hospitals of Geneva. In this study, patients >65 years old with a clinical suspicion of low respiratory tract infection (LRTI) will be included. They will be prescribed antimicrobial therapy. Both chest radiography and low-dose thoracic CT will be performed within the first 72 hours after admission, as will blood tests and a nasopharyngeal swab. The clinician's diagnosis, both before and after the results of the CT, will be compared at the end of the study to the adjudication committee's diagnostic opinion which will have access to all available clinical, laboratory and chest X-ray data and which will be considered the gold standard. At the end of the study, all the CT images will be blind-reviewed by two experts in radiology. The impact of CT scanning in the diagnosis of pneumonia will be assessed, both for its sensitivity and specificity in this population. During the first 12 months of the study, all patients will undergo a systematic nasopharyngeal swab at admission and at discharge, from which eluates will be conserved. During the next 12 months, virological and bacteriological polymerase chain reactions (PCR) will be performed, using new diagnostic tools, in order to determine the etiological diagnosis in this population and to evaluate the impact of the new tools in the management of pneumonia for this population. Analysis of these data will allow clinical, radiological and microbiological correlation.

    NCT02467192
    Conditions
    1. Pneumonia
    Interventions
    1. Device: Low dose CT
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of upgraded or downgraded diagnoses

    Time: During the 24 hours after CT

    Secondary Outcomes

    Measure: Number of bacterial and viral pulmonary infections

    Time: During hospitalisation (maximum 3 months)
    4 Effects of Low-dose Corticosteroids on Survival of Severe Community-acquired Pneumonia

    Mortality of severe Community-Acquired Pneumonia (CAP) has not declined over time and is between 25 and 30% in sub-groups of patients. Corticosteroids (CTx) could down-regulate pulmonary and systemic inflammation, accelerate clinical resolution and decrease the rate of inflammation-associated systemic complications. Two recent meta-analyses suggest a positive effect on severe CAP day 28 survival when CTx are added to standard therapy. However they are based on only four trials gathering less than 300 patients, of which only one was positive. Recently published guidelines do not recommend CTx as part of CAP treatment. Therefore a well-powered trial appears necessary to test the hypothesis that CTx - and more specifically hydrocortisone - could improve day 28 survival of critically-ill patients with severe CAP, severity being assessed either on a Pulmonary Severity Index ≥ 130 (Fine class V) or by the use of mechanical ventilation or high-FiO2 high-flow oxygen therapy. A phase-III multicenter add-on randomized controlled double-blind superiority trial assessing the efficacy of hydrocortisone vs. placebo on Day 28 all-causes mortality, in addition to antibiotics and supportive care, including the correction of hypoxemia. Randomization will be stratified on: (i) centers; (ii) use of mechanical ventilation at the time of inclusion.

    NCT02517489
    Conditions
    1. Community Acquired Pneumonia
    Interventions
    1. Drug: Hydrocortisone
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Day 28 all causes mortality

    Time: at day 28

    Description: For the sub-group of patients included with COVID19, failure is defined as death or need of respiratory support (mechanical ventilation or high-flow oxygen therapy);

    Measure: Day 21 failure

    Time: at day 21

    Secondary Outcomes

    Measure: In patients non-invasively ventilated at inclusion, proportion of patients needing endotracheal intubation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: In patients non-ventilated at inclusion, proportion of patients requiring non-invasive ventilation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: In patients non-ventilated at inclusion, proportion of patients needing endotracheal intubation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Day 28 ventilator-free-days

    Time: between 0 and day 28

    Measure: Number of patients with vasopressor therapy initiation from inclusion to day 28

    Time: between 0 and day 28

    Measure: Day 28 vasopressor-free-days

    Time: between 0 and day 28

    Measure: ICU and/or intermediate care unit LOS

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: All-causes mortality at day 90

    Time: at day 90

    Measure: SF-36 Health Survey at day 90

    Time: at day 90

    Measure: Biomarkers: procalcitonin at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: Biomarkers: C-reactive protein at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: Biomarkers: plasmatic concentration of pro-inflammatory cytokines (IL-6, IL-20, IL-22, IL-22BP, HBD2, TNF) at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: P/F ratio measured daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28

    Time: measured daily from baseline to day 7, at the end of treatment i.e 14 days after the start of treatment, at the end of ICU-stay (for a maximum of 28 days) and/or day 28

    Measure: SOFA calculated daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28

    Time: calculated daily from baseline to day 7, at the end of treatment (i.e 14 days after the start of treatment), at the end of ICU-stay (for a maximum of 28 days) and/or day 28

    Measure: Proportion of patients experiencing secondary infection during their ICU-stay

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Proportion of patients experiencing gastrointestinal bleeding during their ICU-stay

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Daily amount of insulin administered to the patient from day 1 to day 7

    Time: Patients will be followed from day 1 to day 7

    Measure: Weight-gain at baseline and day 7

    Time: Patients will be followed at baseline and day 7

    Other Outcomes

    Description: Sub-group of patients included with COVID19

    Measure: P/F ratio measured daily from Day1 to Day7, at Day 14 and at Day 21 and/or at the end of ICU-stay

    Time: from day 1 to day 7, at day 14 and day 21 and/or at the end of ICU-stay

    Description: Sub-group of patients included with COVID19

    Measure: Proportion of patients needing endotracheal intubation

    Time: at day 21

    Description: Sub-group of patients included with COVID19

    Measure: Proportion of patients experiencing secondary infection during their ICU-stay

    Time: From baseline to day 21
    5 Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia

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

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

    Primary Outcomes

    Measure: All-cause mortality

    Time: Day 90

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

    Measure: Days alive and not receiving organ support in ICU

    Time: Day 21

    Secondary Outcomes

    Measure: ICU Mortality

    Time: Day 90

    Measure: ICU length of stay

    Time: Day 90

    Measure: Hospital length of stay

    Time: Day 90

    Measure: Ventilator free days

    Time: Day 28

    Measure: Organ failure free days

    Time: Day 28

    Measure: All-cause mortality

    Time: 6 months

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

    Measure: Health-related Quality of life assessment

    Time: 6 months

    Measure: Proportion of intubated patients who receive a tracheostomy

    Time: Day 28

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

    Measure: Destination at time of hospital discharge

    Time: Free text Day 90

    Measure: Readmission to the index ICU during the index hospitalization

    Time: Day 90

    Measure: World Health Organisation 8-point ordinal scale outcome

    Time: Hospital discharge

    Other Outcomes

    Description: Antibiotic Domain specific outcome

    Measure: Occurrence of multi-resistant organism colonisation/infection

    Time: Day 90, censored at hospital discharge

    Description: Antibiotic Domain specific outcome

    Measure: Occurrence clostridium difficile

    Time: Day 90, censored at hospital discharge

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

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

    Time: Day 90, censored at hospital discharge

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

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

    Time: Day 3, up to Day 7

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

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

    Time: Day 90, censored at hospital discharge
    6 Trial of Respiratory Infections in Children for Enhanced Diagnostics

    The overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical community acquired pneumonia. Specific objectives: - To assess the diagnostic accuracy of MxA for viral CAP (sub-study I) - To study etiologies in children with CAP (sub-study II) - To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III) - To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV) - To assess long-term complications in children with CAP (sub-study V The study takes place at Sachs' Children and Youth hospital in Stockholm.

    NCT03233516
    Conditions
    1. Community-acquired Pneumonia
    MeSH:Respiratory Tract Infections Pneumonia
    HPO:Pneumonia Respiratory tract infection

    Primary Outcomes

    Description: Clinically relevant difference in MxA-levels between cases with viral and bacterial clinical CAP

    Measure: MxA - cases with viral and bacterial clinical CAP

    Time: 2021

    Description: Clinically relevant difference in MxA-levels between cases with viral clinical CAP and controls

    Measure: Mxa viral clinical CAP and controls

    Time: 2021

    Description: Proportion of respiratory pathogens in cases and controls, using real time PCR

    Measure: PCR - respiratory pathogens in cases and controls

    Time: 2020

    Description: Sensitivity and specificity for different respiratory viruses with MariPOC® Respi as compared to real-time PCR

    Measure: Sensitivity and specificity - MariPOC

    Time: 2021

    Description: Sensitivity and specificity for different respiratory viruses with a novel PCR-based point-of-care test as compared to PCR

    Measure: Sensitivity and specificity a novel PCR-based point-of-care test

    Time: 2021

    Description: Difference in asthma prevalence between cases and controls and difference in number of hospital-requiring respiratory infections between cases and controls after 3, 7 and 10 years

    Measure: Difference asthma prevalence and number of hospital-requiring respiratory infections - cases and controls,

    Time: 2027

    Secondary Outcomes

    Description: Clinically relevant difference in MxA-levels comparing cases with viral clinical CAP with cases with atypical and mixed viral-bacterial clinical CAP as well as with controls with and without presence of respiratory viruses by PCR

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Clinically relevant differences in MxA-levels in cases with regard to specific respiratory agents

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Sensitivity and specificity for MxA in identifying viral clinical CAP

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Sensitivity and specificity for identifying viral and bacterial infection respectively for CRP, PCT and combination test of CRP, PCT and MxA

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Difference in CRP and PCT between children with viral, bacterial, atypical bacterial and mixed viral-bacterial infection

    Measure: Assessment of PCT and CRP as clinical biomarkers

    Time: 2021

    Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases with viral, bacterial, atypical bacterial and mixed viral-bacterial infection

    Measure: Descriptive statistics of study cohort with regard to etiologic agent

    Time: 2020

    Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases who tested positive for respiratory virus by MariPOC® Respi as compared to those with a negative test

    Measure: Evaluation of MariPOC® Respi in a clinical setting

    Time: 2022

    Description: Number of hospital-requiring respiratory infections in cases and controls

    Measure: Assessment of long-term outcomes of children with CAP

    Time: 2027

    Description: Difference in asthma prevalence between cases with viral and bacterial clinical CAP as compared to an estimate of the prevalence in the general population

    Measure: Assessment of long-term outcomes of children with CAP

    Time: 2027

    Description: Difference in proportion of hospital-requiring respiratory infections between cases with viral, bacterial, atypical and mixed viral-bacterial infection

    Measure: Assessment of long-term outcomes of children with CAP

    Time: 2027

    Description: Difference in MxA-levels between PCR+/MariPOC® Respi+ and PCR+/MariPOC® Respi- study subjects.

    Measure: Evaluation of MariPOC® Respi

    Time: 2022

    Description: Estimation of etiology of cases using two levels of certainty (definitive as well as probable definition).

    Measure: Etiology of cases in TREND study

    Time: 2020
    7 SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia

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

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

    Primary Outcomes

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

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

    Time: Within 30 days of enrollment in study.

    Secondary Outcomes

    Description: Death from any cause

    Measure: Mortality

    Time: Within 30 days and 90 days of study enrollment

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

    Measure: Progression of disease

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

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

    Measure: Evolution of respiratory failure

    Time: Within 72 hours of enrollment in study.

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

    Measure: Evolution of kidney failure

    Time: Within 72 hours of enrollment in study.

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

    Measure: Evolution of shock

    Time: Within 72 hours of enrollment in study.

    Description: In hospital and in ICU

    Measure: Length of stay

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

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

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

    Time: Up to day +5 following study enrollment.

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

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

    Time: Up to day +5 following study enrollment.

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

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

    Time: Up to day +14 following study enrollment.
    8 ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA)

    This research study seeks to establish the effectiveness of a combination of an inhaled corticosteroid and a beta agonist compared to placebo for the prevention of acute respiratory failure (ARF) in hospitalized patients with pneumonia and hypoxemia.

    NCT04193878
    Conditions
    1. Pneumonia
    2. Hypoxemia
    3. Acute Respiratory Failure
    Interventions
    1. Drug: Inhaled budesonide and formoterol
    2. Drug: Inhaled placebo
    MeSH:Pneumonia Respiratory Insufficiency Hypoxia
    HPO:Hypoxemia Pneumonia

    Primary Outcomes

    Description: High flow nasal cannula (HFNC) and/or Noninvasive ventilation (NIV) use for greater than 36 hours OR Invasive mechanical ventilation for greater than 36 hours OR Death in a patient placed on respiratory support (HFNC, NIV, ventilator) who dies before 36 hours

    Measure: Acute respiratory failure (ARF)

    Time: within 7 days of randomization

    Secondary Outcomes

    Measure: Hospital length of stay

    Time: within 60 days of randomization

    Measure: Duration of need for supplemental oxygen

    Time: within 60 days of randomization

    Measure: Proportion of patients intubated for respiratory failure

    Time: Within 7 days of randomization
    9 Effects of Traditional Chinese Medicines (TCMs) on Patients With COVID-19 Infection: A Perspective, Open-labeled, Randomized, Controlled Trial

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

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

    Primary Outcomes

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

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

    Time: 14 days

    Secondary Outcomes

    Description: Time to complete remission of fever in eligible subjects

    Measure: The time to fever resolution rate

    Time: 14 days

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

    Measure: Time to recovery of lung injury

    Time: 14 days

    Other Outcomes

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

    Measure: Rate of subjects who die

    Time: 28 days

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

    Measure: Rate of subjects receiving systematic corticosteroids

    Time: 28 days

    Description: The length of hospital stays

    Measure: The length of hospital stays

    Time: 28 days

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

    Measure: The duration of respiratory support

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

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

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

    Primary Outcomes

    Description: Evaluation of Pneumonia Improvement

    Measure: Size of lesion area by chest radiograph or CT

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

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

    Measure: Side effects in the MSCs treatment group

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

    Secondary Outcomes

    Description: Evaluation of Pneumonia Improvement

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

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

    Description: Marker for COVID-19

    Measure: Time of nucleic acid turning negative

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

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: Day 28

    Description: Marker of Immunological function

    Measure: CD4+ and CD8+ T celll count

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

    Description: Markers of organ function

    Measure: Alanine aminotransferase

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

    Description: Markers of Infection

    Measure: C-reactive protein

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

    Description: Markers of organ function

    Measure: Creatine kinase

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

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

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

    Primary Outcomes

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

    Time: 7 days after randomization

    Secondary Outcomes

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

    Time: 3 days after randomization

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

    Time: 5 days after randomization

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

    Time: 14 days after randomization

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

    Measure: The critical illness rate of subjects at weeks 2

    Time: 14 days after randomization

    Measure: The mortality rate of subjects at weeks 2

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

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

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

    Primary Outcomes

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

    Measure: Rate of disease remission

    Time: two weeks

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

    Measure: Time for lung recovery

    Time: two weeks

    Secondary Outcomes

    Measure: Rate of no fever

    Time: two weeks

    Measure: Rate of respiratory symptom remission

    Time: two weeks

    Measure: Rate of lung imaging recovery

    Time: two weeks

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

    Time: two weeks

    Measure: Rate of undetectable viral RNA

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

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

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

    Primary Outcomes

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

    Measure: Rate of disease remission

    Time: two weeks

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

    Measure: Time for lung recovery

    Time: two weeks

    Secondary Outcomes

    Measure: Rate of no fever

    Time: two weeks

    Measure: Rate of respiratory symptom remission

    Time: two weeks

    Measure: Rate of lung imaging recovery

    Time: two weeks

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

    Time: two weeks

    Measure: Rate of undetectable viral RNA

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

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

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

    Primary Outcomes

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

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

    Time: 2 weeks

    Secondary Outcomes

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

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

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

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

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

    Primary Outcomes

    Measure: Virus negative conversion rate in the first week

    Time: first week

    Secondary Outcomes

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

    Measure: Virus negative conversion rate

    Time: 14-20 days

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

    Measure: Antipyretic rate

    Time: 14-20 days

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

    Measure: Symptom relief time

    Time: 14-20 days

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

    Measure: Finger oxygen improvement rate

    Time: 14-20 days

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

    Measure: Disease progression rate

    Time: 14-20 days

    Measure: Mortality rate

    Time: 14-20 days

    Measure: Incidence of severe adverse reactions

    Time: 14-20 days

    Measure: Change curve of peripheral blood lymphocyte count

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

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

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

    Primary Outcomes

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

    Measure: Rate of comprehensive adverse outcome

    Time: 14 days

    Secondary Outcomes

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

    Measure: Time of clinical remission

    Time: 28 days

    Measure: Rate of no fever

    Time: 14 days

    Measure: Rate of no cough

    Time: 14 days

    Measure: Rate of no dyspnea

    Time: 14 days

    Measure: Rate of no need for oxygen inhalation

    Time: 14 days

    Measure: Rate of undetectable viral RNA

    Time: 14 days

    Measure: Rate of mechanical ventilation

    Time: 28 days

    Measure: Rate of ICU admission

    Time: 28 days

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

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

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

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

    Primary Outcomes

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

    Measure: Clinical improvement based on the 7-point scale

    Time: 28 days after randomization

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

    Measure: Lower Murray lung injury score

    Time: 7 days after randomization

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

    Measure: Lower Murray lung injury score

    Time: 14 days after randomization

    Secondary Outcomes

    Description: Number of deaths during study follow-up

    Measure: 28-day mortality

    Time: Measured from Day 0 through Day 28

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

    Measure: Duration of mechanical ventilation

    Time: Measured from Day 0 through Day 28

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

    Measure: Duration of hospitalization

    Time: Measured from Day 0 through Day 28

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

    Measure: Proportion of patients with negative RT-PCR results

    Time: 7 and 14 days after randomization

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

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

    Time: 7,14 and 28 days after randomization

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

    Measure: Proportion of patients with normalized inflammation factors

    Time: 7 and 14 days after randomization

    Description: Frequency of Adverse Drug Events

    Measure: Frequency of Adverse Drug Events

    Time: Measured from Day 0 through Day 28

    Description: Frequency of Serious Adverse Drug Events

    Measure: Frequency of Serious Adverse Drug Events

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

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

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

    Primary Outcomes

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

    Time: 3 days after randomization

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

    Time: 5 days after randomization

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

    Time: 7 days after randomization

    Measure: The mortality rate of subjects at weeks 2

    Time: 14 days after randomization

    Secondary Outcomes

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

    Time: 14 days after randomization

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

    Measure: The critical illness rate of subjects at weeks 2

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

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

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

    Primary Outcomes

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

    Measure: Rate of disease remission

    Time: day 7

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

    Measure: Rate and time of entering the critical stage

    Time: day 7

    Secondary Outcomes

    Description: Rate of patients without fever at day 7

    Measure: Rate of normal tempreture

    Time: day 7

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

    Measure: Rate of respiratory symptom remission

    Time: day 7

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

    Measure: Rate of lung imaging recovery

    Time: day 7

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

    Measure: Rate of laboratory indicator recovery

    Time: day 7

    Description: Rate of patients withundetectable viral RNA at day 7

    Measure: Rate of undetectable viral RNA

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

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

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

    Primary Outcomes

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

    Measure: Ventilation-free days

    Time: on the day 28 after enrollment

    Secondary Outcomes

    Description: wether the patient survives

    Measure: 28-days mortality

    Time: on the day 28 after enrollment

    Description: days of the patients staying in the ICU

    Measure: ICU length of stay

    Time: on the day 28 after enrollment

    Description: the rate of CPR

    Measure: Demand for first aid measuments

    Time: on the day 28 after enrollment

    Description: days of using vasopressors

    Measure: Vasopressor days

    Time: on the day 28 after enrollment

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

    Measure: Respiratory indexes

    Time: on the day 10 and 28 after enrollment

    Description: Ecmo or ventilator

    Measure: Ventilator parameters

    Time: on the day 10 and 28 after enrollment

    Description: Acute Physiology and Chronic Health Evaluation

    Measure: APACHE II scores

    Time: on the day 10 after enrollment

    Description: Sepsis-related Organ Failure Assessment

    Measure: SOFA scores

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

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

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

    Primary Outcomes

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

    Measure: Time to Clinical Improvement (TTCI)

    Time: up to 28 days

    Secondary Outcomes

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

    Measure: Clinical status assessed by the ordinal scale

    Time: up to 28 days

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

    Measure: The differences in oxygen intake methods

    Time: up to 28 days

    Measure: Duration (days) of supplemental oxygenation

    Time: up to 28 days

    Measure: Duration (days) of mechanical ventilation

    Time: up to 28 days

    Measure: The mean PaO2/FiO2

    Time: up to 28 days

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

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

    Time: up to 28 days

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

    Time: up to 28 days

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

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

    Time: up to 28 days

    Measure: Length of hospital stay (days)

    Time: up to 28 days

    Measure: All cause mortality

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

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

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

    Primary Outcomes

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

    Measure: Oxygenation index

    Time: on the day 14 after enrollment

    Secondary Outcomes

    Description: whether the patient survives

    Measure: 28 day mortality

    Time: on the day 28 after enrollment

    Description: days of the patients in hospital

    Measure: Hospital stay

    Time: up to 6 months

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

    Measure: 2019-nCoV antibody test

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

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

    Measure: 2019-nCoV nucleic acid test

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

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

    Measure: Improvement of lung imaging examinations

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

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

    Measure: White blood cell count

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

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

    Measure: Lymphocyte count

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

    Description: procalcitonin in microgram(ug)/L

    Measure: Procalcitonin

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

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

    Measure: interleukin(IL)-2

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

    Description: IL-4 in pg/mL

    Measure: IL-4

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

    Description: IL-6 in pg/mL

    Measure: IL-6

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

    Description: IL-10 in pg/mL

    Measure: IL-10

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

    Description: TNF-α in nanogram(ng)/L

    Measure: tumor necrosis factor(TNF)-α

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

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

    Measure: γ-interferon(IFN)

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

    Description: CRP in microgram(μg)/L

    Measure: C-reactive protein(CRP)

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

    Description: counts of CD4+ T-Lymphocytopenia in litre

    Measure: CD4+ T-Lymphocytopenia

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

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

    Measure: CD8+ T-Lymphocytopenia

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

    Description: counts of NK in a litre

    Measure: natural killer cell(NK)

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

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

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

    Primary Outcomes

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

    Measure: the incidence of treatment failure in 14 days

    Time: 14 days

    Secondary Outcomes

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

    Measure: clinical cure incidence in 14 days

    Time: 14 days

    Description: the duration from admission to virus negative

    Measure: the duration of virus change to negative

    Time: 30 days

    Description: the patient die in 30 days

    Measure: mortality at day 30

    Time: 30 days

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

    Measure: ICU admission rate in 30 days

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

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

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

    Primary Outcomes

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

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

    Time: up to 28 days

    Secondary Outcomes

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

    Measure: All cause mortality

    Time: up to 28 days

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

    Measure: Frequency of respiratory progression

    Time: up to 28 days

    Description: in those with fever at enrolment

    Measure: Time to defervescence

    Time: up to 28 days

    Other Outcomes

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

    Measure: Time to cough reported as mild or absent

    Time: up to 28 days

    Description: patients with moderate / severe dyspnea when enrolled

    Measure: Respiratory improvement time

    Time: up to 28 days

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

    Time: up to 28 days

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

    Time: up to 28 days

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

    Time: up to 28 days

    Measure: Frequency of requirement for mechanical ventilation

    Time: up to 28 days

    Measure: Frequency of serious adverse events

    Time: up to 28 days

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

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

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

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

    Primary Outcomes

    Description: Evaluation of Pneumonia Improvement

    Measure: Pneumonia severity index

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

    Description: Evaluation of Pneumonia Improvement

    Measure: Oxygenation index (PaO2/FiO2)

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

    Secondary Outcomes

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

    Measure: Side effects in the UC-MSCs treatment group

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

    Description: Marker for efficacy of treatment

    Measure: 28-days survival

    Time: Day 28

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

    Measure: Sequential organ failure assessment

    Time: Day 28

    Description: Markers of Infection

    Measure: C-reactive protein

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

    Description: Markers of Infection

    Measure: Procalcitonin

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

    Description: Marker of Immunological function

    Measure: Lymphocyte count

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

    Description: Marker of Immunological function

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

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

    Description: Marker of Immunological function

    Measure: CD4+/CD8+ratio

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

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

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

    Primary Outcomes

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

    Measure: Time to clinical recovery after treatment

    Time: within 14 days from the start of medication

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

    Measure: Rate of aggravation

    Time: within 14 days from the start of medication

    Secondary Outcomes

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

    Measure: Clinical remission rate

    Time: within 14 days from the start of medication

    Description: oxygenation index

    Measure: Dynamic changes of oxygenation index

    Time: within 14 days from the start of medication

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

    Measure: Time to cure

    Time: within 14 days from the start of medication

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

    Measure: rate to cure

    Time: within 14 days from the start of medication

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

    Measure: Time to defervescence

    Time: within 14 days from the start of medication

    Measure: Time to cough remission

    Time: within 14 days from the start of medication

    Measure: Time to dyspnea remission

    Time: within 14 days from the start of medication

    Measure: Days of supplemental oxygenation

    Time: within 14 days from the start of medication

    Measure: Rate of patients with requring supplemental oxygen

    Time: within 14 days from the start of medication

    Measure: Rate of patients with mechanical ventilation

    Time: within 14 days from the start of medication

    Measure: Time of negative COVID-19 nucleic acid results

    Time: within 14 days from the start of medication

    Measure: Rate of negative COVID-19 nucleic acid results

    Time: within 14 days from the start of medication

    Measure: Rate of ICU admission

    Time: within 14 days from the start of medication

    Measure: 28-day mortality

    Time: From the first day of screening to the day of follow-up (28 days)
    27 Assessing Health Related Quality of Life in Hypersensitivity Pneumonitis

    The objective of this study is to administer and validate a disease specific health related quality of life (HRQOL) survey for patients with Chronic Hypersensitivity Pneumonitis (CHP).

    NCT04273867
    Conditions
    1. Hypersensitivity Pneumonitis
    2. Chronic Hypersensitivity Pneumonitis
    3. Interstitial Lung Disease
    4. Extrinsic Allergic Alveolitis
    5. Health-related Quality of Life
    Interventions
    1. Other: Chronic Hypersensitivity Pneumonitis Health Related Quality of Life Survey Instrument
    MeSH:Lung Diseases Lung Diseases, Interstitial Pneumonia Alveolitis, Extrinsic Allergic Hypersensitivity
    HPO:Abnormal lung morphology Allergy Hypersensitivity pneumonitis Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: The newly developed survey that is being validated consists of 42 items that assess the impact that Hypersensitivity Pneumonitis has on daily life for those who have the disease.

    Measure: Validation of a health-related quality of life instrument for patients with Chronic Hypersensitivity Pneumonitis

    Time: Day 0

    Description: This survey will be used to assess the validity of the newly developed health-related quality of life instrument. This survey consists of 12 items. The average score for this survey has been calibrated to 50 with scores below 50 indicating a below average score and scores above 50 indicating an above average score.

    Measure: Validation of a health-related quality of life instrument for patients with Chronic Hypersensitivity Pneumonitis by administering the Short Form (SF-12) Survey

    Time: Day 0

    Description: This survey will be used to assess the validity of the newly developed health-related quality of life instrument. This survey consists of 15 items and is scored from 0-100 with 100 indicating good health.

    Measure: Validation of a health-related quality of life instrument for patients with Chronic Hypersensitivity Pneumonitis by administering the King's Brief Interstitial Lung Disease Questionnaire

    Time: Day 0

    Description: The newly developed survey will be administered again in 2 weeks following the first assessment.

    Measure: Change in Health-related Quality of Life Assessment Score

    Time: 2 weeks following Day 0
    28 Single Center, Single Arm, Open Clinical Study to Access Safety and Initial Efficacy of Anti-CD147 Humanized Meplazumab for Injection to Treat With 2019-nCoV Pneumonia

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

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

    Primary Outcomes

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

    Measure: 2019 nCoV nucleic acid detection

    Time: 14 days

    Secondary Outcomes

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

    Measure: Recovery of body temperature

    Time: 14 days

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

    Measure: Recovery of resting respiratory rate

    Time: 14 days

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

    Measure: Recovery of SPO2

    Time: 14 days

    Description: Rate of lung imaging recovery

    Measure: Chest CT / chest film changes

    Time: 28 days

    Description: Rate of PaO2 / FiO2 recovery

    Measure: PaO2 / FiO2

    Time: 14 days

    Description: Days to reach the isolation release standard

    Measure: Time to reach the isolation release standard

    Time: 28 days

    Description: Rate of CRP, D-Dimer test recovery

    Measure: Changes of inflammatory immune status

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

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

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

    Primary Outcomes

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

    Measure: Clinical recovery time

    Time: Up to Day 14

    Secondary Outcomes

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

    Measure: Complete fever time

    Time: Up to Day 14

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

    Measure: Cough relief time

    Time: Up to Day 14

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

    Measure: Virus negative time

    Time: Up to Day 14

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

    Measure: Incidence of severe or critical neocoronavirus pneumonia

    Time: Up to Day 14
    30 Effecacy and Safety of Bevacizumab in Severe Patients With Covid-19: a Pilot Study (BEST-CP)

    The novel identified coronavirus (SARS-CoV-2) in 2019 causes an nationwide outbreak as well as public health crisis in China, and expands globally. Pulmonary edema is one of the most detrimental symptoms and usually presents in severe and critical coronavirus disease (COVID-19), resulting in dyspnea, acute lung injury (ALI) ,acute respiratory distress syndrome (ARDS), and even death. Recent evidence revealed higher levels of blood Vascular Endothelial Growth Factor (VEGF) in COVID-19 patients compared with healthy controls. VEGF is considered as the most potent vascular permeability inducers. Numerous studies have revealed that VEGF was a key factor and a potential therapeutic target in ALI and ARDS. Bevacizumab, an anti-VEGF drug, approved by the FDA on February 26, 2004 and widely used in clinical oncotherapy, is a promising drug for ALI/ARDS in COVID-19 through suppression of pulmonary edema.

    NCT04275414
    Conditions
    1. Coronavirus Infections
    Interventions
    1. Drug: Bevacizumab Injection
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

    Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

    Time: 24 hours

    Description: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

    Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio

    Time: 7 days

    Secondary Outcomes

    Description: The oxygen-support status includes 6 levels: mechanical ventilation, non-invasive ventilation, a transition status of alternate use of non-invasive ventilation and high-flow oxygen, high-flow oxygen, low-flow oxygen and ambient air. The improvement of oxygen-support status is defined as switch from a higher level of oxygen-support to a lower level.

    Measure: Rate of improvement of oxygen-support status

    Time: 28 days

    Description: The areas of pulmonary lesions are analysised by a professional imaging software.

    Measure: The change of areas of pulmonary lesions shown on chest radiological imaging (chest CT or X-ray)

    Time: 7 days

    Description: Blood lymphocyte counts

    Measure: Blood lymphocyte counts

    Time: 7 days

    Description: Level of CRP

    Measure: Level of CRP

    Time: 7 days

    Description: Level of hs-CRP

    Measure: Level of hs-CRP

    Time: 7 days

    Description: All-cause mortality

    Measure: All-cause mortality

    Time: 28 days

    Description: Discharge rate

    Measure: Discharge rate

    Time: 28 days
    31 A Pilot Clinical Study on Aerosol Inhalation of the Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in the Treatment of Severe Patients With Novel Coronavirus Pneumonia

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

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

    Primary Outcomes

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

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

    Time: Up to 28 days

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

    Measure: Time to clinical improvement (TTIC)

    Time: Up to 28 days

    Secondary Outcomes

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

    Measure: Number of patients weaning from mechanical ventilation

    Time: Up to 28 days

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

    Measure: Duration (days) of ICU monitoring

    Time: Up to 28 days

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

    Measure: Duration (days) of vasoactive agents usage

    Time: Up to 28 days

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

    Measure: Duration (days) of mechanical ventilation supply

    Time: Up to 28 days

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

    Measure: Number of patients with improved organ failure

    Time: Up to 28 days

    Description: Rate of mortality within 28 days

    Measure: Rate of mortality

    Time: Up to 28 days

    Other Outcomes

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

    Measure: Sequential organ failure assessment (SOFA) score

    Time: Every day for 28 days

    Description: Records of Blood routine test

    Measure: Lymphocyte Count (10E9/L)

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

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

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

    Measure: Lactate dehydrogenase (U/L)

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

    Description: Coagulation function

    Measure: D-dimer (mg/L)

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

    Description: Records of heart failure

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

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

    Description: Record of serum cytokine

    Measure: IL-1β (pg/ml)

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

    Description: Record of serum cytokine

    Measure: IL-2R (ng/L)

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

    Description: Record of serum cytokine

    Measure: IL-6 (ng/L)

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

    Description: Record of serum cytokine

    Measure: IL-8 (ng/L)

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

    Description: Computed tomography or X-ray

    Measure: Chest imaging

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

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

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

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

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

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

    Primary Outcomes

    Description: Evaluation of pneumonia improvement

    Measure: Improvement of clinical symptoms including duration of fever

    Time: Measured from day 0 through day 28

    Description: Evaluation of pneumonia improvement

    Measure: Improvement of clinical symptoms including respiratory frequency

    Time: Measured from day 0 through day 28

    Description: Safety evaluation

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

    Time: Measured from day 0 through day 28

    Secondary Outcomes

    Description: Marker for 2019-nCoV

    Measure: Time of virus nucleic acid test negative

    Time: Measured from day 0 through day 28

    Description: Marker of immunological function

    Measure: CD4+ and CD8+ T cell count

    Time: Measured from day 0 through day 28

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: Day 28

    Description: Recovery of lung injury

    Measure: Size of lesion area by thoracic imaging

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

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

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

    Primary Outcomes

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

    Measure: Screening accuracy

    Time: 1 month

    Secondary Outcomes

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

    Measure: Cost-effectiveness analysis

    Time: 1 month
    34 A Randomized, Open-label Study to Evaluate the Efficacy and Safety of Pirfenidone in Patients With Severe and Critical Novel Coronavirus Infection

    The acute lung injury caused by SARS and 2003 were both related to the inflammatory cytokine storm in patients. The biochemical test showed abnormal increase in related indicators such as interleukin-8, and CT images showed a medical "white" lung". According to the experience of SARS treatment in 2003, the use of hormones will indeed help the patients to alleviate their illness, but patients who survived SARS either had too much hormone at that time and took too long. Although the lungs could recover, but the femoral head was necrotic Either the amount of hormones was very conservative at the time, which kept the lungs in the storm of inflammatory factors, leading to the emergence of irreversible pulmonary fibrosis. So is there a medicine that can anti-inflammatory, reduce the load of hormone use, and have the effect of treating and preventing pulmonary fibrosis complicated by severe viral lung? At present, pirfenidone has achieved encouraging results in the treatment of idiopathic Pulmonary Fibrosis (CTD-ILD) diseases. It is particularly encouraging that the values announced at the 2019 ATS Annual Conference suggest that pirfenidone has more anti-inflammatory and anti-oxidant effects than its own outstanding anti-fibrotic ability. The data shows early use, Its strong anti-SOD activity can effectively inhibit IL-1beta and IL-4, and can open the prevention mode of pulmonary interstitial fibrosis. Based on the above, this project intends to make the following scientific assumptions: based on the homology of the pathogens of the new coronavirus-infected pneumonia and the coronavirus infection of pneumonia in 2003, the similarities in the occurrence and development of the disease, that is, the pulmonary inflammatory storm occurs first, and thereafter The progress of fibrosis and the progressive decline of lung function and mortality are higher than those of ordinary pneumonia. We hope that by adding pirfenidone as a treatment program in addition to standard treatment, it will be a new and severe type of coronavirus infection. Patient clinical treatment provides an effective and practical method.

    NCT04282902
    Conditions
    1. Novel Coronavirus Pneumonia
    2. Pneumonia
    3. Pirfenidone
    Interventions
    1. Drug: pirfenidone
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Lesion area of chest CT image at 4 weeks

    Measure: chest CT

    Time: 4 weeks

    Description: Absolute change in pulse oxygen from baseline

    Measure: Finger pulse oxygen

    Time: 4 weeks

    Description: Absolute change in blood gas from baseline

    Measure: blood gas

    Time: 4 weeks

    Description: Absolute change in total score of King's brief questionnaire for interstitial Absolute change in total score of King's brief questionnaire for interstitial pulmonary disease (k-bild) from baseline at week 4

    Measure: K-BILD

    Time: 4 weeks

    Secondary Outcomes

    Description: Time to death within 4 weeks due to respiratory problems

    Measure: death

    Time: 4 weeks

    Description: Time to disease progression or death within 4 weeks

    Measure: Time to disease progression or death within 4 weeks

    Time: 4 weeks

    Description: lymphocyte count

    Measure: blood

    Time: 4 weeks

    Description: Absolute change in viral nucleic acid from baseline

    Measure: viral nucleic acid

    Time: 4 weeks

    Description: Pulmonary fibrosis survival symptoms absolute changes in dyspnea score from baseline

    Measure: dyspnea score

    Time: 4 weeks

    Description: changes in blood inflammatory indexes

    Measure: blood

    Time: 4 weeks

    Description: Absolute change in cough scores for pulmonary fibrosis survival symptoms from baseline

    Measure: cough scores

    Time: 4 weeks
    35 Study for Clinical Epidemiology and Methods of Diagnosis and Treatment of Novel Coronavirus Pneumonia (NCP)

    To develop practical and effective clinical diagnosis and treatment schemes for the control of novel coronavirus pneumonia.

    NCT04283396
    Conditions
    1. Novel Coronavirus Pneumonia
    Interventions
    1. Combination Product: systemic treatment
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of patients recover from novel coronavirus pneumonia

    Measure: recovery

    Time: up to 24 weeks
    36 CT Scores Predict Mortality in 2019-nCoV Pneumonia

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

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

    Primary Outcomes

    Measure: 7-day mortality

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

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

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

    Primary Outcomes

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

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

    Time: Day -1 to 10

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

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

    Time: Day -1 to 10

    Secondary Outcomes

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

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

    Time: Day -1 to 10

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

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

    Time: Day -1, 3, 7 and 10

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

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

    Time: Day -1, 3, 7 and 10

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

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

    Time: Day -1, 3, 7 and 10

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

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

    Time: Day -1, 3, 7 and 10

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

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

    Time: Day -1 and 10

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

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

    Time: Day -1 and 10

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

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

    Time: Day -1 to 10

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

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

    Time: Day -1 to 10

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

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

    Time: Day -1 to 10

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

    Measure: The all-cause mortality rate

    Time: Day -1 to 10

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

    Measure: The proportion of patients with acidosis

    Time: Day -1 and 10

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

    Measure: The total duration of the patients in-hospital

    Time: Day -1 to 10

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

    Measure: The total duration of oxygen inhalation during treatment

    Time: Day -1 to 10

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

    Measure: The oxygen flow rate during treatment

    Time: Day -1 to 10

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

    Measure: The oxygen concentration during treatment

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

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

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

    Primary Outcomes

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

    Measure: Reduction in the incidence of intubation and mechanical ventilation

    Time: 28 days

    Secondary Outcomes

    Description: Mortality from all causes

    Measure: Mortality

    Time: 28 days

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

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

    Time: 7 days

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

    Measure: Time to clinical recovery

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

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

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

    Primary Outcomes

    Description: The mortality of COVID-19 in 28 days

    Measure: Mortality

    Time: 28 day

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

    Measure: The time interval of Nucleic acid detection become negative

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

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

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

    Primary Outcomes

    Description: Evaluation of Pneumonia change

    Measure: Size of lesion area by chest imaging

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

    Description: Evaluation of Pneumonia change

    Measure: Blood oxygen saturation

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

    Secondary Outcomes

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

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

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

    Measure: Sequential organ failure assessment

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

    Description: Number of participants with treatment-related adverse events

    Measure: Side effects in the UC-MSCs treatment group

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

    Description: Markers of the heart function

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

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

    Description: Markers of infection

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

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

    Description: Marker of Immunology and inflammation

    Measure: CD4+ and CD8+ T cells count

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

    Description: Marker of Immunology and inflammation

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

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

    Description: Markers of the heart function

    Measure: Concentration of the myocardial enzymes

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

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

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

    Primary Outcomes

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

    Measure: Clinical recovery time

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

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

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

    Primary Outcomes

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

    Measure: Success rate of intubation

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

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

    Measure: Infection rate of Anesthesiologist

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

    Secondary Outcomes

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

    Measure: Extubation time

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

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

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

    Primary Outcomes

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

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

    Time: 4 weeks

    Secondary Outcomes

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

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

    Time: 4 weeks

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

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

    Time: 4 weeks

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

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

    Time: 4 weeks

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

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

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

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

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

    Primary Outcomes

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

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

    Time: 14 days

    Secondary Outcomes

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

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

    Time: 7, 14, 28 and 360 days

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

    Measure: Changes of blood oxygen

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

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

    NCT04302688
    Conditions
    1. Pneumonitis
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: survival status as of February 24, 2020

    Measure: survival status

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

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

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

    Primary Outcomes

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

    Measure: The time from randomization to clinical improvement

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

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

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

    Primary Outcomes

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

    Time: Day 10

    Secondary Outcomes

    Measure: PaO2

    Time: up to 30 days

    Measure: blood oxygen saturation (SpO2)

    Time: up to 30 days

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

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

    Time: up to 30 days

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

    Measure: Time to Clinical Improvement (TTCI)

    Time: up to 30 days

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

    Time: up to 30 days

    Measure: Duration (hours) of invasive mechanical ventilation use

    Time: up to 30 days

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

    Time: up to 30 days

    Measure: Duration (days) of Oxygen use

    Time: up to 30 days

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

    Time: Day 10

    Measure: The counts/percentage of Lymphocyte

    Time: up to 30 days

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

    Time: up to 30 days

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

    Measure: The incidence of critical status conversion in 30 days

    Time: up to 30 days

    Measure: All-cause mortality within 30 days

    Time: up to 30 days

    Measure: Frequency of severe adverse drug events

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

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

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

    Primary Outcomes

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

    Measure: COVID-19 positive X-Rays

    Time: 6 months

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

    Measure: COVID-19 negative X-Rays

    Time: 6 months
    49 The Observational Study of Cardiac and Pulmonary Ultrasound and Evaluation of Treatment of Severe Patients With Novel Coronavirus Pneumonia

    Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia, and assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis. Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation.

    NCT04314271
    Conditions
    1. Novel Coronavirus Pneumonia
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia

    Measure: characteristics of cardiopulmonary ultrasound

    Time: 30 mins

    Secondary Outcomes

    Description: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis.

    Measure: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis.

    Time: 2-3weeks

    Other Outcomes

    Description: Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not

    Measure: evaluate two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation.

    Time: 3 hours
    50 Tocilizumab (RoActemra) as Early Treatment of Patients Affected by SARS-CoV2 (COVID-19) Infection With Severe Multifocal Interstitial Pneumonia

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

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

    Primary Outcomes

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

    Measure: arrest in deterioration of pulmonary function

    Time: 7days

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

    Measure: improving in pulmonary function

    Time: 7 days

    Secondary Outcomes

    Description: rate of patients needed of intubation

    Measure: need of oro-tracheal intubation

    Time: +7 days

    Description: rate of patients dead

    Measure: death

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

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

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

    Primary Outcomes

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

    Measure: Change in Clinical Condition

    Time: 10 days

    Secondary Outcomes

    Description: Evaluation of Pneumonia change

    Measure: Rate of mortality within 10-days

    Time: 10 days

    Description: Evaluation of Pneumonia change

    Measure: Change of Clinical symptoms - respiratory rate

    Time: 10 days

    Description: oxygen saturation

    Measure: Hypoxia

    Time: 10 days

    Description: oxygen saturation

    Measure: PaO2 / FiO2 ratio

    Time: 10 days

    Description: Marker of Immunological function

    Measure: CD4+ and CD8+ T cell count

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

    Description: PaO2 / FiO2 ratio

    Measure: Changes of blood oxygen

    Time: 10 days

    Description: Number of participants with treatment-related adverse events

    Measure: Side effects in the treatment group

    Time: 10 days

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

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

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

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

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

    Primary Outcomes

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

    Measure: Respiratory failure

    Time: 14 days

    Secondary Outcomes

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

    Measure: Occurence of bacterial superinfection

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

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

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

    Primary Outcomes

    Description: 1-month mortality is defined as the ratio of patients who will alive after 1month from study start out of those registered at baseline

    Measure: One-month mortality rate

    Time: up to 1 month

    Secondary Outcomes

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

    Measure: Interleukin-6 level

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

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

    Measure: Lymphocyte count

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

    Description: CRP is assessed by routinely used determination of CRP

    Measure: CRP (C-reactive protein) level

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

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

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

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

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

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

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

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

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

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

    Description: Thoracic CT scan or Chest XR

    Measure: Radiological response

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

    Description: Days of hospitalization

    Measure: Duration of hospitalization

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

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

    Measure: Remission of respiratory symptoms

    Time: up to 1 month

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

    Measure: Remission of respiratory symptoms

    Time: up to 1 month

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

    Measure: Remission of respiratory symptoms

    Time: up to 1 month

    Description: time to independence from oxygen therapy in days

    Measure: Remission of respiratory symptoms

    Time: up to 1 month
    54 Clinical Trial of Favipiravir Tablets Combine With Chloroquine Phosphate in the Treatment of Novel Coronavirus Pneumonia

    This study is a multi-centered, three-armed, randomized, double-blinded, controlled study, namely, the oral trial drug favipiravir tablets plus chloroquine phosphatetablets tablets group (combined group), the oral trial drug favipiravir tablets group (pirovir group), and the oral placebo treatment group (control group). The total number of enrolled cases in this study was set at 150. During the treatment, the clinical data of the subjects were collected, the changes of viral load and biochemical indicators were detected, and the outcome of the subjects was monitored. The main indicators of efficacy include improvement or recovery of respiratory symptoms and viral nucleic acid shedding. The rate of progression to severe disease, duration of fever, peripheral blood index and improvement time of pulmonary imaging were the secondary indicators to evaluate the efficacy. Statistical analysis was performed at the middle and final stages of the study to evaluate the efficacy and safety of favipiravir tablets combined with chloroquine phosphatetablets tablets in the treatment of novel coronavirus pneumonia.

    NCT04319900
    Conditions
    1. Novel Coronavirus Pnuemonia
    Interventions
    1. Drug: favipiravir tablets+chloroquine phosphatetablets tablets
    2. Drug: Favipiravir tablets
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time of improvement or recovery of respiratory symptoms

    Measure: Time of Improvement or recovery of respiratory symptoms

    Time: 10 days during the intervention period

    Description: Number of days from positive to negative for test of swab or sputum virus nucleic acid

    Measure: Number of days virus nucleic acid shedding

    Time: 10 days during the intervention period

    Description: Frequency of improvement or recovery of respiratory symptoms

    Measure: Frequency of Improvement or recovery of respiratory symptoms

    Time: 10 days during the intervention period

    Secondary Outcomes

    Description: Duration of fever after recruitment

    Measure: Duration of fever

    Time: 10 days during the intervention period

    Description: Disease is defined as severe if it meets any of the following criteria: 1.Respiratory rate ≥30/min; 2. Oxygen saturation ≤93%; 3. Arterial partial oxygen pressure (PaO2)/oxygen absorption concentration (FiO2) ≤300 mmHg (1 mmHg=0.133 kPa)

    Measure: Frequencies of progression to severe illness

    Time: 10 days during the intervention period

    Description: Time of improvement of pulmonary imaging

    Measure: Time of improvement of pulmonary imaging

    Time: 10 days during the intervention period

    Description: Peripheral blood c-reactive protein concentration

    Measure: Peripheral blood c-reactive protein concentration

    Time: day-1,3,7,14 after the intervention period

    Description: Absolute value of peripheral blood lymphocytes

    Measure: Absolute value of peripheral blood lymphocytes

    Time: day-1,3,7,14 after the intervention period

    Description: percentage of peripheral blood lymphocytes

    Measure: percentage of peripheral blood lymphocytes

    Time: day-1,3,7,14 after the intervention period
    55 Automated Oxygen Titration - Monitoring and Weaning in Patients With Infectious Pneumonia Requiring Oxygen - Impact on the Number of Interventions for Healthcare Workers. An Innovative Device to Manage Patients With COVID-19 Pneumonia COVID Study (Closed-Loop Oxygen to Verify That Healthcare Workers Interventions Decreaseduring Pneumonia)

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

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

    Primary Outcomes

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

    Measure: The number of interventions

    Time: Hour0 to Hour4

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

    Measure: Duration of interventions

    Time: Hour0 to Hour24

    Secondary Outcomes

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

    Measure: Mean oxygen flow

    Time: Hour0 to Hour24 (1 day)

    Description: Time within SpO2 between 90 and 94%

    Measure: Time within theSpO2 target

    Time: Hour0 to Hour24 (1 day)

    Description: Time within SpO2 < 88%

    Measure: Time with hypoxemia

    Time: Hour0 to Hour24 (1 day)

    Description: Time within SpO2 > 96%

    Measure: Time with hyperoxemia

    Time: Hour0 to Hour24 (1 day)

    Description: Rate of ICU admission

    Measure: Rate of ICU admission

    Time: Hour0 to Hour24 (1 day)

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

    Measure: Rate of needed non invasive respiratory support

    Time: Hour0 to Hour24 (1 day)

    Description: Rate of intubation

    Measure: Rate of intubation

    Time: Hour0 to Hour24 (1 day)

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

    Measure: NEWS 2 score evolution

    Time: Hour0 to Hour24 (1 day)

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

    Measure: EWSO2 score evolution

    Time: Hour0 to Hour24 (1 day)

    Description: Cost effectiveness ratio (cost per SpO2 unit)

    Measure: Cost-effectiveness

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

    Description: Duration of the hospital length of stay

    Measure: length of stay

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

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

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

    Primary Outcomes

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

    Time: Day 28

    Secondary Outcomes

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

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

    Time: Up to 60 days

    Measure: Incidence of Mechanical Ventilation

    Time: Up to 60 days

    Measure: Ventilator-Free Days to Day 28

    Time: Up to Day 28

    Measure: Incidence of Intensive Care Unit (ICU) Stay

    Time: Up to 60 days

    Measure: Duration of ICU Stay

    Time: Up to 60 days

    Measure: Time to Clinical Failure

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

    Measure: Mortality Rate

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

    Measure: Time to Hospital Discharge

    Time: Up to 60 days

    Measure: Time to Recovery

    Time: Up to 60 days

    Measure: Duration of Time on Supplemental Oxygen

    Time: Up to 60 days

    Measure: Percentage of Participants with Adverse Events

    Time: Up to 60 days

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

    Time: Up to 60 days

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

    Time: Up to 60 days

    Measure: Proportion of Participants with Post-Treatment Infection

    Time: Up to 60 days

    Measure: Serum Concentration of IL-6

    Time: Up to 60 days

    Measure: Serum Concentration of sIL-6R

    Time: Up to 60 days

    Measure: Serum Concentration of Ferritin

    Time: Up to 60 days

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

    Time: Up to 60 days

    Measure: Serum Concentration of TCZ

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

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

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

    Primary Outcomes

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

    Measure: Evaluation of the clinical status

    Time: 15 days after randomization

    Secondary Outcomes

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

    Measure: All-cause mortality

    Time: 29 days after randomization

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

    Measure: Evaluation of the clinical status

    Time: 7 and 29 days after randomization

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

    Measure: Number of days free from mechanical ventilation

    Time: 29 days after randomization

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

    Measure: Duration of mechanical ventilation

    Time: 29 days after randomization

    Description: Length of hospital stay on survivors

    Measure: Duration of hospitalization

    Time: 29 days after randomization

    Description: Presence of other secondary infections

    Measure: Other secondary infections

    Time: 29 days after randomization

    Description: Time from treatment start to death

    Measure: Time from treatment start to death

    Time: 29 days after randomization

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

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

    Time: 3, 6, 9 and 12 months

    Description: Leucocyte transcriptome

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

    Time: Baseline

    Other Outcomes

    Description: Occurrence of QT interval prolongation

    Measure: QT interval prolongation

    Time: 29 days after randomization

    Description: Occurrence of gastrointestinal intolerance

    Measure: Gastrointestinal intolerance

    Time: 29 days after randomization

    Description: Occurrence of laboratory hematimetric parameters, creatinine and bilirubin

    Measure: Laboratory abnormalities

    Time: 29 days after randomization

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

    Measure: Adverse events

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

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

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

    Primary Outcomes

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

    Measure: Lung ultrasound grading system for COVID-19 pneumonia

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

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

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

    Primary Outcomes

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

    Measure: Clinical improvement

    Time: Day 28

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

    Measure: Hospital discharge

    Time: Day 28

    Secondary Outcomes

    Description: Number of death patients

    Measure: Death

    Time: Day 28

    Description: 7-category ordinal scale

    Measure: Clinical status

    Time: Day 7, Day 14

    Description: Number of patients with mechanical ventilhation

    Measure: Mechanical ventilhation

    Time: Day 28

    Description: Days of hospitalization

    Measure: Hospitalization

    Time: Day 28

    Description: Days to death from treatment initiation

    Measure: Time from treatment initiation to death

    Time: Day 28

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

    Measure: Time to Negativization COVID 19

    Time: Day 21

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

    Measure: Fever

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

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

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

    Primary Outcomes

    Description: Change of hospital mortality

    Measure: In-hospital mortality

    Time: 72 hours

    Secondary Outcomes

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

    Measure: PCR levels

    Time: 72 hours

    Description: Change of the lactate clearance

    Measure: Lactate clearance

    Time: 72 hours

    Description: Change of hospital stay days

    Measure: Hospital stay

    Time: 72 hours

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

    Measure: Symptoms

    Time: 72 hours

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

    Measure: Positive swab

    Time: 72 hours

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

    Measure: Tomography imaging

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

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

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

    Primary Outcomes

    Description: proportion of deaths at day 28 between groups compared

    Measure: Mortality rate reduction of 50% by day 28

    Time: 28 days after randomization

    Secondary Outcomes

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

    Measure: Absolute mortality on days 7 and 14

    Time: 7 and 14 days after first dose

    Description: clinical status

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

    Time: 14 and 28 days after first dose

    Description: clinical status

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

    Time: during and after intervention, up to 28 days

    Description: supplemental oxygen

    Measure: Duration of supplemental oxygen (if applicable)

    Time: during and after intervention, up to 28 days

    Description: mechanical ventilation

    Measure: Duration of mechanical ventilation (if applicable)

    Time: during and after intervention, up to 28 days

    Description: hospitalization

    Measure: Absolute duration of hospital stay in days

    Time: during and after intervention, up to 28 days

    Description: adverse events grade 3 and 4

    Measure: Prevalence of grade 3 and 4 adverse events

    Time: during and after intervention, up to 28 days

    Description: adverse events

    Measure: Prevalence of serious adverse events

    Time: during and after intervention, up to 28 days

    Description: increase or decrease in serum creatinine compared to baseline

    Measure: Change in serum creatinine level

    Time: during and after intervention, up to 28 days

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

    Measure: Change in serum troponin I level

    Time: during and after intervention, up to 28 days

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

    Measure: Change in serum aspartate aminotransferase level

    Time: during and after intervention, up to 28 days

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

    Measure: Change in serum CK-MB level

    Time: during and after intervention, up to 28 days

    Description: virus clearance from respiratory tract secretion

    Measure: Change in detectable viral load in respiratory tract swabs

    Time: during and after intervention, up to 28 days

    Description: viremia in blood detected through RT-PCR

    Measure: Viral concentration in blood samples

    Time: during and after intervention, up to 28 days

    Description: death

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

    Time: during and after intervention, up to 28 days
    62 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
    63 Cytokine Adsorption in Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation

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

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

    Primary Outcomes

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

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

    Time: 72 hours

    Secondary Outcomes

    Description: survival after 30 days

    Measure: 30-day-survival

    Time: 72 hours

    Description: needed dosage of norepinephrine and other vasopressors

    Measure: vasopressor dosage

    Time: 72 hours

    Description: fluid balance levels during cytokine adsorption

    Measure: fluid balance

    Time: 72 hours

    Description: serum-lactate levels during cytokine adsorption

    Measure: lactate

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

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

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

    Primary Outcomes

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

    Measure: rate of recovery

    Time: 3 weeks

    Secondary Outcomes

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

    Measure: time to improvement

    Time: 3 weeks

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

    Measure: efficacy of treatments

    Time: 3 weeks

    Description: liver, kidney or multiorgan failure, cardiac failure

    Measure: organ failure

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

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

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

    Primary Outcomes

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

    Measure: Protection against COVID-19

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

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

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

    Primary Outcomes

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

    Time: within 24 hours of admission to ICU

    Secondary Outcomes

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

    Measure: Coinfections

    Time: during ICU stay, up to 28 days

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

    Measure: Respiratory dysfunction requiring mechanical ventilation

    Time: during ICU stay, up to 28 days

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

    Measure: Sequential Organ Failure Assessment (SOFA) Score

    Time: during ICU stay, up to 28 days

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

    Measure: SAPS II score

    Time: at admission

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

    Measure: Disseminated Intravascular Coagulation (DIC) score

    Time: during ICU stay, up to 28 days

    Measure: Number of days on vasopressive amines

    Time: during ICU stay, up to 28 days

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

    Time: during ICU stay, up to 28 days

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

    Time: during ICU stay, up to 28 days

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

    Time: At 28 day

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

    Measure: Short Form 36

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

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

    Measure: Hospital anxiety and depression scale (HADS)

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

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

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

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

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

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

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

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

    Measure: Modified Medical Research Council (MMRC) Dyspnea Scale

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

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

    Time: until day 28 after admission of ICU

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

    Measure: Viral clearance

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

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

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

    Primary Outcomes

    Description: breath sample collection

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

    Time: up to daily during hospital admission

    Secondary Outcomes

    Description: breath sample collection

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

    Time: multiple samples up to 60 days

    Description: breath sample collection

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

    Time: multiple samples up to 60 days

    Description: breath sample collection

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

    Time: multiple samples up to 60 days

    Description: breath sample collection

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

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

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

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

    Primary Outcomes

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

    Time: 29 days

    Secondary Outcomes

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

    Measure: Days of hospitalization among survivors at 29 days.

    Time: 29 days

    Measure: Mortality rate from any cause at 29 days.

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

    Time: 29 days

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    Primary Outcomes

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

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

    Time: 18 months

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

    Measure: Factors associated with severe COVID-19 outcomes

    Time: 18 months

    Secondary Outcomes

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

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

    Time: 18 months

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

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

    Time: 18 months
    70 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
    71 A Single Arm Open-label Clinical Study to Investigate the Efficacy and Safety of Ruxolitinib for the Treatment of COVID-19 Pneumonia

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

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

    Primary Outcomes

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

    Time: 6 months

    Measure: Number of adverse events

    Time: 9 months

    Secondary Outcomes

    Measure: All cause mortality rate

    Time: 9 months

    Measure: Average duration of hospital stay

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

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

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

    Primary Outcomes

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

    Measure: Clinical response

    Time: Assessed for the 24 hour period after tocilizumab administration

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

    Measure: Biochemical response

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

    Secondary Outcomes

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

    Measure: Overall survival

    Time: 28 days

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

    Measure: Survival to hospital discharge

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Progression of COVID-19 pneumonitis

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Rate of non-elective mechanical ventilation

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Duration of mechanical ventilation

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Time to mechanical ventilation

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

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

    Measure: Rate of vasopressor/inotrope utilization

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Duration of vasopressor/inotrope utilization

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Time to vasopressor or inotropic utilization

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

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

    Measure: Number of ICU days

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

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

    Measure: Duration of Increased Supplemental Oxygen Requirement from Baseline

    Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration
    73 Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study

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

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

    Primary Outcomes

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

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

    Time: 14 days

    Secondary Outcomes

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

    Time: 24 hours

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

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

    Time: 14 days

    Description: days

    Measure: Duration of hospitalization

    Time: 14 days

    Description: days

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

    Time: 14 days

    Description: number/microliter

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

    Time: 7, 14 days

    Description: number/microliter

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

    Time: 7, 14 days

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

    Time: 7, 14 days

    Measure: Changes from the baseline of Ferritin values

    Time: 7, 14 days

    Measure: Changes from the baseline of BNP values

    Time: 7,14 days

    Measure: Changes from the baseline of CK-MB values

    Time: 7,14 days

    Measure: Changes from the baseline of Troponin values

    Time: 7,14 days

    Measure: Changes from the baseline of LDH values

    Time: 7,14 days

    Measure: Changes from the baseline of myoglobulin values

    Time: 7,14 days

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

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

    Time: 7,14 days

    Measure: Rate of adverse events report during and after tocilizumab

    Time: 14 days

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

    Time: 12 weeks

    Measure: Percentage of patients who develop autoimmune diseases

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

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

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

    Primary Outcomes

    Description: reduction in oxygen and ventilation support

    Measure: reduction in oxygen and ventilation support

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

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

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

    Primary Outcomes

    Description: 28-day all-cause mortality

    Measure: Mortality

    Time: Day 28

    Secondary Outcomes

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

    Measure: Treatment Emergent Adverse Events

    Time: Day1 to Day 60

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

    Measure: Safety Parameters

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

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

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

    Primary Outcomes

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

    Measure: Number of antibiotic free days

    Time: Day 28

    Secondary Outcomes

    Measure: Mortality rates

    Time: Day 28 and Day 90

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

    Time: day 28

    Description: Total exposure to antibiotics

    Measure: Antibiotics duration at D28

    Time: Day 28

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

    Time: Day 28

    Measure: Incidence rates of bacterial super-infections

    Time: day 28

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

    Time: Day 28

    Measure: ICU and hospital lengths of stay

    Time: Day 28

    Description: using a quality of life questionnaire (EQ5D5L)

    Measure: Quality of life Quality of life

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

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

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

    Primary Outcomes

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

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

    Time: at day0

    Secondary Outcomes

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

    Time: at day0

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

    Time: at day0

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

    Time: at day5

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

    Time: at day15

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

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

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

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

    Primary Outcomes

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

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

    Time: 14 days

    Secondary Outcomes

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

    Measure: Adverse events

    Time: 7 days

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

    Measure: duration of hospitalization

    Time: 14 days

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

    Measure: systemic inflammation

    Time: 14 days

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

    Measure: overall survival

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

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

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

    Primary Outcomes

    Description: Assessed by hospital records

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

    Time: through day 14 after study treatment initiation

    Secondary Outcomes

    Description: Assessed by hospital records

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

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

    Description: Assessed by hospital records

    Measure: Number of days of patient hospitalization

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

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

    Measure: Change from baseline in organ failure parameters

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

    Description: Determined as percentage of dead patients

    Measure: Proportion of mortality rate

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

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

    Measure: Analysis of the remission of respiratory symptoms

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

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

    Measure: Evaluation of the radiological response

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

    Description: determined using oropharyngeal or anal swabs

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

    Time: within 28 days from study inclusion

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

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

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

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

    Measure: Change from baseline of hemoglobin

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

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

    Measure: Change from baseline of platelets

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

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

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

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

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

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

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

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

    Measure: Change from baseline of creatinine

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

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

    Measure: Change from baseline of glucose

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

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

    Measure: Change from baseline of total bilirubin

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

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

    Measure: Change from baseline of albumin

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

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

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

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

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

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

    Primary Outcomes

    Description: Mortality 30 days following hospital admission

    Measure: Hospital mortality

    Time: 30 days

    Secondary Outcomes

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

    Measure: Length of stay in the intensive care unit

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

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

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

    Primary Outcomes

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

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

    Time: within 2 weeks after first subject included

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

    Measure: Inter-observer variability

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

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

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

    Primary Outcomes

    Description: Improvement and recovery time of inflammatory and immune factors

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

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

    Description: Evaluation of Pneumonia change

    Measure: Blood oxygen saturation

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

    Secondary Outcomes

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

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

    Description: Evaluation of Pneumonia change

    Measure: Size of lesion area by chest imaging

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

    Description: Marker of Immunology and inflammation

    Measure: CD4+ and CD8+ T cells count

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

    Description: Degree of infection

    Measure: Peripheral blood count recovery time

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

    Description: Indirect response to lung function

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

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

    Description: Clearance time of COVID-19 in participant

    Measure: COVID-19 nucleic acid negative time

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

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

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

    Primary Outcomes

    Description: Mortality at day 28

    Measure: Mortality at day 28

    Time: day 28

    Secondary Outcomes

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

    Measure: severe complications

    Time: up to day 28

    Description: Delay in imaging in hours

    Measure: Imaging

    Time: day 1

    Description: delay in microbiological diagnosis in hours

    Measure: Delay in Microbiological diagnosis

    Time: day 1

    Description: Antiviral therapy Yes / no

    Measure: Antiviral therapy

    Time: up to day 28

    Description: Antibiotic therapy Yes / No

    Measure: Antibiotic therapy

    Time: day 28

    Description: Covid-19 treatments Yes / No

    Measure: Covid-19 treatments

    Time: up to day 28

    Description: number

    Measure: Patients receiving renal replacement therapy

    Time: up to day 28

    Description: number

    Measure: Patients receiving mechanical ventilation

    Time: up to day 28

    Description: Patient alive at day 28 : yes / No

    Measure: Vital status

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

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

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

    Primary Outcomes

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

    Measure: PTSD Family members sup 22

    Time: 90 days

    Secondary Outcomes

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

    Measure: PTSD Family members

    Time: 90 days

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

    Measure: PTSD Patients

    Time: 90 days

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

    Measure: PTSD healthcare providers

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

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

    Measure: HADS Family members

    Time: 90 days

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

    Measure: HADS Patients

    Time: 90 days

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

    Measure: SF36 Patients

    Time: 90 days

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

    Measure: Questionnaire Family members

    Time: 90 days

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

    Measure: Questionnaire Patients

    Time: 90 days

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

    Measure: Questionnaire healthcare providers

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

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

    Measure: MBI healthcare providers

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

    Description: Job Strain as assessed by the Karasec instrument

    Measure: Karasec instrument healthcare providers

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

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

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

    Primary Outcomes

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

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

    Time: 28 days

    Secondary Outcomes

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

    Measure: Proportion of patients who require escalation in care

    Time: 14 days

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

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

    Time: 14 days

    Description: Survival to hospital discharge

    Measure: Proportion of patients surviving to hospital discharge

    Time: days

    Description: Incidence and type of adverse events

    Measure: Drug safety profile

    Time: 14 days

    Description: Number of days spent on advanced respiratory support measures

    Measure: Duration of advanced respiratory support

    Time: days

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

    Measure: Duration of hospital stay

    Time: days

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

    Measure: Time from treatment initiation to death

    Time: days

    Description: Time (in days) to resolution of fever

    Measure: Time to resolution of fever

    Time: 14 days

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

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

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

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

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

    Primary Outcomes

    Description: description of ultrasound abnormalities for Covid-19 patients

    Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

    Time: Day one

    Secondary Outcomes

    Description: description of ultrasound abnormalities for Covid-19 patients

    Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

    Time: Day 3

    Description: description of ultrasound abnormalities for Covid-19 patients

    Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

    Time: Day 14

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

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

    Time: Day 1

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

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

    Time: Day 3

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

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

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

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

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

    Primary Outcomes

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

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

    Time: 7 days after randomization

    Secondary Outcomes

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

    Measure: Mortality rate

    Time: after randomization, up to 28 days

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

    Measure: Number of participants in need of intensive care support

    Time: during and after intervention, up to 28 days

    Description: Viral load change in blood and oropharyngeal swab samples

    Measure: Viral concentration

    Time: After randomization, up to 7 days

    Description: Incidence of serious adverse events during and after treatment

    Measure: Cumulative incidence of serious adverse events

    Time: During and after intervention, up to 28 days

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

    Measure: Cumulative incidence of grade 3 and 4 adverse events

    Time: During and after intervention, up to 28 days

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

    Measure: Proportion of patients with discontinued treatment

    Time: after randomization, up to 28 days

    Description: proportion of patients with increased levels of troponin I

    Measure: Incidence of cardiac lesions

    Time: after randomization, up to 120 days

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

    Measure: Incidence of cardiac disfunctions

    Time: after randomization, up to 120 days

    Description: Changes measured on day 120 will be compared to baseline, through spirometry.

    Measure: Change in respiratory capacity

    Time: Day 120 after randomization
    88 A Randomized, Double-blind, Placebo-controlled, Clinical Trial of LY3127804 in Patients Who Are Hospitalized With Pneumonia and Presumed or Confirmed COVID-19

    A randomized, double-blind, placebo-controlled, clinical trial of LY3127804 in participants who are hospitalized with pneumonia and presumed or confirmed COVID-19. The study may last up to 9 weeks and include daily visits up to day 28, and follow-up visits by phone.

    NCT04342897
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Drug: LY3127804
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of days on which a participant breathes without assistance

    Measure: Number of Ventilator Free Days

    Time: Day 1 to Day 28

    Secondary Outcomes

    Description: The scale is an assessment of clinical status. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities

    Measure: Number of Participants Reporting Each Severity Rating on the National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Assessment

    Time: Day 1 to Day 28

    Description: Survival without Respiratory Failure

    Measure: Percentage of Participants who are Alive and Respiratory Failure Free

    Time: Day 1 to Day 28

    Description: Mortality

    Measure: Mortality

    Time: Day 1 to Day 28

    Description: Days of Hospitalization

    Measure: Length of Hospitalization

    Time: Day 1 to Day 28

    Description: Number of Participants with any Serious Adverse Event (SAE)

    Measure: Number of Participants with any Serious Adverse Event (SAE)

    Time: Day 1 to Day 28

    Description: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

    Measure: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

    Time: Day 1 to Day 28
    89 Efficacy of Injectable Methylprednisolone Sodium Succinate in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome Under the New Coronavirus (SARS-CoV2): a Phase IIb, Randomized, Double-blind, Placebo-controlled, Clinical Trial.

    This is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 416 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MP (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

    NCT04343729
    Conditions
    1. SARS-CoV Infection
    2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    Interventions
    1. Drug: Methylprednisolone Sodium Succinate
    2. Drug: Placebo solution
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Mortality rate on day 28, after randomization

    Measure: Mortality rate at day 28

    Time: on day 28, after randomization

    Secondary Outcomes

    Description: Proportion of patient that died on days 7, 14 and 28.

    Measure: Mortality rate on days 7, 14 and 28

    Time: after randomization, up to 28 days.

    Description: proportion of patients requiring orotracheal intubation

    Measure: Incidence of orotracheal intubation

    Time: after randomization, up to 7 days.

    Description: Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.

    Measure: Change in oxygenation index

    Time: after randomization, up to 7 days.
    90 Corticosteroids During Covid-19 Viral Pneumonia Related to SARS-Cov-2 Infection

    Infection with the SARS-Cov-2 virus, responsible of severe acute respiratory distress syndrome (SARS), is an emerging infectious disease called Covid-19 and declared as pandemic by the World Health Organization on March 11, 2020. This pandemic is responsible of significant mortality. In France, several thousand patients are hospitalized in intensive care units, and their number continues to increase. Mortality during Covid-19 is mainly linked to acute respiratory distress syndrome, which frequency is estimated in France to occur in 6% of infected patients. Comorbidities such as cardiovascular conditions, obesity and diabetes increase susceptibility to severe forms of Covid-19 and associated mortality. Therapeutic management has three components: symptomatic management, including supplementary oxygen therapy and in case of respiratory distress mechanical ventilation; the antiviral approach; and immunomodulation, aiming at reducing inflammation associated with viral infection, which is considered to take part in severe presentations of the disease. During Covid-19 viral pneumonia related to SARS-COv-2, there is a significant release of pro-inflammatory cytokines in the acute phase of viral infection, which could participate in viral pneumonia lesions. In children with less mature immune system than adults, SARS-Cov-2 infection is less severe. The current prevailing assumption is that severe forms of Covid-19 may not only be related to high viral replication, but also to an excessive inflammatory response favoring acute lung injury and stimulating infection. The investigators hypothesize that early control of the excessive inflammatory response may help reducing the risk of acute respiratory distress syndrome. The investigators will evaluate the benefit, safety and tolerability of corticosteroid therapy to reduce the rate of subjects hospitalized for Covid-19 viral pneumonia who experience clinical worsening with a need of high-flow supplemental oxygen supplementation or transfer in intensive care units for respiratory support.

    NCT04344288
    Conditions
    1. Viral Pneumonia Human Coronavirus
    2. COVID-19
    Interventions
    1. Drug: Prednisone
    2. Other: Control group
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask. measured twice at 5-15 min intervalsThe average value of the two measurements will be calculated.

    Measure: Number of patients with a theoretical respiratory indication for transfer to intensive care unit evaluated by a SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask.

    Time: 7 days

    Secondary Outcomes

    Description: level1: not hospitalized no limited activities, level 7: death

    Measure: disease severity assessed on a 7-level ordinal scale

    Time: 7 days

    Measure: number of patients with a supplemental oxygen use

    Time: 7 days

    Description: Reduction of radiological signs on chest imaging

    Measure: radiological signs on chest imaging

    Time: 7 days

    Measure: number of patients transferred to intensive care unit

    Time: 21 days

    Measure: number of patients requiring invasive ventilation

    Time: 21 days

    Description: duration on days

    Measure: Duration of oxygen therapy

    Time: 21 days

    Measure: number of adverse events induced by corticosteroid treatment

    Time: 21 days

    Measure: number of patients with infections other than SARS-CoV-2

    Time: 21 days

    Measure: number of deaths

    Time: 21 days
    91 Management by Hyperbaric Oxygen Therapy of Patients With Hypoxaemic Pneumonia With SARS-CoV-2 (COVID-19)

    Several patients with hypoxaemic SARS-CoV2 pneumonia were able to benefit from hyperbaric oxygen treatment (HBOT) in China. In a clinical case published in the Chinese journal of hyperbaric medicine, treatment with repeated HBO sessions prevented admission to intensive care unit with mechanical ventilation in a patient aged 69 who presented with signs of respiratory decompensation. HBOT is the most powerful oxygenation modality in the body today. HBOT can dramatically increase the amount of dissolved oxygen in the blood. HBOT not only promotes blood transport but also its tissue delivery. Furthermore, HBOT has specific immunomodulatory properties, both humoral and cellular, making it possible, for example, to reduce the intensity of the inflammatory response and to stimulate antioxidant defenses by repeating sessions. A virucidal capacity of HBOT might also be involved. HBOT is generally regarded as safe with very few adverse events. Following this feedback, it is proposed in the context of crisis management related to SARS-CoV2 to assess the value of HBO treatment of patients with CoV2 pneumonia. Indeed, it seems essential to propose therapeutic strategies to limit the risk of respiratory decompensation requiring admission to intensive care unit for patients with SARS-CoV2 pneumonia.

    NCT04344431
    Conditions
    1. Covid-19
    Interventions
    1. Combination Product: Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device)
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to normalize the oxygen requirement (oxygeno-dependence), i.e. allowing a pulse oximetry value in ambient air greater than or equal to 92% and / or arterial blood gas with a PaO2 value greater than 60mmHg in ambient air.

    Measure: Time to normalize the oxygen requirement (oxygeno-dependence)

    Time: 1 month

    Secondary Outcomes

    Description: Number of days with oxygen need, taking into account the predictors of bad outcome

    Measure: Days of hospitalization between the HBO group and the control group.

    Time: 1 month

    Description: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% between the OHB group and the control group.

    Measure: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% values between the HBO group and the control group.

    Time: 1 month

    Description: Days on invasive mechanical ventilation

    Measure: Days on invasive mechanical ventilation

    Time: 1 month

    Description: Mortality

    Measure: Mortality

    Time: 1 month

    Other Outcomes

    Description: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation

    Measure: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation

    Time: 1 month
    92 Microbial Etiology of Ventilator-associated Pneumonia (VAP) in COVID-19 Infected Patients

    National multicentric observational retrospective case-control study comparing the relative frequency of the various microorganisms responsible for VAP in patients infected or not by SARS-CoV-2 and their resistance to antibiotics.

    NCT04344509
    Conditions
    1. Ventilator Associated Pneumonia
    Interventions
    1. Other: Bacterial species isolated
    MeSH:Pneumonia, Ventilator-Associated Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Prevalence of the microorganisms responsible for VAP among patients infected or not by the SARS-CoV-2

    Time: 1 month

    Secondary Outcomes

    Measure: Prevalence of multi-drug resistant bacteria responsible for VAP among patients infected or not by the SARS-CoV-2

    Time: 1 month
    93 Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS

    The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality. Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival. The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.

    NCT04344730
    Conditions
    1. Acute Hypoxemic Respiratory Failure
    2. COVID-19
    Interventions
    1. Drug: Dexamethasone injection
    2. Drug: placebo
    3. Procedure: conventional oxygen
    4. Procedure: CPAP
    5. Procedure: HFNO
    6. Procedure: mechanical ventilation
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The time-to-death from all causes within the first 60 days after randomization.

    Measure: The time-to-death from all causes

    Time: day-60

    Description: the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.

    Measure: The time to need for mechanical ventilation (MV)

    Time: day-28.

    Secondary Outcomes

    Description: The cycle threshold for SARS-CoV-2 PCR at baseline, day 7 and day 10 in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)

    Measure: The viral load in the respiratory tract

    Time: day-10

    Description: Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28

    Measure: Number of patient with at least one episode of healthcare-associated infections

    Time: day-28

    Description: To compare the exposition to mechanical ventilation

    Measure: Number of days alive without mechanical ventilation

    Time: day-28

    Description: Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)

    Measure: Measure of SOFA score

    Time: day-28

    Description: to compare the exposition to renal replacement therapy

    Measure: Number of days alive without renal replacement therapy

    Time: day-28

    Description: To compare the lengths of ICU

    Measure: Lengths of ICU-stay

    Time: day-60

    Description: To compare the lengths of hospital-stay

    Measure: Lengths of hospital-stay

    Time: day-60

    Description: Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation

    Measure: Number of patients with severe hypoxemia,

    Time: day 60

    Description: Proportion of patients with cardiac arrest within 1 hour after intubation

    Measure: Number of patients with cardiac arrest within 1 hour after intubation

    Time: day 60
    94 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-COAG Trial

    COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent Covid-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. This protocol CORIMUNO19-COAG will evaluate the efficacy and safety of active anticoagulation using heparin: Tinzaparin (INNOHEP®) or unfractionated heparin (Calciparine®, Héparine Sodique Choay®) in COVID-19 patients hospitalized in conventional or intensive care units. It will use a phase 2 randomized open-label multicentre clinical trial, where patients will be randomly allocated to anticoagulation versus Standard of Care.

    NCT04344756
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Drug: Tinzaparin or unfractionated heparin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: group 1

    Measure: Survival without ventilation (VNI or mechanical ventilation)

    Time: day 14

    Description: group 2

    Measure: ventilator free survival

    Time: day 28

    Secondary Outcomes

    Description: range from 0 (healthy) to 10 (death) values below or equal to 5 correspond to the absence of any oxygen supply beside nasal or facial mask

    Measure: World Health Organisation(WHO) progression scale ≤5

    Time: day 4

    Description: range from 0 (healthy) to 10 (death)

    Measure: World Health Organisation(WHO) progression scale

    Time: day 4, 7 and 14

    Measure: overall survival

    Time: day 14, 28 and 90

    Measure: Length of hospital stay

    Time: day 28

    Measure: Length of ICU stay

    Time: day 28

    Measure: time to oxygenation supply independency

    Time: day 28

    Measure: time to ventilator (non invasive or invasive)

    Time: day 28

    Description: according to Acute Kidney Injury (AKIN) classification system

    Measure: rate of acute kidney injury

    Time: day 28

    Measure: time to Renal Replacement Therapy (RRT) initiation

    Time: day 28

    Description: confirmed by objective testing

    Measure: rate of clinically overt pulmonary embolism or proximal deep vein thrombosis

    Time: day 14 and day 90

    Description: confirmed by objective testing

    Measure: Rate of clinically overt arterial thrombosis

    Time: day 14 and day 90

    Measure: Rate of unscheduled central venous catheter replacement for catheter dysfunction

    Time: day 28

    Description: as a thrombus extending from the catheter into the lumen of the deep vein where the catheter is inserted diagnosed with radiologic imaging in case of a clinical suspicion of upper/lower limb DVT or pulmonary embolism or compulsory catheter removal

    Measure: Rate of central venous catheter-related deep vein thrombosis (CVC-DVT)

    Time: day 28

    Measure: Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction

    Time: day 28

    Measure: Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not

    Time: day 28

    Measure: Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

    Time: day 28

    Measure: Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

    Time: day 28

    Measure: Incidence of adverse events

    Time: day 28
    95 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-19- BEVA Trial

    Bevacizumab, ZERIBEV® (Pfizer)/AVASTIN® (Roche) 25 mg/ml ®, is a recombinant humanised monoclonal IgG1 antibody It seems interesting to use bevacizumab in severe patients infected with SARS-CoV-2 requiring hospitalization in conventional unit or in ICU. This protocol CORIMUNO19-BEVA will evaluate the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) COVID-19 patients hospitalized in conventional units. This phase 2 randomized clinical trial aimed at evaluating the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) alone versus standard of care (SoC) in patients hospitalized in conventional units.

    NCT04344782
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Drug: Bevacizumab Injection
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of surviving patients without need for intubation for respiratory support

    Time: day 14

    Secondary Outcomes

    Description: value of a healthy individual occurs between 95 - 100

    Measure: Saturation of Oxygen in the blood (SaO2)

    Time: day 14

    Description: value of a healthy individual occurs between 75-100 mmHg

    Measure: Arterial oxygen partial pressure (paO2)

    Time: day 14

    Description: Normal level should be >500 Index of severity of acute respiratory distress syndrome (ARDS) mild if 200-300 moderate if 100-200 severe if < 200

    Measure: Ratio of arterial oxygen partial pressure to fractional inspired oxygen (paO2/FiO2)

    Time: day 14

    Description: based on a Likert scale with scores ranging from 1 to 5 (1-definitely no; 2-probably no; 3-equivocal; 4-probably yes; 5-definitely yes)

    Measure: CT-scan score

    Time: day 14

    Description: measured on an visual analog scale (VAS), ranging from 0 (no dyspnea) to 10 (major dyspnea)

    Measure: dyspnea

    Time: day 28

    Measure: overall survival

    Time: day 14 and 28

    Measure: admissionn to the intensive care unit (ICU)

    Time: day 14 and day 28

    Measure: incidence of mechanical ventilation

    Time: day 14 and day 28

    Measure: hospital length of stay

    Time: day 28

    Measure: incidence of adverse event

    Time: day 28

    Measure: VEGF plasma concentration

    Time: day 28
    96 Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial

    This is an open label clinical study to evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection. The study aims to document possible prevention of pneumonia in patients staying at home and in improving the symptoms of SARS-CoV-2 pneumonia in patients who will be hospitalised.

    NCT04344951
    Conditions
    1. Pneumonia, Viral
    2. Covid-19
    Interventions
    1. Drug: UNIKINON (Chloroquine phosphate) 200mg tablets
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Achieving 50% reduction in symptom score for patients with lower respiratory tract infection on day 8 visit from study initiation.

    Measure: 50% reduction in symptom score for patients with lower respiratory tract infection

    Time: Day 8 visit from study initiation

    Description: Lack of progression to lower respiratory tract infection in patients enrolled in the study due to upper respiratory tract infection on day 8 visit from study initiation.

    Measure: Lack of progression for patients with upper respiratory tract infection

    Time: Day 8 visit from study initiation

    Secondary Outcomes

    Description: Lower respiratory tract infection rating takes place. The symptoms checked are: Cough, Chest pain, Dyspnea, expectoration. For each symptom score is given from 0 to 3 depending on the intensity and they are summed.

    Measure: Comparison of the primary endpoint with respective patients not receiving the treatment

    Time: Day 14 visit from study initiation

    Description: It is defined as the presence of both of the following: Respiratory quotient (pO2 / FiO2) less than 150 Need for treatment with CPAP or mechanical ventilation

    Measure: Serious respiratory failure until day 14. This will be compared with respective patients not receiving the treatment.

    Time: Day 14 visit from study initiation

    Description: Frequency of AEs and SAEs

    Measure: Frequency of AEs and SAEs

    Time: Day 14 visit from study initiation
    97 Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial

    CCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled trial, which aims to assess the safety and efficacy of treatment with convalescent plasma for patients with moderate-severe COVID-19. Participants will be randomized 2:1 to two parallel treatment arms: Convalescent plasma, and intravenous placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.

    NCT04345289
    Conditions
    1. COVID
    2. Corona Virus Infection
    3. Viral Pneumonia
    Interventions
    1. Biological: Convalescent anti-SARS-CoV-2 plasma
    2. Other: Infusion placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite outcome

    Measure: All-cause mortality or need of invasive mechanical ventilation

    Time: 28 days

    Secondary Outcomes

    Description: Number of participants with adverse events with possible relation to study drug

    Measure: Frequency of adverse events

    Time: 90 days

    Description: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines

    Measure: Frequency of severe adverse events

    Time: 90 days

    Description: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities

    Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status

    Time: 90 days

    Description: Number of days without mechanical ventilation

    Measure: Ventilator-free days

    Time: 28 days

    Description: Number of days without organ-failure

    Measure: Organ failure-free days

    Time: 28 days

    Description: Number of days in ICU

    Measure: Duration of ICU stay

    Time: 90 days

    Description: Number of deaths by any cause

    Measure: Mortality rate

    Time: 7, 14, 21, 28 and 90 days

    Description: Days from the date of hospital admission for COVID-19 to the date of discharge

    Measure: Length of hospital stay

    Time: 90 days

    Description: Days requiring supplement oxygen

    Measure: Duration of supplemental oxygen

    Time: 90 days
    98 A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia (CARDEA)

    Part 1 of this trial enrolled 30 patients to receive Auxora (formerly CM4620) in a 2:1 randomized, open label trial of patients with severe and critical COVID-19 pneumonia. Part 2 will consist of a randomized, double blind, placebo-controlled (RCT) study that will evaluate efficacy, safety, and the pharmacokinetic profile of Auxora in patients with severe COVID-19 pneumonia. Four hundred patients will be randomized 1:1 to receive Auxora or matching placebo. Patients with an estimated PaO2/FiO2 of 101-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. Subgroup analyses will be performed to explore how time to recovery is influenced by baseline variables and to evaluate the treatment effect at different levels of each of these variables. The dose of Auxora will be 2.0 mg/kg (1.25 mL/kg) administered at 0 hour, and then 1.6 mg/kg (1 mL/kg) at 24 hours and 1.6 mg/kg (1 mL/kg) at 48 hours from the SFISD. The dose of placebo will be 1.25 mL/kg administered at 0 hour and then 1 mL/kg at 24 hours and 1 mL/kg at 48 hours from the SFISD. Both remdesivir and corticosteroids will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides informed consent.

    NCT04345614
    Conditions
    1. Pneumonia
    Interventions
    1. Drug: Auxora
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as the number of days hospitalized but not requiring supplemental oxygen or ongoing medical care, or; discharged and requiring supplemental oxygen, or; discharged, not requiring supplemental oxygen.

    Measure: Number of days from the Start of the First Infusion of Study Drug (SFISD) to recovery

    Time: From start of first infusion of study drug to day 30

    Secondary Outcomes

    Measure: Proportion of patients requiring invasive mechanical ventilation or dying

    Time: from start of start of first infusion of study drug and up to day 30

    Measure: Proportion of patients requiring invasive mechanical ventilation

    Time: from start of start of first infusion of study drug and up to day 30

    Description: The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen

    Measure: Differences in outcomes as measured by an 8-point ordinal scale

    Time: from randomization through Days 12 and 30

    Measure: Proportion of patients who have died at day 30 (mortality)

    Time: Day 30

    Measure: Number of days in the hospital

    Time: from admission into the hospital until discharge from the hospital

    Measure: Number of days in the Intensive Care Unit (ICU)

    Time: from admission into ICU until discharge from ICU

    Measure: Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE)

    Time: from randomization and through day 30

    Description: Concentration measured using a validated assay

    Measure: CM4620-IE serum concentration

    Time: enrollment through 72 hours
    99 Randomized Trial Assessing Efficacy and Safety of Hydroxychloroquine Plus Azithromycin Versus Hydroxychloroquine for Hospitalized Adults With COVID-19 Pneumonia

    Double blinded randomized clinical trial designed to evaluate the efficacy and safety of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with confirmed COVID-19 pneumonia.

    NCT04345861
    Conditions
    1. Coronavirus Infection
    2. Pneumonia, Viral
    Interventions
    1. Drug: Hydroxychloroquine + placebo
    2. Drug: hydroxychloroquine + azithromycin
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points (score range from 1 to 7 , with 7 being the worst score)

    Measure: Time to clinical improvement of at least 1 level on the ordinal scale between Day 1 (day of the first administration of study drug) to Day 11 (day after last day of treatment).

    Time: up to Day 11

    Secondary Outcomes

    Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points at day 15 and day 29

    Measure: Clinical status assessed by ordinal scale

    Time: up to Day 29

    Description: Necessity for transfer to Intensive care unit

    Measure: transfer to ICU

    Time: up to Day 29

    Description: days from admission to hospital discharge

    Measure: Length of hospital day

    Time: up to Day 29

    Description: incidence of all-cause mortality

    Measure: Hospital Mortality

    Time: Day 29

    Description: Need to mechanical ventilation

    Measure: Need to Mechanical Ventilation

    Time: up to Day 29

    Description: adverse reactions

    Measure: Occurence of grade 3-4 adverse event

    Time: up to Day 29

    Description: ECG

    Measure: QTc Lengthening

    Time: up to Day 11

    Description: Thoracic CT scan : number and size of ground-glass opacifications on day 1 and day 11 Two independent pulmonary imagery experts will assess abnormalities according to a standardized framework

    Measure: Evolution of pulmonary CT scan images

    Time: up to Day 11
    100 Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Hydroxychloroquine Together With Baricitinib, Imatinib or Early Lopinavir / Ritonavir in Patients With SARS Cov2 Pneumonia

    In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak. For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases. The study aims to compare lopinavir / ritonavir (200 /50), imatinib 400mg, baricitinib 4mg, in combination with hydroxychloroquine 200mg, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment. Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1

    NCT04346147
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Hidroxicloroquine
    2. Drug: Lopinavir/ritonavir
    3. Drug: Imatinib tablets
    4. Drug: Baricitinib Oral Tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: time from inclusion to improvement by 2 points on the "seven-category ordinal scale" or high, whichever comes first

    Measure: time to clinical improvement

    Time: baseline to day 14

    Secondary Outcomes

    Description: number of serious adverse effects and premature discontinuation of treatment

    Measure: Safety of treatments

    Time: through study completion, an average of 1 month

    Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

    Measure: Tolerability of treatments

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

    Other Outcomes

    Description: Possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 using high-performance techniques with serum DNA from the participants

    Measure: Biomarkers and genetic markers of susceptibility to SARS-CoV-2

    Time: baseline
    101 An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

    The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.

    NCT04346355
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours

    Measure: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation

    Time: two weeks from participants' allocation to study arm

    Secondary Outcomes

    Description: Death

    Measure: Death from any cause

    Time: Two weeks from participants' allocation to study arm

    Description: Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale

    Measure: Tocilizumab toxicity

    Time: Two weeks from participants' allocation to study arm

    Description: Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment

    Measure: Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment

    Time: Two weeks from participants' allocation to study arm

    Description: Changes from baseline of the PaO2 / FiO2 ratio

    Measure: Evaluate the progress of the PaO2 / FiO2 ratio

    Time: Two weeks from participants' allocation to study arm

    Description: Changes from baseline of the lymphocyte count

    Measure: Evaluate the trend over time of the lymphocyte count

    Time: Two weeks from participants' allocation to study arm
    102 A Pilot Study to Explore the Efficacy and Safety of Rescue Theraphy With Antibodies From Convalescent Patients Obtained With Double -Filtration Plasmapheresis (DFPP) and Infused in Critically Ill Ventilated Patients With Coronavirus Disease 2019 (COVID-19)

    The 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID 19), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite any attempted treatment.. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Plasma-exchange is expensive and requires large volumes of substitution fluid. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The aforementioned limitations of plasma therapy can be overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP).DFPP is a modality of plasma purification that performs an initial plasma separation from blood, and the subsequent separation of specific molecules, on the basis of their specific molecular weight (cut-off), by using a fractionation filter. The Fractionation Filter 2A20, because of its membrane sieving cut-off, retains larger molecules and returns plasma along with smaller molecules to the circulation, including the major part of the albumin. The selection of the membrane 2A20 is related to the appropriate Sieving Coefficient for IgG that allows to efficiently collect antibodies from patients which are recovered from COVID-19, with negligible fluid losses and limited removal of albumin. The total amount of antibodies obtained during one DFPP session exceeds by three to four times the total amount provided to recipients with one unit of plasma obtained during one plasma-exchange session from one COVID-19 convalescent donor. This should result in more effective viral inhibition and larger benefit for the patient achieved with one unit of enriched immunoglobulin solution obtained with DFPP than with one unit of plasma obtained with plasma exchange. These observations provide the background for a pilot study aimed to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for critically ill patients with severe coronavirus (COVID-19) pneumonia requiring mechanical ventilation.

    NCT04346589
    Conditions
    1. Pneumonia, Ventilator-Associated
    2. Coronavirus Infection
    Interventions
    1. Biological: Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients
    MeSH:Pneumonia, Ventilator-Associated Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of mechanical ventilation days.

    Time: Through study completion, an average of 6 months.

    Secondary Outcomes

    Measure: Survival

    Time: Through study completion, an average of 6 months.

    Measure: Shift to Continuous Positive Airway Pressure (CPAP) ventilation

    Time: Through study completion, an average of 6 months.

    Measure: Referral to a sub-intensive care unit or discharge

    Time: Through study completion, an average of 6 months.

    Measure: Viral titer

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Measure: Anti COVID 19 IgG antibodies

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Measure: Anti COVID 19 IgM antibodies

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Description: Marker of complement activation in plasma.

    Measure: C5a concentration

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Description: Marker of complement activation in plasma.

    Measure: C3a concentration

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum C5b-9 concentration

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
    103 An Open Randomized Study of the Effectiveness of the Drug Dalargin for the Prevention and Treatment of Symptoms of Pulmonary Complications in Patients With Coronavirus Infection (SARS-COVID-19)

    The purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019 ). Test drug that will be administered to patients are: - Dalargin, solution for inhalation administration, - Dalargin, solution for intravenous and intramuscular administration.

    NCT04346693
    Conditions
    1. Acute Respiratory Tract Infection
    2. Acute Respiratory Insufficiency
    3. Pneumonia
    4. Septic Shock
    5. Hypoxemia
    Interventions
    1. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation.
    2. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection
    3. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation
    4. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation
    MeSH:Infection Respiratory Tract Infections Pneumonia Respiratory Insufficiency Pulmonary Valve Insufficiency Hypoxia
    HPO:Hypoxemia Pneumonia Pulmonary insufficiency Respiratory tract infection

    Primary Outcomes

    Description: Estimated by Polymerase chain reaction (PCR)

    Measure: The change of viral load in patients with SARS-COVID-19.

    Time: Upon patient inclusion in the study, after 96 hours and on the 10day;

    Description: Assessed through the entire patient participation in the study

    Measure: The frequency of development of Acute Respiratory Distress Syndrome (ADRS)

    Time: up to 10 days

    Description: The number of days a patient is hospitalized

    Measure: Duration of hospitalization

    Time: up to 10 days

    Description: Early mortality from all causes will be estimated

    Measure: The frequency of early mortality

    Time: up to 30 days

    Description: Late mortality from all causes will be estimated

    Measure: The frequency of late mortality

    Time: up to 90 days

    Description: Clinical status at the time of completion of participation in the study will be estimated based upon the following criteria: Death; Hospitalization is extended, on invasive mechanical ventilation of the lungs with extracorporeal membrane oxygenation; Hospitalization extended, on non-invasive ventilation; Hospitalization is extended, needs additional oxygen; Hospitalization is extended, additional oxygen is not required; Discharged.

    Measure: Clinical status at the time of completion of participation in the study

    Time: an average of 10 days
    104 An Open Randomized Study of the Effectiveness of the Drug Mefloquine, Tablets 250 mg, Produced by FSUE SPC "Farmzashita" of the Federal Medical Biological Agency, FMBA of Russia (Russia) for the Treatment of Patients With COVID19

    Study of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" Farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.

    NCT04347031
    Conditions
    1. Pneumonia, Viral
    2. Respiratory Failure
    Interventions
    1. Drug: Mefloquine
    2. Drug: Hydroxychloroquine
    3. Combination Product: Mefloquine + azithromycin + / - tocilizumab
    4. Combination Product: Hydroxychloroquine + azithromycin + / - tocilizumab
    MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The number of patients with development of respiratory failure requiring transfer to the ICU.

    Measure: 1st primary endpoint for group 1

    Time: up to 10 days

    Description: The period of clinical recovery.

    Measure: 2nd primary endpoint for group 1

    Time: up to 10 days

    Description: The period of clinical recovery.

    Measure: 1st primary endpoint for group 2

    Time: up to 10 days

    Description: Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)

    Measure: 2nd primary endpoint for group 2

    Time: through study completion, an average of 3 months

    Secondary Outcomes

    Description: A change in viral load by conducting PCR assay through different timeframes

    Measure: 1st secondary endpoint for group 1

    Time: on days 5 and 10

    Description: Frequency of clinical cure on day 10 from the start of therapy

    Measure: 2nd secondary endpoint for group 1

    Time: on day 10

    Description: The retention time of the reaction temperature from the start of the treatment.

    Measure: 3d secondary endpoint for group 1

    Time: up to 10 days

    Description: Concentration of C-reactive protein in blood plasma.

    Measure: 4th secondary endpoint for group 1

    Time: up to 10 days

    Description: Respiratory index.

    Measure: 5th secondary endpoint for group 1

    Time: up to 10 days

    Description: Frequency appearance unwanted phenomena and serious unwanted phenomena

    Measure: 6th secondary endpoint for group 1

    Time: up to 10 days

    Description: A change in viral load by conducting PCR assay through different timeframes

    Measure: 1st secondary endpoint for group 2

    Time: on days 5 and 10

    Description: Respiratory index.

    Measure: 2nd secondary endpoint for group 2

    Time: up to 10 days

    Description: The retention time of the reaction temperature from the start of treatment.

    Measure: 3d secondary endpoint for group 2

    Time: up to 10 days

    Description: Concentration of C-reactive protein in blood plasma.

    Measure: 4th secondary endpoint for group 2

    Time: up to 10 days

    Description: Number of patients required transition to alternative therapy schedule

    Measure: 5th secondary endpoint for group 2

    Time: up to 10 days

    Description: Frequency of adverse events and serious adverse events

    Measure: 6th secondary endpoint for group 2

    Time: up to 10 days
    105 EVALUATION OF THE EFFICACY OF THE HYDROXYCHLOROQUINE-AZITHROMYCIN COMBINATION IN THE IN THE PREVENTION OF COVID-19 RELATED SDRA

    Since end of December, a new coronavirus, close to the 2002 SARS coronavirus, cause serious pneumonias throughout world. There is currently no strong evidence of an efficient specific treatment. Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients. This study wants to evaluate the clinical impact of adding Azithromycin to Hydroxychloroquine in the treatment of Sars-CoV-2 pneumonia

    NCT04347512
    Conditions
    1. Sars-CoV-2, Community-Acquired Pneumonia,COVID-19
    Interventions
    1. Drug: Hydroxychloroquine and azithromycin treatment arm.
    2. Drug: Hydroxychloroquine
    3. Drug: Control arm
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A significant hypoxemia is an arterial partial pressure of oxygen of less than 60 mmHg despite an oxygen flow of more than 6 L/min, patient at rest.

    Measure: Rate of patients reaching a significant hypoxemia, in each arms.

    Time: From day 0 to day 7
    106 How COVID-19 Virus Outbreak Affects Antimicrobial Resistance in a Low-middle-income Country's ICU?

    A previous study showed a high incidence of ventilator-associated pneumonia to multidrug resistant pathogens in our ICU. That has been related to lack of compliance to hand hygiene among health care providers in ou ICU.

    NCT04348227
    Conditions
    1. Ventilator Associated Pneumonia
    Interventions
    1. Behavioral: Enhanced hygiene measures
    MeSH:Pneumonia, Ventilator-Associated Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Incidence of MDR bacteria in endotracheal aspirates

    Measure: MDR pathogens in endotracheal aspirates

    Time: 1 year

    Secondary Outcomes

    Description: Incidence of microorganisms in endotracheal aspirates

    Measure: Microorganisms in endotracheal aspirates

    Time: 1 year
    107 Observational Study on the Use of Canakinumab Administered Subcutaneously in the Treatment of Patients With COVID-19 Pneumonia

    The study is configured as a retrospective and prospective observational study. The study will be multi-center and will involve all COVID-19 pneumonia patients treated with canakinumab administered subcutaneously.

    NCT04348448
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Canakinumab 150 MG/ML [Ilaris]
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: percentage of patients treated with canakinumab sc who do not require intensive care treatment during hospitalization for COVID-19

    Measure: intensive care treatment

    Time: 9 months

    Secondary Outcomes

    Description: ICU stay times

    Measure: ICU stay times

    Time: 9 months

    Description: percentage of patients who died 1 month after treatment

    Measure: % died after 1 month after treatment

    Time: 9 months

    Description: time of hospitalization

    Measure: hospitalization

    Time: 9 months

    Description: number of adverse event

    Measure: adverse event

    Time: 9 months
    108 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 Sy 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
    109 A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia

    The primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care can alleviate the immune-mediated cytokine release syndrome (CRS) and reduce the time to recovery in hospitalized subjects with severe or critical COVID-19 pneumonia.

    NCT04351152
    Conditions
    1. Coronavirus Disease 2019 (COVID-19) Pneumonia
    Interventions
    1. Biological: Lenzilumab
    2. Drug: Standard of Care
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to recovery is defined as the first day on which a subject satisfies one of the following 3 categories from the 8-point ordinal scale (Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities).

    Measure: Time to Recovery

    Time: Up to 28 days

    Secondary Outcomes

    Measure: Incidence of Invasive Mechanical Ventilation and/or Death

    Time: Up to 28 days

    Measure: Incidence of severe acute respiratory distress syndrome (ARDS)

    Time: Up to 28 days

    Measure: Duration of Intensive Care Unit (ICU) Stay

    Time: Up to 28 days

    Measure: Ventilator-free Days

    Time: Up to 60 days

    Measure: Duration of Hospitalization

    Time: Up to 28 days

    Measure: Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale

    Time: Up to Day 28

    Measure: Time to Death

    Time: Up to Day 28

    Measure: Number of Subjects Alive and Off Oxygen

    Time: Up to 60 days

    Description: Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measure: Percentage of Participants Experiencing Adverse Events

    Time: Up to 60 days

    Description: Using the NCI CTCAE version 5.0

    Measure: Percentage of Participants Experiencing Serious Adverse Events

    Time: Up to 60 days

    Measure: Proportion of Subjects Discharged from Hospital

    Time: Up to Day 60

    Measure: All-cause Mortality and Proportion of Subjects Alive

    Time: Day 28 and Day 60

    Measure: Time to improvement in oxygenation for > 48 hours

    Time: Up to Day 28

    Measure: Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)

    Time: Up to Day 28

    Description: NEWS2 consists of: Physiological Parameters: respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), use of air or oxygen, systolic blood pressure (mmHg), pulse (per minute), consciousness and temperature (°C)

    Measure: Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours

    Time: Up to Day 28

    Measure: Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale

    Time: Up to Day 28

    Measure: Duration of Time on Low-flow or High-flow Supplemental Oxygen

    Time: Up to Day 28
    110 IV Infusion of Autologous Adipose Derived Mesenchymal Cells for Abatement of Respiratory Compromise in SARS-CoV-2 Pandemic (COVID-19)

    The aim of this study is to evaluate the safety and efficacy of autologous adipose-derived mesenchymal cells for treating confirmed or suspected patients with SARS-CoV-2 and compromised respiratory function requiring hospitalization. The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV to eligible patients will improve clinical outcomes of COVID 19 positive patients with severe pneumonia or ARDS by reducing or avoiding cytokine storm.

    NCT04352803
    Conditions
    1. Covid-19 Pneumonia
    2. Cyotokine Storm
    Interventions
    1. Biological: Autologous Adipose MSC's
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Incidence of unexpected adverse events within 28 days following IV administration of MSCs.

    Measure: Safety - Incidence of unexpected adverse events

    Time: up to 28 days

    Description: Changes in progression or rate of subjects progressing to mechanical ventilation

    Measure: Efficacy - Frequency of progression to mechanical ventilation

    Time: up to 28 days

    Description: Changes in time subjects remain on mechanical ventilation

    Measure: Efficacy - Changes in length of mechanical ventilation

    Time: up to 28 days

    Description: Changes in length of time subjects wean off of mechanical ventilation

    Measure: Efficacy - Changes in length of weaning of mechanical ventilation

    Time: up to 28 days

    Description: Length of Hospital Stay

    Measure: Efficacy - Changes in length of hospital stay

    Time: up to 28 days

    Description: Mortality rate from all causes

    Measure: Efficacy - Changes in mortality rate

    Time: up to 28 days
    111 A Prospective International Lung UltraSound Analysis (ILUSA) Study in Tertiary Maternity Wards During the SARS-CoV-2 Pandemic

    Currently there is a great need for an accurately and rapid assessment of patients suspected for Covid-19. Like CT, Lung Ultrasound (LUS) examination can potentially help with the initial triage of patients but also help track the evolution of the disease. LUS can be used in every setting, including settings with limited infrastructure, allowing the reduction of disparities in trials participation. LUS is also a practical approach that can be used by obstetricians/gynecologists, who are the primary care givers in the labour and delivery room. The International Lung UltraSound Analysis (ILUSA) Study is an international multicenter prospective explorative observational study to assess the predictive value of LUS in Covid-19 suspected and diagnosed pregnant patients.

    NCT04353141
    Conditions
    1. COVID
    2. Pregnancy Complications, Infectious
    3. Pregnancy Related
    4. Pregnancy, High Risk
    5. Pregnancy Disease
    6. Pneumonia
    7. Pneumonia, Viral
    8. Diagnoses Disease
    Interventions
    1. Diagnostic Test: standardized Lung Ultrasound (LUS) examination
    MeSH:Pregnancy Complications, Infectious Pneumonia, Viral Pneumonia Pregnancy Complications
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is diagnostic performance in terms of the area under the receiver operating characteristic curve (AUC, also known as the c-statistic) and sensitivity and specificity with regard to the prediction of poor outcome. Outcome at one week from admission: good outcome includes discharge or inpatient breathing in free air; poor outcome includes patient with oxygen support, patients with CPAP/ high oxygen flow cannula, or patient with endotracheal intubation during the week.

    Measure: Diagnostic performance of LUS to predict poor outcome

    Time: outcome one week after enrollment into the study
    112 Study of Biomarkers in the Long-term Impact of Coronavirus Infection in the Cardiorespiratory System: Effect of Hydroxychloroquine / Azithromycin Combined Therapy

    Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.

    NCT04353245
    Conditions
    1. COVID19
    2. Corona Virus Infection
    3. Myocardial Injury
    4. Pneumonia
    Interventions
    1. Other: BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM
    MeSH:Infection Communicable Diseases Coronavirus Infections Virus Diseases Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry

    Measure: Fibrosis

    Time: 12 months

    Description: Decreased functional capacity on ergospirometers

    Measure: Ergospirometers

    Time: 12 monthes
    113 Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia

    In the current situation it is of great importance to discover a safe, cost-effective and available treatment strategy in order to limit the rapidly spreading SARS-Cov-2. Recent studies have shown that hydroxychloroquine could have a role in the treatment of infected patients. It is however not very likely that hydroxychloroquine alone could be adequate for treatment of Covid-19 disease. Effective therapy that prevents the virus entrance should contain at least TMPRSS2 inhibitor or a competitive inhibitor of viral ACE 2 binding. The use of bromhexine at the dose adequate to selectively inhibit the TMPRSS2, resulting in preventing of viral entrance via TMPRSS2-specific pathway, coud be an effective treatment of Covid-19. In our study we would like to explore the therapeutic potential of bromhexin and hydroxychloroquine in Covid-19 patients. Hypothesis 1. Combined treatment with bromhexin and hydroxychloroquine shortens the course of disease in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 2. Combined treatment with bromhexin and hydroxychloroquine lowers the incidence of secundary pulmonary infections in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 3. Combined treatment with bromhexin and hydroxychloroquine decreases the need for ICU admission in hospitalized Covid-19 patients compared to hydroxychloroquine alone.

    NCT04355026
    Conditions
    1. Covid-19
    Interventions
    1. Drug: Bromhexine Oral Tablet and/or hydroxychloroquine tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: number of days the patient is treated in the hospital

    Measure: Duration of hospitalization

    Time: through study completion, an average of 6 months

    Description: Number of days from the onset of symptoms to hospital discharge

    Measure: Duration of disease

    Time: through study completion, an average of 6 months

    Secondary Outcomes

    Description: Incidence of HAP

    Measure: Hospital-aquired pneumonia

    Time: through study completion, an average of 6 months

    Description: Number of days spent in the ICU

    Measure: ICU stay duration

    Time: through study completion, an average of 6 months

    Description: number of days on oxygene therapy

    Measure: Oxygene therapy duration

    Time: through study completion, an average of 6 months

    Description: Number of hours on mechanical ventilation

    Measure: Mechanical ventilatory support duration

    Time: through study completion, an average of 6 months
    114 Efficacy of Captopril Nebulization in Covid-19 Patients Suffering of SARS CoV-2 Pneumonia. A Randomized Phase II Study

    Captopril being an effective drug available in liquid preparation, administration by nebulization could be of interest for maximizing lung action and minimizing systemic side effects. Such a treatment might be used for "Covid-19" patients with pneumonia in order to avoid ARDS.

    NCT04355429
    Conditions
    1. Pneumonia
    2. Coronavirus Infection
    3. COVID-19
    Interventions
    1. Drug: captopril 25mg
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To assess determine the efficacy of captopril nebulization addition to standard of care compared to standard of care in term of 14-day ventilation free survival

    Measure: Efficacy of captopril nebulization addition to standard of care compared to standard of care.

    Time: 14 Days
    115 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

    116 Treatment With Inhaled Corticosteroids in Patients Hospitalized Because of COVID19 Pneumonia

    Randomized, prospective, controlled open label clinical trial aimed at investigating if the addition of inhaled corticosteroids (budesonide) reduces treatment failure (defined as a composite variable by the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) according to hospital standard of care guidance) at day 15 after initiation of therapeutic intervention.

    NCT04355637
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Inhaled budesonide
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: composite variable that includes the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) at day 15 after initiation of therapeutic intervention

    Measure: Proportion of patients in both arms fulfilling the criteria for treatment failure

    Time: 15 days after treatment

    Secondary Outcomes

    Description: Yes/no

    Measure: ICU admission

    Time: baseline, day 3, day 7, day 15, day 30

    Description: yes/no and reason

    Measure: ICU refusal

    Time: baseline, day3, day 7, day 15, day 30

    Description: infectious cardiovascular and /or metabolic complications as well as variation in the 7 point WHO scale.

    Measure: Occurrence of complications

    Time: baseline, day3, day 7, day 15, day 30

    Description: U/L

    Measure: lactate dehydrogenase (LDH)

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: mg/dL

    Measure: C Reactive Protein (CRP)

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: ng/mL

    Measure: ferritin

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: ng/mL

    Measure: D-dimer

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: x10^9/L

    Measure: leukocyte counts

    Time: at baseline, day 3, day 7, day 15, day 30
    117 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. Ventilatory Failure
    3. COVID-19
    4. Pneumonia
    5. 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
    118 COVID-19: A Pilot Study of Adaptive Immunity and Anti-PD1

    This is an open-label, controlled, single-centre pilot study of nivolumab in adult patients with COVID-19. This clinical study aims to evaluate efficacy of anti-PD1 antibody in relation to viral clearance and its safety.

    NCT04356508
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    3. 2019-nCoV
    4. Pneumonia, Viral
    Interventions
    1. Drug: Nivolumab
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Viral load changes in NPS based on SARS-CoV-2 RT-PCR

    Measure: Viral clearance kinetics

    Time: From diagnosis to recovery, assessed up to 6 months

    Secondary Outcomes

    Description: Incidence and severity of treatment-related adverse events

    Measure: Treatment-related adverse events of nivolumab (Intervention arm only)

    Time: Up to 1 year after nivolumab dosing

    Description: Changes in lymphocyte counts

    Measure: Lymphocyte kinetics

    Time: On days 1, 4, 6, 8, 10 and 28 from study enrollment

    Description: Changes in cytokine levels (e.g. IL-1B, IL-2, IL-6, TNFa)

    Measure: Cytokine kinetics

    Time: On days 1, 4, 6, 8 and 10 from study enrollment

    Measure: Length of inpatient stay due to COVID-19

    Time: From hospital admission to discharge, assessed up to 6 months
    119 Efficacy of Pulmonary Physiotherapy on Hospitalized Patients With Novel Coronavirus 2019 Pneumonia

    The aim of this study is to evaluate the efficacy of pulmonary physiotherapy on respiratory functions in hospitalized patients with Novel Coronavirus 2019 pneumonia. Patients will be randomized into 1) intervention group: receiving pulmonary physiotherapy technique to improve pulmonary function and walking training or 2) control group: Usual medical care. Patients in both groups will receive therapeutic incentive spirometer. Various outcome measurements of pulmonary functions will be evaluated before and after of interventions. Mortality rate, hospitalization duration and re-admission will be followed until one month after end of intervention. Also, patient's quality of life will be measured after one month.

    NCT04357340
    Conditions
    1. Covid-19
    2. Pneumonia
    3. SARS Pneumonia
    Interventions
    1. Other: Pulmonary Physiotherapy Techniques
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Partial pressure of oxygen in mixed venous blood.

    Measure: Mixed venous O2 pressure (PVO2)

    Time: Baseline

    Description: Partial pressure of oxygen in mixed venous blood.

    Measure: Mixed venous O2 pressure (PVO2)

    Time: Day 3

    Description: Partial pressure of carbon dioxide in mixed venous blood.

    Measure: Mixed venous CO2 pressure (PVCO2)

    Time: Baseline

    Description: Partial pressure of carbon dioxide in mixed venous blood.

    Measure: Mixed venous CO2 pressure (PVCO2)

    Time: Day 3

    Description: Measure of the venous blood acidity or alkalinity

    Measure: PH

    Time: Baseline

    Description: Measure of the venous blood acidity or alkalinity

    Measure: PH

    Time: Day 3

    Description: The amount of bicarbonate ion in the venous blood

    Measure: HCO3

    Time: Baseline

    Description: The amount of bicarbonate ion in the venous blood

    Measure: HCO3

    Time: Day 3

    Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood

    Measure: Oxygen saturation (O2 Sat) from VBG

    Time: Baseline

    Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood

    Measure: Oxygen saturation (O2 Sat) from VBG

    Time: Day 3

    Description: The distance a patient can walk during three minute

    Measure: Three minute walk test

    Time: Baseline

    Description: The distance a patient can walk during three minute

    Measure: Three minute walk test

    Time: Day 3

    Measure: O2 Sat after one minute walking

    Time: Baseline

    Measure: O2 Sat after one minute walking

    Time: Day 3

    Measure: O2 Sat after two minutes use of Partial Rebreather

    Time: Baseline

    Measure: O2 Sat after two minutes use of Partial Rebreather

    Time: Day 3

    Measure: O2 Sat after two minutes free air breathing

    Time: Baseline

    Measure: O2 Sat after two minutes free air breathing

    Time: Day 3

    Measure: O2 sat/ Fio2

    Time: Baseline

    Measure: O2 sat/ Fio2

    Time: Day 3

    Secondary Outcomes

    Description: The number of dead subjects compared to total patients

    Measure: Mortality rate

    Time: until one month

    Description: Patients' hospitalization after discharge due to any reason

    Measure: Number of participants with Rehospitalization

    Time: until one moth

    Description: Using Short-form 36 questionnaire. The minimum score is 0 and the maximum score is 100. Higher scores mean patient's better quality of life.

    Measure: The Health-Related Quality of Life (HRQOL)

    Time: One month after end of intervention

    Description: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.

    Measure: breathlessness

    Time: Baseline

    Description: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.

    Measure: breathlessness

    Time: Day 3
    120 Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium

    The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

    NCT04357457
    Conditions
    1. Covid 19
    2. Hypoxemic Respiratory Failure
    Interventions
    1. Drug: Almitrine
    2. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

    Measure: Rate of endotracheal intubation

    Time: 7 days

    Secondary Outcomes

    Measure: 28-day mortality

    Time: 28 days

    Measure: In-hospital mortality

    Time: 28-day

    Measure: Number of ventilator-free days

    Time: 28 days

    Measure: Number of days in the ICU

    Time: 28 days

    Measure: Number of days in the hospital

    Time: 28 days

    Description: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.

    Measure: Discontinuation rate of the treatment

    Time: 28 days
    121 COVID-19 Epidemic Response Study: A National Observational Longitudinal Non-Interventional Protocol

    A national, observational, longitudinal, non-interventional program aiming to identify prognostic parameters, to investigate the kinetics of the immune response, and to identify predictive biomarkers in SARS-CoV-2 infected patients.

    NCT04357496
    Conditions
    1. Fever
    2. Pneumonia
    3. Cough
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Blood samples drawn from the infected participants will be analysed for prognostic parameters.

    Measure: Identification of prognostic parameters for SARS-CoV-2 infected participants.

    Time: 7 months

    Secondary Outcomes

    Description: Systems from Abbott and Euroimmun will be used for IgG and IgM in SARS-CoV-2.

    Measure: Investigation of the kinetics of immune activation and antibody production against SARS-CoV-2 and correlation with clinical course

    Time: 7 months

    Other Outcomes

    Description: Genomic, proteomic, and transcriptomic analyses will be performed on the blood samples drawn from Covid-19 infected participants over the course of 6 months.

    Measure: Identification of predictive biomarker/s for clinical course in mildly and severely affected Covid-19 patients using genomic, proteomic, and transcriptomic approach.

    Time: 7 months
    122 A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia

    Study Objectives: Primary - To assess the efficacy (survival without organ failure on Day 14) of three doses of rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or 6 on the World Health Organization (WHO) 9-point severity scale - To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale Secondary - To further assess the efficacy of IV administered rhu-pGSN - To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN - To evaluate the effect of administered rhu-pGSN on survival rates - To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes - [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN Immunogenicity • To investigate the development of antibodies against rhu-pGSN post-treatment

    NCT04358406
    Conditions
    1. Sars-CoV2
    Interventions
    1. Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

    Measure: Efficacy: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

    Time: Day 14

    Description: Proportion of subjects with SAEs as judged by the investigator

    Measure: Safety and Tolerability: Proportion of subjects with serious adverse events (SAEs)

    Time: Continuous through Day 28

    Secondary Outcomes

    Description: Daily change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection

    Measure: Efficacy: Daily change in the WHO 9-point severity score

    Time: Daily through at least Day 14

    Description: All cause mortality rate using Kaplan-Meier survival analysis

    Measure: Efficacy: All cause mortality rate at Days 28 and 90

    Time: At Days 28 and 90

    Description: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit, new ongoing need for dialysis/renal replacement therapy

    Measure: Efficacy: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy

    Time: Days 7, 28, 60, and 90

    Description: Proportion of subjects discharged to home or immediate prior residence

    Measure: Efficacy: Proportion of subjects discharged to home or immediate prior residence

    Time: Continuous through Day 28

    Description: LOS of surviving subjects in the hospital and in ICU

    Measure: Efficacy: Length of stay (LOS) of surviving subjects in the hospital and in ICU

    Time: Continuous through day 28

    Description: Proportion of subjects readmitted to the hospital

    Measure: Efficacy: Proportion of subjects readmitted to the hospital

    Time: Up to 90 days

    Description: Proportion of subjects with adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measure: Safety and Tolerability: Proportion of subjects with adverse events (AEs)

    Time: Continuous through Day 28

    Description: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

    Measure: Safety and Tolerability: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

    Time: Continuous through Day 28

    Description: Proportion of subjects with rhu-pGSN antibodies

    Measure: Immunogenicity: Proportion of subjects with rhu-pGSN antibodies

    Time: Days 1, 28, and 90

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

    Measure: Pharmacokinetics: Maximum concentration (C max) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

    Measure: Pharmacokinetics: Time to maximum concentration (T max) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Half-life (T 1/2) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Area under the curve from time 0 to 8 hours (AUC 0-8) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Area under the curve from time 0 to infinity (AUC 0-inf) of added rhu-pGSN

    Time: Continuous through day 3
    123 Mortality Prediction Model for the Triage of COVID-19, Pneumonia and Mechanically Ventilated ICU Patients

    The objective of this study is to develop and evaluate an algorithm which accurately predicts mortality in COVID-19, pneumonia and mechanically ventilated ICU patients.

    NCT04358510
    Conditions
    1. COVID-19
    2. Pneumonia
    3. Mechanical Ventilation
    Interventions
    1. Device: COViage
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Deceased or not deceased

    Measure: Mortality outcome in COVID-19 ICU patients

    Time: Through study completion, an average of 2 months

    Description: Deceased or not deceased

    Measure: Mortality outcome in mechanically ventilated ICU patients

    Time: Through study completion, an average of 2 months

    Description: Deceased or not deceased

    Measure: Mortality outcome in pneumonia ICU patients

    Time: Through study completion, an average of 2 months
    124 Expanded Access: Pulsed, Inhaled Nitric Oxide (iNO) for the Treatment of Patients With Mild or Moderate Coronavirus Disease (COVID-19)

    The search for novel therapies to address the ongoing coronavirus (COVID-19) pandemic is ongoing. No proven therapies have been identified to prevent progression of the virus. Preliminary data suggest that inhaled nitric oxide (iNO) could have benefit in preventing viral progression and reducing reliance on supplemental oxygen and ventilator support. Expanded access allows for iNO to be delivered via the portable INOpulse delivery system for the treatment of COVID-19.

    NCT04358588
    Conditions
    1. Coronavirus Infection
    2. COVID-19
    3. Pneumonia, Viral
    Interventions
    1. Drug: iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    125 Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact

    Retrospective study on the efficacy of baricitinib in 12 COVID-19 patients with moderate pneumonia.

    NCT04358614
    Conditions
    1. COVID
    2. Pneumonia
    Interventions
    1. Drug: Baricitinib 4 MG Oral Tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: All adverse event recording

    Measure: To assess the safety of baricitinib combined with antiviral (lopinavir-ritonavir) in terms of serious or non-serious adverse events incidence rate.

    Time: 2 weeks

    Secondary Outcomes

    Description: The percentage of patients improving the clinical and respiratory parameters compared with controls.

    Measure: To evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters.

    Time: 2 weeks

    Description: The percentage of ICU admission in baricitinib group as compared with controls.

    Measure: ICU admission rate

    Time: 2 weeks

    Description: The percentage of discharged in baricitinib group as compared with controls.

    Measure: Discharge rate.

    Time: 2 weeks
    126 Anxiety and Work Resilience Among Tertiary University Hospital Workers During the COVID-19 Outbreak: An Online Survey

    For limiting COVID-19 spreading, the World Health Organisation (WHO) recommended worldwide confinement on 2010. In France, unessential institutions were closed on March 14th and population confinement was decided on March 17th. Quarantine and/or confinement could lead to psychological effects such as confusion, suicide ideation, post-traumatic stress symptoms or anger COVID-19 outbreak highlighted a considerable proportion of health care workers (HCW) with depression, insomnia, anxiety and distress symptoms. In front line, facing the virus with the fear of contracting it and contaminate their closest. During previous outbreaks (H1N1, SARS), HCWs have been shown to experience such negative psychological effects of confinement as well as work avoidance behaviour and physical interaction reduction with infected patients (4-7). In France, Covid 19 outbeak led to increase ICU bed capacity with a full reorganization of the human resources. Some caregivers were reassigned to newly setup units admitting or not Covid-19 patients. In the same time, non-caregivers were also encouraged to work at home whenever possible. Thus, every hospital staff member's private and professional life could be altered by the Covid-19 outbreak. As all these changes in the daily life could induce psychological disturbances, the present study was aimed at assessing the acute anxiety level (main objective) of the staff in our Tertiary University Hospital, (6300 employees). Secondarily, the self-reported insomnia, pain, catastrophism and work avoidance behaviour levels were assessed

    NCT04358640
    Conditions
    1. Critical Illness
    2. Sars-CoV2
    3. SARS Pneumonia
    4. Coronavirus Infection
    5. Stress Disorders, Post-Traumatic
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Critical Illness Stress Disorders, Post-Traumatic
    HPO:Pneumonia

    Primary Outcomes

    Description: Mesured by STAY Scale

    Measure: Anxiety

    Time: 15 to 45 days after the beginning of the outbreak

    Secondary Outcomes

    Description: Participant suffering of Insomnia

    Measure: Insomnia

    Time: 15 to 45 days after the beginning of the outbreak

    Description: Participant suffering of catastrophism

    Measure: Catastrophism

    Time: 15 to 45 days after the beginning of the outbreak
    127 Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Plasma From Patients Cured of COVID-19 Compared to the Best Available Therapy in Subjects With SARS-CoV-2 Pneumonia

    In early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.

    NCT04358783
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Biological: Plasma
    2. Other: Best Available Therapy
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: any cause mortality during the first 14 days of treatment

    Measure: Early all-cause mortality

    Time: 14 days

    Secondary Outcomes

    Description: (48-hour sampling interval from day 3 of hospitalization to two consecutive negatives).

    Measure: Time in days for SARS-CoV-2 RT-PCR negatives

    Time: 90 days

    Description: In subjects of both arms at day 0, 3, 7, 14 and 90.

    Measure: The serum anti-SARS-CoV-2 antibody titres

    Time: 90 days

    Description: Comparison of anti-SARS-CoV-2 antibody titers

    Measure: Detection of serum antibodies

    Time: days 0, 3, 7, 14 and 90.
    128 Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia in Grand Ouest Interregion France

    To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD). We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.

    NCT04359511
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Prednisone
    2. Drug: Hydrocortisone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The 7-category ordinal scale is as follow: Not hospitalized with resumption of usual activities Not hospitalized, but unable to resume usual activities Hospitalized, not requiring O2 Hospitalized, requiring O2 from 1 to 5 l/min Hospitalized, requiring O2 >6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death.

    Measure: Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.

    Time: 14 days

    Secondary Outcomes

    Measure: Proportion of patients free of oxygen at day 14 and 28

    Time: 14 and 28 days

    Measure: Proportion of patients discharged alive from hospital at day 14 and 28

    Time: 14 and 28 days

    Measure: Time to discharge for patients alive

    Time: 28 days

    Measure: Proportion of patients that were hospitalized to ICU or who died at day 14 and 28

    Time: 14 and 28 days

    Measure: 14 and 28 day mortality rate

    Time: 14 and 28 days

    Measure: The time until weaning from oxygen therapy

    Time: 28 days

    Measure: The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28

    Time: 14 and 28 days
    129 Prognostic Value of Serum Interleukin-6 (IL-6) and Soluble Interleukin-6 Receptor (sIL-6R) in Severe Coronavirus Disease (COVID-19) Pneumonia Treated With Tocilizumab - a Prospective Single Center Study (UHID-COVID19)

    This is a single arm, prospective, observational, single center study to assess the role of interleukin-6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) as predictors of efficacy and safety outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab. At least 30 patients will be enrolled who are diagnosed with severe COVID-19 pneumonia and meet the entry criteria.

    NCT04359667
    Conditions
    1. COVID-19
    2. Severe Pneumonia
    Interventions
    1. Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: baseline

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: 24 hours post treatment

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: 48 hours post treatment

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: on Day 7

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: on Day 28
    130 Bacterial and Fungal Microbiota of Patients With Severe Viral Pneumonia With SARS-CoV2

    Observational pilot single-center study aiming to determine the microbiota of critically ill patients infected with SARS-CoV-2. COVID-19 patients will be compared to historical critically ill controls with no SARS-CoV-2 infection.

    NCT04359706
    Conditions
    1. Sars-CoV2
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: relative abundances and diversity indices

    Measure: Composition of the fecal bacterial and fungal microbiota

    Time: At 28 days

    Secondary Outcomes

    Description: Alterations in fecal microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls

    Measure: Analysis of the faecal microbiota from rectal swab

    Time: at baseline and every 7 days during 28 days

    Description: Alterations in respiratory microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls

    Measure: Analysis of the respiratory microbiota from the bronchoalveolar lavage liquid

    Time: at baseline and every 7 days during 28 days

    Description: Changes in blood, c-reactive protein, leucocyte, lymphocyte from baseline

    Measure: Serum inflammatory markers changes

    Time: at 28 days,

    Description: changes in Cytokine/ chemokine from baseline

    Measure: Inflammatory markers changes

    Time: at 28 days,

    Description: death

    Measure: Mortality

    Time: at 28 days,

    Description: Number of days alive without mechanical ventilation

    Measure: mechanical ventilation free days

    Time: at 28 days,
    131 PEEP Incremental and Decremental Alveolar Recruitment of Critically Ill COVID-19 Patients Under Electric Impedance Tomography (EIT)

    COVID-19 originated from Severe Acut Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to critical condition due to hypoxemic respiratory failure with the background of viral pneumonia. Both alevolar recruitment and the subsequent optimal positive end-expiratory pressure (PEEP) adjustment has a pivotal role in the elimination of atelectasis developed by inflammation in the lung parenchyma The gold standard of the follow up of recruitment manoeuvre is the chest computed tomography (CT) examination. However, reduction of intrahospital transport and the exposure with healthcare workers are recommended because of the extremely virulent pathogen spreading easily by droplet infection. In this case bedside investigations have an utmost importance in the management of hygiene regulations. Electric impedance tomography (EIT) is a non-invasive, radiation free functional imaging technique easily applicable at the bedside.

    NCT04360837
    Conditions
    1. COVID-19
    2. Virus; Pneumonia
    3. Atelectasis
    Interventions
    1. Procedure: alveolar recruitment
    MeSH:Pneumonia, Viral Pneumonia Pulmonary Atelectasis
    HPO:Atelectasis Pneumonia

    Primary Outcomes

    Description: Estimation of change in compliance (ml/cmH2O) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.

    Measure: Changes in lung compliance

    Time: 20 minutes

    Description: Estimation of change in global impedance (%) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.

    Measure: Change in global impedance

    Time: 20 minutes

    Description: Estimation of change in global impedance (%) on a daily manner.

    Measure: Change in recruitability

    Time: 7 days

    Secondary Outcomes

    Description: Change in arterial partial pressure of oxygen (PaO2) (mmHg) following recruitment

    Measure: Gas exchange

    Time: 20 minutes and 7 days

    Description: Change in plateau pressure (cmH2O) following recruitment

    Measure: Plateau pressure

    Time: 20 minutes and 7 days

    Description: Change in end expiratory lung impedance (%)

    Measure: End expiratory lung impedance (EELI)

    Time: 20 minutes and 7 days

    Description: Change in antero-to-posterior ventilation ratio (%) following intervention

    Measure: Antero-to-posterior ventilation ratio

    Time: 20 minutes and 7 days

    Description: Change in center of ventilation (%) following intervention

    Measure: Center of ventilation

    Time: 20 minutes and 7 days

    Description: Change in global inhomogeneity index (%) following intervention

    Measure: Global inhomogeneity index

    Time: 20 minutes and 7 days
    132 Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial

    This trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.

    NCT04360876
    Conditions
    1. COVID-19
    2. ARDS
    Interventions
    1. Drug: Dexamethasone injection
    2. Drug: Placebos
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.

    Measure: Ventilator Free Days (VFD) at Day 28

    Time: 28 Days

    Secondary Outcomes

    Description: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.

    Measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.

    Time: 14 Days

    Measure: Clinical Status at day 28 as measured by WHO 7-point ordinal scale

    Time: 28 Days

    Measure: In-Hospital Mortality at day 28

    Time: 28 Days

    Measure: In-Hospital Mortality at day 90

    Time: 90 Days

    Measure: Time to Mortality to day 28

    Time: 28 Days

    Measure: ICU-free days to day 28

    Time: 28 Days

    Measure: Hospital Length of Stay among survivors to day 90

    Time: 90 Days

    Measure: Severity of ARDS to day 10

    Time: 10 Days

    Measure: Days to resolution of fever

    Time: 28 Days

    Measure: Change in C-Reactive Protein (CRP) level from baseline to day 10

    Time: 10 Days

    Measure: Vasopressor-free days to day 28

    Time: 28 Days

    Measure: Renal replacement-free days to day 28

    Time: 28 Days

    Measure: Duration of mechanical ventilation to day 28

    Time: 28 Days

    Measure: Oxygenation-free days to day 28

    Time: 28 Days

    Measure: Incidence of New Mechanical Ventilation to day 28

    Time: 28 Days

    Measure: Change in sequential organ failure assessment (SOFA) score from baseline to day 10

    Time: 10 Days

    Measure: In-hospital adverse events to day 28

    Time: 28 Days

    Measure: Discontinuation of study drug infusion

    Time: 10 Days
    133 Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)

    Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

    NCT04361942
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal Stromal Cells
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Index of therapy success to preserve Intensive Care Hospitalization space

    Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation

    Time: 0-7 days

    Description: To measure global success

    Measure: Rate of mortality

    Time: 28 days

    Secondary Outcomes

    Description: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2

    Measure: Proportion of patients who have achieved clinical response

    Time: 0-7days

    Description: Evaluation of pneumonia changes

    Measure: Proportion of patients who have achieved radiological responses

    Time: 0-28 days

    Other Outcomes

    Description: Haemogram and cell subpopulations

    Measure: Blood white cell counts and their subpopulations.

    Time: 0-180 days

    Description: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs

    Measure: Cellular markers of inflammation

    Time: 0-180 days

    Description: IL-10, IL-6, IP-10, TNF-alpha

    Measure: Cytokines and chemokines in peripheral blood

    Time: 0-180 days
    134 Clinical Features and Risk Factors Associated With Worse Outcome in Patients Hospitalized for Covid-19 Pneumonia in France

    The aim of the research is to improve patient management by rapidly identifying, based on the terrain and clinical and biological characteristics, those patients likely to present a severe form of ARDS at risk of leading to intensive care

    NCT04362345
    Conditions
    1. Covid-19
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Identification of risk factors for severity (death or transfer to resuscitation) of Covid-19 infection

    Time: Files analysed retrospectively from March 1st, 2020 to April 15, 2020 will be examined]
    135 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

    This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

    NCT04362813
    Conditions
    1. Pneumonia and Cytokine Release Syndrome (Covid-19)
    Interventions
    1. Drug: Canakinumab
    2. Drug: Placebo
    MeSH:Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.

    Measure: Number of patients with clinical response

    Time: Day 3 to Day 29

    Secondary Outcomes

    Description: COVID-19-related death during the 4-week period after study treatment.

    Measure: COVID-19-related death rate during the 4-week period after study treatment

    Time: 4 weeks

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the C-reactive protein (CRP)

    Time: Baseline, Day 29

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the serum ferritin

    Time: Baseline, Day 29

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the D-dimer

    Time: Baseline, Day 29

    Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).

    Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs

    Time: 127 days
    136 Azithromycin With Amoxicillin/Clavulanate Versus Amoxicillin/Clavulanate Alone in COVID-19 Patients With Pneumonia and Hospitalized in a Non-intensive Care Unit Ward (AziA): a Superiority Open-label Randomized Controlled Trial

    The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.1 As of April 14, 2020, there have been more than 1.5 million reported cases and 124 000 deaths in more than 200 countries. A recent open-label nonrandomized French study reporte that addition of azithromycin to hydroxychloroquine in 6 patients resulted in numerically superior viral clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%) or control (2/16, 12.5%). Azithromycin alone has never been tested, whereas azithromycin has immunomodulating and anti-inflammatory properties that could theoretically prevent or limit secondary worsening. Our hypothesis is that azithromycin combined with amoxicillin/clavulanate will be superior to amoxicillin/clavulanate alone to obtain viral clearance at Day 6 in COVID-19 patients with pneumonia and hospitalized in a non-intensive care unit ward.

    NCT04363060
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Combination Product: Azithromycin with amoxicillin/clavulanate
    2. Drug: amoxicillin/clavulanate
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

    Measure: Rate of positive SARS-CoV-2 RT-PCR

    Time: Day 6

    Secondary Outcomes

    Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

    Measure: Rate of positive SARS-CoV-2 RT-PCR

    Time: Day 10

    Description: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)

    Measure: Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19

    Time: day 6, day 10, and day 30

    Description: Total duration of antibiotic treatment during the 30 days following inclusion

    Measure: Total duration of antibiotic treatment during the 30 days following inclusion

    Time: 30 days

    Description: Number of all-cause mortality during the 30 days following inclusion

    Measure: Number of all-cause mortality during the 30 days following inclusion

    Time: 30 days

    Description: Number of in-hospital mortality during the 30 days following inclusion

    Measure: Number of in-hospital mortality during the 30 days following inclusion

    Time: 30 days

    Description: Number of patients transferred to intensive care unit during the 30-day follow-up

    Measure: Number of patients transferred to intensive care unit during the 30-day follow-up

    Time: 30 days

    Description: Number of days without mechanical ventilation during the 30 days following inclusion

    Measure: Number of days without mechanical ventilation during the 30 days following inclusion

    Time: 30 days

    Description: adverse events attributable to antibiotic treatment during the 30 days following inclusion

    Measure: adverse events attributable to antibiotic treatment during the 30 days following inclusion

    Time: 30 days

    Description: Hospital length of stay during the 30 days following inclusion

    Measure: Hospital length of stay during the 30 days following inclusion

    Time: 30 days
    137 Impact of Obstructive Sleep Apnea on Covid-19 Outcomes (OSACOVID-19 Study): A Prospective Observational Cohort Study

    Covid-19 infection is an on-going pandemic with worse diagnosis in adults with comorbid conditions such as hypertension and cardiopulmonary diseases. Obstructive sleep apnea (OSA) is common in those comorbidities and may contribute to worse prognosis for the Covid-19 cases.

    NCT04363333
    Conditions
    1. COVID
    2. Obstructive Sleep Apnea
    3. Pneumonia
    Interventions
    1. Diagnostic Test: Home Sleep Apnea Testing or In-hospital Polysomnography
    MeSH:Apnea Sleep Apnea Syndromes Pneumonia Sleep Apnea, Obstructive
    HPO:Apnea Obstructive sleep apnea Pneumonia Sleep apnea

    Primary Outcomes

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 7 days

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 14 days

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 21 days

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 28 days

    Secondary Outcomes

    Description: Time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality

    Measure: Clinical status - improvement

    Time: 7, 14, 21, 28 days

    Description: Defined as an increase in category on a 7-category ordinal scale from admission

    Measure: Clinical status - worsening

    Time: 7, 14, 21, 28 days

    Other Outcomes

    Description: Re-analysis of the correlation of obstructive sleep apnea (objectively verified) severity in terms of apnea-hypopnea index and oxygenation levels with the primary and secondary outcomes as described above (the rate of clinical improvement defined as a decline of 2 categories from admission on a 7-category ordinal scale; time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality as well as with the lung function, CO-diffusion capacity, cardiac function, CT thorax pathologies, biomarkers (cytokines, polymorphisms) and IgG-antibodies after 4 months.

    Measure: Long-term outcomes

    Time: 4-6 months after the initial hospital admission
    138 A Phase-II, Open-Label, Randomized, Multicenter Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of 8 mg/kg or 4mg/kg Intravenous Tocilizumab in Patients With Moderate to Severe COVID-19 Pneumonia

    This study will assess the pharmacodynamics, pharmacokinetics, safety and efficacy of two different doses of tocilizumab (TCZ) in combination with standard-of-care (SOC) in hospitalized adult participants with moderate to severe COVID-19 pneumonia.

    NCT04363736
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tociliuzumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Serum Concentration of interleukin-6 (IL-6) Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of Ferritin Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of C-reactive Protein (CRP) Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of IL-6 Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of sIL-6R Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of Ferritin Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of CRP Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Secondary Outcomes

    Measure: Pecentage of Participants with Adverse Events

    Time: Up to Day 28

    Measure: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time

    Time: Up to Day 28

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

    Time: Up to Day 28

    Measure: Proportion of Participants with any Post-Treatment Infection

    Time: Up to Day 28
    139 A Prospective, Open-label, Randomized Pilot Study (Including a Control Group) of BACTEK-R (MV130), Administered Sublingually to Assess the Clinical Impact in Subjects With Mild Pneumonia Due to COVID-19

    The purpose of the study is to confirm if BACTEK-R (MV130) provides clinical benefit in subject with mild pneumonia (CURB-65≤2) by COVID-19 admitted to the Hospital.

    NCT04363814
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Bactek-R
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of subjects presenting a improvement in their clinical condition from day 1 to 14 that lead their hospital discharged. Based on the measure of the secondary outcomes.

    Measure: Clinical recovery

    Time: 2 weeks

    Description: Number of subjects presenting a worsening in their clinical condition from day 1 to 14 that leads to their admission to the intensive care unit or their death. Based on the measure of the secondary outcomes.

    Measure: Clinical worsening

    Time: 2 weeks

    Secondary Outcomes

    Description: Symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) will be daily record and classified as mild, moderate, severe.

    Measure: Clinical severity

    Time: 2 weeks

    Description: Time of reduction or disappearance of the symptoms

    Measure: Time to symptoms remission

    Time: 2 weeks

    Description: Record of all the medication administered to the subject

    Measure: Medication Use

    Time: 2 weeks

    Description: Time from the subject's admission to the coronavirus unit until discharge

    Measure: Hospitalization time

    Time: 2 weeks

    Description: Blood routine test will be carried out days 1 and 7

    Measure: Blood routine test

    Time: Days 1 and 7

    Description: Heart rate will be followed everyday during time frame

    Measure: Heart rate

    Time: 2 weeks

    Description: Blood pressure will be followed everyday during time frame

    Measure: Blood pressure

    Time: 2 weeks

    Description: Cardiac auscultation will be recorded everyday during time frame

    Measure: Cardiac auscultation

    Time: 2 weeks

    Description: Blood oxygen saturation will be followed everyday during time frame

    Measure: Oxygen saturation

    Time: 2 weeks

    Description: Adverse events during treatment

    Measure: Adverse events

    Time: 2 weeks
    140 A Phase I/II Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) for the Treatment of Adults With COVID-19

    This study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in patients with moderate COVID-19 disease.

    NCT04365101
    Conditions
    1. Coronavirus
    2. Coronavirus Infection
    3. Severe Acute Respiratory Syndrome Coronavirus 2
    4. Pneumonia
    5. Pneumonia, Viral
    6. Lung Diseases
    7. Respiratory Tract Disease
    8. Respiratory Tract Infections
    9. Coronaviridae Infections
    10. Nidovirales Infections
    11. RNA Virus Infections
    12. Virus Disease
    13. Immunologic Disease
    14. ARDS
    15. Immunologic Factors
    16. Physiological Effects of Drugs
    17. Antiviral Agents
    18. Anti-infective Agents
    19. Analgesic
    20. Analgesics
    21. Antimetabolites, Antineoplastic
    Interventions
    1. Biological: CYNK-001
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Virus Diseases Coronavirus Infections Severe Acute Respiratory Syndrome RNA Virus Infections Pneumonia, Viral Coronaviridae Infections Nidovirales Infections Pneumonia Lung Diseases Respiratory Tract Diseases Immune System Diseases
    HPO:Abnormal lung morphology Pneumonia Respiratory tract infection

    Primary Outcomes

    Description: Number and severity of adverse events

    Measure: Phase 1: Frequency and Severity of Adverse Events (AE)

    Time: Up to 6 months

    Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

    Measure: Phase 1: Rate of clearance of SARS-CoV-2

    Time: Up to 6 months

    Description: Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score.

    Measure: Phase 1: Rate of clinical improvement

    Time: Up to 6 months

    Description: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.

    Measure: Phase 2: Time to Clearance of SARS-CoV-2

    Time: Up to 28 days

    Description: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.

    Measure: Phase 2: Time to Clinical Improvement by NEWS2 Score

    Time: Up to 28 days

    Secondary Outcomes

    Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

    Measure: Rate of Clearance of SARS-CoV-2

    Time: Up to 6 months

    Description: Number and severity of adverse events

    Measure: Phase 2: Frequency and Severity of Adverse Events (AE)

    Time: up to 6 months

    Description: Time to medical discharge as an assessment of overall clinical benefit

    Measure: Overall Clinical Benefit by time to medical discharge

    Time: up to 6 months

    Description: Hospital utilization will be measured as an assessment of overall clinical benefit

    Measure: Overall Clinical Benefit by hospital utilization

    Time: up to 6 months

    Description: Mortality rate will be measured as an assessment of overall clinical benefit

    Measure: Overall Clinical Benefit by measuring mortality rate

    Time: up to 6 months

    Description: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.

    Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score

    Time: Up to 28 days

    Description: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).

    Measure: Time to Pulmonary Clearance

    Time: Up to 28 days

    Description: For ventilatory support subjects, the days with supplemental oxygen-free.

    Measure: Supplemental oxygen-free days

    Time: Up to 28 days

    Description: Proportion of subjects who need invasive or non-invasive ventilation

    Measure: Proportion of subjects requiring ventilation

    Time: Up to 28 days
    141 Protective Effect of Aspirin on COVID-19 Patients

    COVID-19 has a high infection rate and mortality, and serious complications such as heart injury cannot be ignored. Cardiac dysfunction occurred in COVID-19 patients, but the law and mechanism of cardiac dysfunction remains unclear. The occurrence of progressive inflammatory factor storm and coagulation dysfunction in severe and fatal cases of NCP points out a new direction for reducing the incidence of severe and critically ill patients, shortening the length of duration in severe and critically ill patients and reducing the incidence of complications of cardiovascular diseases. Aspirin has the triple effects of inhibiting virus replication, anticoagulant and anti-inflammatory, but it has not received attention in the treatment and prevention of NCP. Although Aspirin is not commonly used in the guidelines for the treatment of NCP, it was widely used in the treatment and prevention of a variety of human diseases after its first synthesis in 1898. Subsequently, aspirin has been confirmed to have antiviral effect on multiple levels. Moreover, one study has confirmed that aspirin can inhibit virus replication by inhibiting prostaglandin E2 (PGE2) in macrophages and upregulation of type I interferon production. Subsequently, pharmacological studies have found that aspirin as an anti-inflammatory and analgesic drug by inhibiting cox-oxidase (COX). Under certain conditions, the platelet is the main contributor of innate immune response, studies have found that in the lung injury model in dynamic neutrophil and platelet aggregation. In summary, the early use of aspirin in covid-19 patients, which has the effects of inhibiting virus replication, anti-platelet aggregation, anti-inflammatory and anti-lung injury, is expected to reduce the incidence of severe and critical patients, shorten the length of hospital duration and reduce the incidence of cardiovascular complications.

    NCT04365309
    Conditions
    1. Novel Coronavirus Pneumonia
    2. Aspirin
    3. Treatment
    Interventions
    1. Drug: Aspirin 100mg
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: TTCR is defined as the study treatment (oral aspirin enteric-coated tablet) began to fever, breathing rate, blood oxygen saturation recovery, and cough relieving for at least 72 hours.

    Measure: clinical recovery time (TTCR)

    Time: not more than 14 days

    Description: Time of SARS-CoV2 in upper respiratory tract specimens overcasting detected by RT-PCR.

    Measure: the time of SARS-CoV2 overcasting

    Time: not more than 37 days
    142 Effect of Treatments in Patients Hospitalized for Severe COVID-19 Pneumonia: a Multicenter Cohort Study

    Several treatments have been used in during the Covid-19 pandemic of 2020. Using patients' registries from several hospitals in Paris, the investigators retrospectively analyzed associations between specific treatments, including but not limited to hydroxychloroquine, azithromycin, remdesivir, baricitinib, tocilizumab, sarilumab, lopinavir/ritonavir and oseltamivir; and clinical outcomes including, death and mechanical ventilation.

    NCT04365764
    Conditions
    1. Covid-19
    2. ARDS
    3. Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite of death and mechanical ventilation (i.e. intubation)

    Measure: Composite of death and mechanical ventilation

    Time: 14-days follow-up

    Secondary Outcomes

    Description: Death

    Measure: Death

    Time: 14-days follow-up

    Description: Enabled by intubation

    Measure: Mechanical ventilation

    Time: 14-days follow-up

    Description: Composite of death and mechanical ventilation

    Measure: Composite of death and mechanical ventilation

    Time: 28-days follow-up

    Description: World Health Organization score

    Measure: World Health Organization score

    Time: 14-days follow-up

    Description: World Health Organization score

    Measure: World Health Organization score

    Time: 28-days follow-up
    143 Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated With Modulation of the Gut Microbial Flora

    Italy was the first European country affected by a severe outbreak of the Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic emerged from Wuhan region (China), with a high morbidity and mortality associated with the disease. In light of its pandemic spread and the very limited therapeutic options, COronaVIrus Disease 19 (COVID-19) is considered an unprecedented global health challenge. Therefore, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19. Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.

    NCT04366089
    Conditions
    1. COVID
    2. SARS-CoV 2
    3. Pneumonia, Viral
    4. Coronavirus Infection
    Interventions
    1. Other: Oxygen-ozone therapy, probiotic supplementation and Standard of care
    2. Dietary Supplement: SivoMixx (200 billion)
    3. Drug: Azithromycin
    4. Drug: hydroxychloroquine
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Comparison between the two groups

    Measure: Delta in the number of patients requiring orotracheal intubation despite treatment

    Time: 21 days

    Secondary Outcomes

    Description: Comparison between the two groups

    Measure: Delta of crude mortality

    Time: 21 days

    Description: Comparison between the two groups

    Measure: Delta of length of stay for patients in hospital

    Time: 90 days

    Description: Comparison between the two groups

    Measure: delta in the value of interleukin (IL)-1

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of IL-6

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of IL-10

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of Tumor Necrosis Factor (TNF)-alpha

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of CD8+ CD38/ HLA-DR

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of fecal calprotectin

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of lipopolysaccharide (LPS)

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of zonulin

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of alpha1-antitrypsin

    Time: 21 days
    144 Phase I / II Clinical Trial, Multicenter, Randomized and Controlled, to Assess the Safety and Efficacy of Intravenous Administration of Allogeneic Adult Mesenchymal Stem Cells of Expanded Adipose Tissue in Patients With Severe Pneumonia Due to COVID-19

    Phase I/II clinical trial to evaluate the safety and efficacy of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cells Expanded in patients with severe COVID-19 pneumonia

    NCT04366323
    Conditions
    1. Sars-CoV2
    Interventions
    1. Drug: ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

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

    Time: 12 months

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

    Time: 28 days
    145 Thrombo Embolic Events in Critical Care Patients With Covid-19 Serious Acute Pneumopathy

    The understanding of haemostasis and inflammation cross-talk has gained considerable knowledge during the past decade in the field of arterial and venous thrombosis. Complex and delicately balanced interaction between coagulation and inflammation involve all cellular and humoral components. Elements of the coagulation system such as activated thrombin, fibrinogen or factor Xa may increase inflammation by promoting the production of pro-inflammatory cytokines, chemokines, growth factors and adhesion molecules that lead to a procoagulant state amplifying the pathological process. Recent evidence supports inflammation as a common pathogenic contributor to both arterial and venous thrombosis, giving rise to the concept of inflammation-induced thrombosis. Patients with infection of COVID-19 and severe pneumoniae seem to have higher risk of thromboembolism. Very few data are available regarding the biological disorders of coagulation in these patients. Th purpose of this project is to analyze hemostasis and coagulation of patients with infection of COVID-19 and severe pneumonia.

    NCT04366752
    Conditions
    1. COVID-19
    2. Pneumonia
    3. ARDS
    4. Hemostasis
    5. Coagulation
    Interventions
    1. Other: venous ultrasound
    2. Other: blood sample
    MeSH:Pneumonia Thromboembolism
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: The reference range for the thrombin time is usually less than 20 seconds (ie, 15-19 seconds)

    Measure: Variation of thrombin time (in secondes) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks

    Description: Variation of factor V concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Measure: Variation of factor V concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks

    Description: Variation of factor II concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Measure: Variation of factor II concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks

    Description: Variation of concentration of fibrin and fibrinogen degradation products (≥ 10 µgm/mL) in Covid-19 patients with pneumonia admitted in ICU.

    Measure: Variation of concentration of fibrin and fibrinogen degradation products (≥ 10 µgm/mL) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks
    146 The RESCUE 1-19 Trial: Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19

    This phase I/II trial studies low-dose radiation therapy as a focal anti-inflammatory treatment for patients with pneumonia or SARS associated with COVID-19 infection.

    NCT04366791
    Conditions
    1. Pneumonia
    2. Coronavirus Infection in 2019 (COVID-19)
    3. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    Interventions
    1. Radiation: Low Dose Radiation Therapy
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The rate will be reported, along with a two-sided 95% exact binomial confidence interval, using the Clopper-Pearson method. The observed extubation rate will be compared to the null rate of 20% using a two-sided binomial test. Statistical significance is assessed at the 0.05 level.

    Measure: Rate of extubation (for intubated patients)

    Time: Screening up to 28 days after radiation therapy

    Secondary Outcomes

    Description: Temperature in degrees (F)

    Measure: Clinical outcome - Temperature

    Time: Screening up to 28 days after radiation therapy

    Description: Heart rate in beats per minutes

    Measure: Clinical outcome - Heart Rate

    Time: Screening up to 28 days after radiation therapy

    Description: Systolic blood pressure in mm Hg

    Measure: Clinical outcome - Systolic blood pressure

    Time: Screening up to 28 days after radiation therapy

    Description: Oxygen saturation in percentage

    Measure: Clinical outcome - Oxygenation

    Time: Screening up to 28 days after radiation therapy

    Description: Respiratory rate in breaths per minute

    Measure: Clinical outcome - Respirations

    Time: Screening up to 28 days after radiation therapy

    Description: FI02 in percentage

    Measure: Clinical outcome - FiO2

    Time: Screening up to 28 days after radiation therapy

    Description: Positive end expiratory pressure (PEEP) in cm H20

    Measure: Clinical outcome - PEEP

    Time: Screening up to 28 days after radiation therapy

    Description: Tidal volume in mL

    Measure: Clinical outcome - Tidal volume

    Time: Screening up to 28 days after radiation therapy

    Description: Extubation/intubation events in percentage

    Measure: Clinical outcome - Intubation/Extubation events

    Time: Screening up to 28 days after radiation therapy

    Description: Survival in percentage

    Measure: Clinical outcome - Overall survival

    Time: Screening up to 28 days after radiation therapy

    Description: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.

    Measure: Radiographic outcome - Chest xray

    Time: Screening up to 28 days after radiation therapy

    Description: CT scans with volume of consolidation measured in cubic centimeters.

    Measure: Radiographic outcome - CT can

    Time: Screening up to 28 days after radiation therapy

    Description: White blood cell count in cell count x 10^3/mcL

    Measure: Serologic outcome - WBC

    Time: Screening up to 28 days after radiation therapy

    Description: Hemoglobin in gm/dL

    Measure: Serologic outcome - Hgb

    Time: Screening up to 28 days after radiation therapy

    Description: Procalcitonin in ng/mL

    Measure: Serologic outcome - Procalcitonin

    Time: Screening up to 28 days after radiation therapy

    Description: Absolute neutrophil count in cell count x 10^3/mcL

    Measure: Serologic outcome - ANC

    Time: Screening up to 28 days after radiation therapy

    Description: Creatine kinase in units/L

    Measure: Serologic outcome - Creatine kinase

    Time: Screening up to 28 days after radiation therapy

    Description: Myoglobin in ng/mL

    Measure: Serologic outcome - Myoglobin

    Time: Screening up to 28 days after radiation therapy

    Description: Albumin in gm/dL

    Measure: Serologic outcome - Albumin

    Time: Screening up to 28 days after radiation therapy

    Description: Coagulation pathway time in seconds

    Measure: Serologic outcome - PT/PTT

    Time: Screening up to 28 days after radiation therapy

    Description: D-Dimer in ng/mL

    Measure: Serologic outcome - D-Dimer

    Time: Screening up to 28 days after radiation therapy

    Description: Gamma-glutamyl transferase in units/L

    Measure: Serologic outcome - GGT

    Time: Screening up to 28 days after radiation therapy

    Description: Trygliciericdes in mg/dL

    Measure: Serologic outcome -Triglycerides

    Time: Screening up to 28 days after radiation therapy

    Description: Ferritin in ng/mL

    Measure: Serologic outcome -Ferritin

    Time: Screening up to 28 days after radiation therapy

    Description: Fibrinogen in mg/dL

    Measure: Serologic outcome -Fibrinogen

    Time: Screening up to 28 days after radiation therapy

    Description: Immune marker flow cytometry (refractive index)

    Measure: Serologic Immune markers flow cytometry

    Time: Screening up to 28 days after radiation therapy

    Description: Bilirubin in mg/dL

    Measure: Serologic outcome -Bilirubin

    Time: Screening up to 28 days after radiation therapy

    Description: Lactate Dehydrogenase in units/L

    Measure: Serologic outcome - LDH

    Time: Screening up to 28 days after radiation therapy

    Description: Creatinine in mg/dL

    Measure: Serologic outcome - Creatinine

    Time: Screening up to 28 days after radiation therapy

    Description: Estimated Glomerular Filtration Rate in mL/min/m2

    Measure: Serologic outcome - EGFR

    Time: Screening up to 28 days after radiation therapy

    Description: C-Reactive Protein in mg/L

    Measure: Serologic outcome - CRP

    Time: Screening up to 28 days after radiation therapy

    Description: Alanine Aminotransferase in units/L

    Measure: Serologic outcome - ALT

    Time: Screening up to 28 days after radiation therapy

    Description: Asparatate Aminotransferase in units/L

    Measure: Serologic outcome - AST

    Time: Screening up to 28 days after radiation therapy

    Description: Troponin-I in ng/mL

    Measure: Serologic outcome - Troponin-I

    Time: Screening up to 28 days after radiation therapy

    Description: B-Natriuretic Peptid in pg/mL

    Measure: Serologic outcome - BNP

    Time: Screening up to 28 days after radiation therapy

    Description: pH (no unit)

    Measure: Serologic outcome - Blood Gases pH

    Time: Screening up to 28 days after radiation therapy

    Description: pressure of O2 in mm Hg

    Measure: Serologic outcome - Blood Gases pO2

    Time: Screening up to 28 days after radiation therapy

    Description: pressure of CO2 in mm Hg

    Measure: Serologic outcome - Blood Gases pCO2

    Time: Screening up to 28 days after radiation therapy

    Description: Lactic Acid in mmol/L

    Measure: Serologic outcome - Lactic Acid

    Time: Screening up to 28 days after radiation therapy

    Description: Interleukin-6 in pg/mL

    Measure: Serologic outcome - IL-6

    Time: Screening up to 28 days after radiation therapy

    Description: Potassium in mmol/L

    Measure: Serologic outcome - Potassium

    Time: Screening up to 28 days after radiation therapy
    147 Evaluation of the Impact of Bacteriotherapy in the Treatment of COVID-19

    In light of its high morbidity and mortality, COronaVIrus Disease 19 (COVID-19) pandemic spread is considered an unprecedented global health challenge. Given the very limited therapeutic options available against Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic at this time, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an observational, retrospective, non-profit study on the adjuvant use of bacteriotherapy in the early control of disease progression in patients affected by COVID-19 and treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of bacteriotherapy in reducing the clinical impact of acute diarrhea, containing the progression of COVID-19 and preventing the need for hospitalization in intensive care units.

    NCT04368351
    Conditions
    1. COVID
    2. Pneumonia
    3. Diarrhea
    Interventions
    1. Dietary Supplement: SivoMixx (200 billion)
    2. Drug: Azithromycin
    3. Drug: hydroxychloroquine
    MeSH:Pneumonia Diarrhea
    HPO:Diarrhea Pneumonia

    Primary Outcomes

    Description: Comparison between the two groups. Acute diarrhea was defined as a stool with increased water content, volume, or frequency that lasts less than 14 days.

    Measure: delta of time of disappearance of acute diarrhea

    Time: 21 days

    Secondary Outcomes

    Description: Comparison between the two groups

    Measure: Delta in the number of patients requiring orotracheal intubation despite treatment

    Time: 21 days

    Description: Comparison between the two groups

    Measure: Delta of crude mortality

    Time: 21 days

    Description: Comparison between the two groups

    Measure: Delta of length of stay for patients in hospital

    Time: 21 days
    148 Platelet Inhibition With GP IIb/IIIa Inhibitor in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). A Compassionate Use Protocol

    This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).

    NCT04368377
    Conditions
    1. Pneumonia, Viral
    2. Corona Virus Infection
    3. Respiratory Failure
    4. Embolism and Thrombosis
    Interventions
    1. Drug: Tirofiban Injection
    2. Drug: Clopidogrel
    3. Drug: Acetylsalicylic acid
    4. Drug: Fondaparinux
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency Thrombosis Embolism Embolism and Thrombosis
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment

    Measure: P/F ratio

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: PaO2 difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.

    Measure: A-a O2 difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Secondary Outcomes

    Description: Number of days on continuous positive end expiratory pressure (CPAP)

    Measure: CPAP duration

    Time: From the first day of study drugs administration (T0) until day 7 post study drugs administration

    Description: Difference in intensity of the respiratory support (non invasive mechanical ventilation, CPAP, high flow nasal cannula (HFNC), Venturi Mask, nasal cannula, from higher to lower intensity, respectively) employed at baseline and at 72 and 168 hours after study treatment initiation

    Measure: In-hospital change in intensity of the respiratory support

    Time: At baseline and 72 and 168 hours after treatment initiation

    Description: Difference in partial pressure of carbon dioxide in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: PaCO2 difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in concentration of bicarbonate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: HCO3- difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in concentration of lactate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: Lactate difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in hemoglobin concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.

    Measure: Hb difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in platelet concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.

    Measure: Plt difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Any major or minor adverse effect occuring during and after the administration of the study drug (e.g. bleeding)

    Measure: Adverse effects

    Time: From the first day of study drugs administration until day 30 post study drugs administration
    149 Intelligence-based Remote Pulmonary Rehabilitation and Efficacy Among Discharged COVID-19 Patients

    The noval coronavirus disease 2019 (COVID-19) would cause physical and psychological dysfunctions in infected patients. We expect that an intelligence-based remote pulmonary rehabilitation scheme could improve patients' health status after hospital discharge. The intelligence-based remote pulmonary rehabilitation program is designed in a real-world and prospective manner, aiming to evaluate the efficacy of rehabilitation among 200 patients in the epicenter of China (Wuhan City) according to their varied adherence. An eight-week rehabilitation scheme, including two weeks for physicians and physiotherapists remotely guided training, and six weeks for patient self-management, will be addressed. The primary outcome of current study is six-minute walking distance and lung function, and secondly respiratory muscle strength, physical fitness assessment, symptoms and quality of life, etc. will also be assessed. Recruited patients will be followed up at week 2, 4, 8 after enrollment and at month 1, 3, 6, 12 after the rehabilitation training completed, respectively. The study has been approved by the ethics committee of China-Japan Friendship Hospital and three participating centers in Wuhan City.

    NCT04368793
    Conditions
    1. COVID-2019 Pneumonia
    2. Pulmonary Rehabilitation
    Interventions
    1. Behavioral: Remote pulmonary rehabilitation
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Walking distance within six minutes

    Measure: Six-minute walking distance (6MWD)

    Time: One year

    Description: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), etc.

    Measure: Pulmonary function

    Time: One year

    Secondary Outcomes

    Description: Maximal inspiratory pressure, maximal expiratory pressure, etc.

    Measure: Respiratory muscle strength

    Time: One year

    Description: Two-minute walking test, short physical performance battery, grip strength of both upper limbs, knee extension strength of both lower limbs, etc.

    Measure: Physical fitness assessment

    Time: One year

    Description: Modified British Medical Research Council (mMRC) dyspnea scale, etc.

    Measure: Symptom

    Time: One year

    Description: Self-training depression scale (SDS) and self-rating anxiety scale (SAS)

    Measure: Psychological evaluation

    Time: One year

    Description: 36-item short-form health survey (SF-36), etc.

    Measure: Quality of life

    Time: One year

    Description: International physical activity questionnaire (IPAQ)

    Measure: Physical activity

    Time: One year

    Description: Proportions of returning to routine work and normal life

    Measure: Proportion of returning to society

    Time: One year
    150 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
    151 A Trial of Ozone Auto-hemotherapy in Adults Hospitalized With Covid-19 Pneumonia

    This is a multicenter, randomized, controlled, open-label clinical trial testing the use of ozone auto-hemotherapy in hospitalized patients with Covid-19 pneumonia. Eligible patients will be randomly assigned to receive either ozone auto-hemotherapy plus standard treatment, or standard treatment alone. Patients in the ozone auto-hemotherapy group will receive treatment mixing 100-200ml of blood with ozone at a concentration of 40 μg / mL with a gas volume of 200 ml. Treatment will occur every 12h during 5 days. Standard treatment will be the one used in each hospital participating in the trial. All analyses will be done according to the intention-to-treat principle

    NCT04370223
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: Ozone auto-hemotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Rate of patients achieving improvement in clinical condition at day 14 after recruitment

    Time: 14 days

    Secondary Outcomes

    Description: mortality

    Measure: Mortality at day 28

    Time: 28 days

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Rate of patients achieving improvement in clinical condition at day 28 after recruitment

    Time: 28 days

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Rate of patients achieving improvement in clinical condition at day 7 after recruitment

    Time: 7 days

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Time to clinical improvement or hospital discharge

    Time: 28 days

    Description: Ventilator-free days from last extubation day until day 28 after recruitment

    Measure: Number of ventilator-free days at 28 days

    Time: 28 days

    Description: Days hospitalized

    Measure: Hospital length of stay

    Time: 28 days

    Description: Number of days until a 2-fold decrease in ferritin (ng/mL)

    Measure: Time to a 2-fold decrease in ferritin

    Time: 14 days

    Description: Number of days until a 2-fold decrease in C-Protein Reactive (mg/L)

    Measure: Time to a 2-fold decrease in C-protein reactive

    Time: 14 days

    Description: Number of days until a 2-fold decrease in Dimer-D (ng/mL)

    Measure: Time to a 2-fold decrease in Dimer-D

    Time: 14 days

    Description: Number of days until a 2-fold decrease in Lactate Dehydrogenase (U/L)

    Measure: Time to a 2-fold decrease in Lactate Dehydrogenase

    Time: 14 days

    Description: Number of days until a 2-fold decrease in Neutrophils to Lymphocytes ratio

    Measure: Time to a 2-fold decrease in Neutrophils to Lymphocytes ratio

    Time: 14 days
    152 Accuracy of Lung Ultrasound in the Diagnosis of covid19 Pneumonia: a Multicenter Study in the Italian Outbreak

    Is Lung Ultrasound really useful in diagnosing COVID19? What can be the usefulness of the Lung Ultrasound in the COVID19 epidemic? In the current state of the art, Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Lung Ultrasound in the diagnosis of COVID-19 are not yet known. Alveolar-interstitial lung diseases such as viral pneumonia and ARDS seems to have a specific ultrasound pattern that distinguishes them from bacterial pneumonia, preferentially represented by B lines, morphological irregularity of the pleural line, and small subpleural consolidations, but they could share these patterns with other pathologies, reducing specificity. In Italy, the Lung Ultrasound represents a consolidated method for the evaluation and management of all patients who come to the ER, and what we are sure of is its high sensitivity in identifying pathological patterns. Our preliminary data suggest that Lung Ultrasound is highly reliable not to include but to exclude the diagnosis of COVID-19 in patients with respiratory symptoms.

    NCT04370275
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Lung Ultrasound accuracy in rule-out of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards

    Measure: Negative Predictive Value of Lung Ultrasound in the diagnosis of COVID-19

    Time: 30 days

    Secondary Outcomes

    Description: Lung Ultrasound accuracy in rule-in of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards

    Measure: Positive Predictive Value of Lung Ultrasound in the diagnosis of COVID-19

    Time: 30 days

    Measure: Sensitivity and Specificity of Lung Ultrasound in the diagnosis of COVID-19

    Time: 30 days
    153 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
    154 A Double-blind, Randomized Study Versus Placebo of Avdoralimab (IPH5401), an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia

    The primary objective of this trial is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).

    NCT04371367
    Conditions
    1. COVID
    Interventions
    1. Biological: avdoralimab
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: number of patients alive and discharged from the hospital at Day 14 for COVID-19 severe pneumonia patients who don't require hospitalization in ICU

    Measure: Number of patients alive and no longer hospitalized at D14

    Time: day 14

    Description: Number of days without mechanical ventilation at Day 28 for COVID-19 related Acute Respiratory Distress Syndrome (ARDS) Patients hospitalized in ICU

    Measure: Number of ventilator-free days at Day 28 (VFD28)

    Time: day 28

    Secondary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: day 28
    155 Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019

    The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 has seen numerous patients experiencing severe acute lung injury (ALI), which developed into severe respiratory distress syndrome (ARDS). The mortality was as high as 20% -40%. Due to the lack of effective antiviral treatments, supporting treatment is the predominant therapy for COVID-19 pneumonia. Its cure is essentially dependent on the patient's immunity. While the immune system eliminates the virus, numerous inflammatory cytokines are produced and a cytokine storm occurs in severe cases. Mesenchymal stem cells (MSCs) play an important role in injury repair and immune regulation, showing advantageous prospects in the treatment of COVID-19 pneumonia. MSCs prevent cytokine storms by retarding the TNF-α pathway, alleviate sepsis by modulating macrophages, neutrophils, NK cells, DC cells, T lymphocytes and B lymphocytes. After infused, MSCs aggregate in the lungs, improve the lung microenvironment, protect alveolar epithelia, and improve pulmonary fibrosis and pulmonary function.

    NCT04371601
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Oseltamivir
    2. Drug: hormones
    3. Device: oxygen therapy
    4. Procedure: mesenchymal stem cells
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement of pulmonary function

    Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test

    Time: 12 months

    Secondary Outcomes

    Description: Cytokines level

    Measure: Detection of TNF-α levels, IL-10 levels

    Time: 1,3,6,12months

    Description: Immunological status

    Measure: Detection of immune cells that secret cytokines, including CXCR3+, CD4+, CD8+, NK+ cells, and regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells).

    Time: 1,3,6,12months

    Description: Improvement of pulmonary function

    Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test

    Time: 1,3,6months

    Description: Infection biomarkers

    Measure: Changes of c-reactive protein and calcitonin

    Time: 1,3,6,12months
    156 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia

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

    NCT04372186
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Placebo
    2. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28

    Time: Up to Day 28

    Secondary Outcomes

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

    Time: Up to Day 28

    Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

    Time: Up to Day 28

    Measure: Mortality Rate by Day 28

    Time: Up to Day 28

    Measure: Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen)

    Time: Up to Day 28

    Measure: Percentage of Participants with Adverse Events

    Time: Up to Day 60

    Measure: Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection

    Time: Up to Day 60

    Measure: Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline)

    Time: Up to Day 60
    157 VALIDATION OF A SEVERITY SCORE TO IDENTIFY PATIENTS ADMITTED FOR COVID-19 PNEUMONIA AT HIGH RISK FOR AN INTENSIVE APPROACH

    The outbreak of the coronavirus disease 2019 (COVID-19), first merged in China in December 2019, is now becoming a Public Health Emergency, recently confirmed as a pandemic disease by the World Health Organization. In particular, since February 2020, a rapidly growing number of cases has been identified in Italy. The clinical picture of ranges from asymptomatic cases, mild upper respiratory tract infections to severe pneumonia with respiratory failure and death. In most severe cases, COVID-19 disease may be complicated by acute respiratory distress syndrome (ARDS), septic shock and multiorgan failure. It results fundamental to early identify those subjects who rapidly may worsen their clinical status, often requiring an intensive care unit (ICU) admission. It has been showed that, mainly in more severe forms of SARS-Cov-2 disease, there is the development of an hyperinflammatory status resembling a cytokine storm syndrome, as already reported in SARS patients. A recent study by Haung et al. reported that patients with COVID-19 infection showed high amounts of IL1B, IFN-gamma, IP10 and MCP1, probably linked to activated T-helper1 (Th1) cell responses. Those requiring ICU admission had higher levels of cytokines than those subjects not requiring ICU admission, thus suggesting that cytokine storm was associated with disease severity. A similarity between cytokine profile of COVID-19 disease and secondary haemophagocytic syndrome (sHLH) has been reported. Therefore, it was suggested to screen all patients with severe COVID-19 infection both for hyperinflammatory markers (like ferritin), and the HScore commonly used to generate a probability for diagnosis of sHLH (8), which includes some laboratory parameters like triglycerides, fibrinogen, ferritin, serum aspartate aminostransferase. Based on our experience on patients affected by pneumonia from Covid19, we have observed that those subjects with a more severe prognosis might have some predictive markers. We intend to verify if these markers can identify those subjects with Covid19 infection who need a more intensive therapy and to find a prognosis score.

    NCT04372199
    Conditions
    1. COVID
    2. Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: To identify the best predictors of critical coronavirus pneumonia and to realize a simple severity score able to early classify high-risk individuals admitted to Internal Medicine Department for COVID-19 disease, needing an intensive approach

    Time: 1 month
    158 Epidemiology and Outcome of Ventilator-associated Pneumonia Among Critically Ill COVID-19 Patients

    The aim of this study is to determine the risk factors for development of ventilator-associated pneumonia (VAP) and to identify the prognostic factors of VAP among Coronavirus Disease 2019 (CoViD-19) patients. We hypothesized that CoViD-19 serves as a high risk factor for the development of VAP and it affects clinical outcome measures negatively.

    NCT04372576
    Conditions
    1. Ventilator Associated Pneumonia
    2. Corona Virus Infection
    Interventions
    1. Diagnostic Test: Assessment of ventilator-associated pneumonia criteria
    MeSH:Pneumonia, Ventilator-Associated Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: 28-day all-cause mortality

    Time: at study completion, anticipated 5 months

    Secondary Outcomes

    Measure: Days of mechanical ventilation

    Time: average time frame expected 2-3 weeks

    Measure: ICU length-of-stay

    Time: average time frame expected 3-4 weeks

    Measure: Antibiotic utilization

    Time: average time frame expected 3-4 weeks (at discharge from ICU)

    Measure: Ventilator-associated pneumonia rate

    Time: at study completion, anticipated 5 months
    159 Antithrombotic Therapy to Ameliorate Complications of COVID-19

    Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host inflammatory response and activation of coagulation pathways. Macro- and micro-vascular thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic, anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive randomized controlled trial will determine whether therapeutic anticoagulation with heparin (subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus usual care reduces the need for intubation or death in hospitalized patients with COVID-19 not initially requiring invasive mechanical ventilation. The trial uses an adaptive design which was chosen to overcome limitations in available data to inform a priori estimation of event rates and possible effect sizes. The adaptive design also includes response-adaptive randomization based on baseline D-dimer level, probing for differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian adaptive randomized trial will stop at a conclusion 1) when the posterior probability that the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when the posterior probability that the proportional odds ratio is greater than 1.2 is less than 10% (definition of futility) or; 3) when the posterior probability that the proportional odds ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a maximum of 3,000 patients, although in many simulations the trial may require fewer patients. The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to accelerate evidence generation.

    NCT04372589
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Drug: Heparin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation, or death.

    Measure: Intubation and mortality

    Time: 30 days

    Secondary Outcomes

    Measure: All-cause mortality

    Time: 30 days and 90 days

    Description: Invasive mechanical ventilation

    Measure: Intubation

    Time: 30 days

    Description: Days alive outside of the hospital through 30 days following randomization

    Measure: Hospital-free days

    Time: 30 days

    Description: Number of days alive outside of the ICU through 30 days following randomization

    Measure: ICU-free days

    Time: 30 days

    Description: Number of days alive without the use of a ventilator through 30 days following randomization.

    Measure: Ventilator-free days

    Time: 30 days

    Description: The use of non-invasive mechanical ventilation or high flow nasal cannula

    Measure: Non-invasive ventilation

    Time: 30 days

    Description: Number of days alive without the use of vasopressors/inotropes and ventilation (including high flow nasal cannula >30 L/min and FIO2 >40%) through 21 days following randomization, ranked with death at anytime during 21 days as -1

    Measure: Organ support-free

    Time: 21 days

    Measure: Myocardial infarction

    Time: 30 days and 90 days

    Measure: Ischaemic stroke

    Time: 30 days and 90 days

    Measure: Venous thromboembolism

    Time: 30 days and 90 days

    Description: As defined by the International Society on Thrombosis and Haemostasis (ISTH)

    Measure: Major bleeding

    Time: Intervention period (maximum 14 days)

    Description: Laboratory-confirmed

    Measure: Heparin-induced thrombocytopenia (HIT)

    Time: Intervention period (maximum 14 days)
    160 Early Short Course Corticosteroids in Hospitalized Patients With COVID-19

    The investigators intend to study the role of early use of methylprednisolone in the hospitalized patients with a diagnosis of COVID-19 pneumonia.

    NCT04374071
    Conditions
    1. COVID
    2. Pneumonia, Viral
    Interventions
    1. Drug: Methylprednisolone
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of patients transferred to ICU is each of the groups

    Measure: Transfer to Intensive care unit (ICU)

    Time: 14 days followup for every patient in each group

    Description: Number of patients that needed mechanical ventilation in each of the groups

    Measure: Need for Mechanical Ventilation

    Time: 14 days followup for every patient in each group

    Description: Number of patients who died in each of the groups

    Measure: Mortality

    Time: 14 days followup for every patient in each group

    Secondary Outcomes

    Description: Number of patients who developed ARDS of varying severity per Berlin classification in each of the groups

    Measure: Development and Severity of ARDS

    Time: 14 days followup for every patient in each group

    Description: LOS in each of the groups

    Measure: Length of hospital stay (LOS).

    Time: 14 days followup for every patient in each group
    161 Efficacy and Safety of High-Titer Anti-SARS-CoV-2 (COVID19) Convalescent Plasma for Hospitalized Patients With Infection Due to COVID-19 to Decrease Complications: A Phase II Trial

    This is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.

    NCT04374565
    Conditions
    1. Corona Virus Infection
    2. SARS-C
    3. SARS-CoV 2
    4. SARS Pneumonia
    5. Pneumonia
    Interventions
    1. Drug: High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.

    Measure: Transfer to ICU

    Time: Days 0 - 60

    Description: Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.

    Measure: 28 day mortality

    Time: Days 0 - 60

    Secondary Outcomes

    Description: Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.

    Measure: Cumulative incidence of serious adverse events

    Time: Days 0 - 60

    Description: Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.

    Measure: Rates and duration of SARS-CoV-2

    Time: Days 0, 7, 14, and 21

    Description: Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.

    Measure: Serum of plasma antibody titer to SARS-CoV-2

    Time: Days 0, 7, 14, and 28

    Description: Blood will be collected and analyzed for cellular and humoral response.

    Measure: Cellular and humoral immune response

    Time: Days 0, 7, 14, 28

    Description: All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.

    Measure: Supplemental oxygen free days

    Time: Days 0-28

    Description: All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.

    Measure: Ventilator free days

    Time: Days 0 - 28

    Description: All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.

    Measure: ICU free days

    Time: Days 0 - 28

    Description: The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.

    Measure: Sequential organ failure assessment score

    Time: days 0, 1, 4, 7, 14, 21, 28

    Description: Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.

    Measure: Need for vasopressors

    Time: Days 0 - 60

    Description: Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.

    Measure: Need for renal replacement therapy

    Time: Days 0 - 60

    Description: Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.

    Measure: Need for extracorporeal membrane oxygenation (ECMO)

    Time: Days 0 - 60

    Description: Will be calculated from the date the patient entered the hospital until they were discharged.

    Measure: Hospital length of stay (LOS)

    Time: Days 0-60

    Description: Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.

    Measure: ICU LOS

    Time: days 0 - 60

    Description: All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.

    Measure: Grade 3 or 4 Adverse Events (AEs)

    Time: days 0 - 60
    162 Sodium Bicarbonate for Treatment of COVID-19 Pneumonia:A Preliminary Prospective Controlled Crossover Study

    To report the possible role of S.B 8.4% in the treatment of COVID-19pneumonia.

    NCT04374591
    Conditions
    1. Pneumonia
    2. Covid19
    Interventions
    1. Drug: Sodium Bicarbonate
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: defined as return of body temperature and relief of cough for more than 72 hours measured in days

    Measure: Time to clinical recovery

    Time: 7 days

    Secondary Outcomes

    Description: assessed by Chest CT defined as exacerbated, unchanged, moderately improved (with less than 50% pneumonia resolved) and significantly improved (with more than 50% pneumonia resolved).

    Measure: Pulmonary recovery status

    Time: 7 days
    163 Prevalence of Long-term Respiratory Complications of Severe SARS-CoV-2 Pneumonia

    Studies performed after coronavirus epidemics (severe acute respiratory syndrome coronavirus, SARS-CoV and Middle East respiratory syndrome coronavirus, MERS-CoV) have shown a long-term impact on respiratory morbidity, musculoskeletal and psycho-social repercussions. Patients with SARS-CoV pneumonia had fibrotic pulmonary sequelae at 45 days (lower DLCO in 27.3% of cases and radiological lesions in 21.5% of cases). In the MERS-CoV pneumonia study, patients had radiological sequelae in 33% of cases and the 12-month evaluation showed persistence of radiological abnormalities in 23.7% of the cases despite an improvement in respiratory function. Clinical presentation and therapeutic management of severe SARS-CoV-2 infection are in part similar to those induced by SARS-CoV and MERS-CoV. Long-term respiratory complications are therefore expected.

    NCT04376840
    Conditions
    1. Severe SARS-CoV2 Pneumonia
    Interventions
    1. Other: Blood sample and data record
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Interstitial lung disease diagnosed with a thoracic CT-scan

    Measure: medium-term respiratory complications

    Time: 3 months

    Secondary Outcomes

    Description: Interstitial lung disease diagnosed with a thoracic CT-scan

    Measure: long-term respiratory complications

    Time: 12 months
    164 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
    165 Pilot Study on the Feasibility of Low Dose Radiotherapy for SARS-Cov-2 Pneumonitis (COVID-19 Low Dose Radiotherapy - COLOR 19)

    Low-dose radiotherapy treatment delivered to both lungs in patients with immune-related pneumonia following COVID-19 infection is backed up by biological and clinical bases that justify its use as a possible therapeutic option in these patients. This is a preliminary exploratory study (non-pharmacological interventional) to evaluate the feasibility and tolerability of low-dose radiotherapy treatment of SARS-Cov-2 immune-mediated pneumonia, for the subsequent implementation of a phase II study.This is a preliminary, monocentric, single-arm, interventional, non-pharmacological exploratory study. All enrolled patients will be treated with low-dose radiotherapy. Participants will undergo irradiation of the lungs, administered in a single fraction at the average prescription dose of 0.7 Gy (further details in the dedicated section).

    NCT04377477
    Conditions
    1. COVID-19
    Interventions
    1. Radiation: Single fraction whole lung radiotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia, for the purpose of the subsequent implementation of a phase II study; lenght of hospital stay will be recorded

    Measure: Lenght of hospital stay (days)

    Time: Six months

    Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia; the number of intensive care unit admissions will be recorded

    Measure: Number of Intensive Care Unit admissions

    Time: Six months

    Secondary Outcomes

    Description: Variation of the patient's score according to the Brescia COVID-19 Respiratory Severity Scale (minimum value 0, maximum value 8; higher scores mean a worse outcome) with baseline, assessed at 3, 6 and 10 days after treatment.

    Measure: Variation of the Brescia COVID-19 Respiratory Severity Scale after treatment

    Time: 3, 6 and 10 days

    Description: Evaluation of the safety and tolerance of the low-dose radiotherapy treatment of SARS-Cov2 ( using the CTCAE 5.0 scale)

    Measure: Occurence of CTCAE 5.0 adverse events

    Time: 10 days and 6 months

    Description: Variation of the radiological findings, assessed by chest X-ray (performed 3 and 6 days after treatment) and defined according to the Brixia scoring system (0-18 scale, with 18 meaning the worse outcome)

    Measure: Variation of the chest X-ray radiological findings according to Brixia scoring system

    Time: 3 and 6 days
    166 The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation

    Title: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation. This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death. This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.

    NCT04377750
    Conditions
    1. Covid19 Pneumonia
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: One-month mortality rate .

    Measure: Survival

    Time: One-month
    167 Evaluation of Demographic and Clinical Parameters on Admission and Medications Used for Comorbidities in Patients With Covid-19 Pneumonia: A Single Center Experience in Turkey

    Investigators will recruit patients diagnosed with COVID-19 pneumonia between March 11th, 2020 and April 15th, 2020 in emergency, internal medicine and cardiology outpatient clinics, retrospectively and analyze their clinical and demographic features on admission in regard to their medications used for chronic diseases regularly.

    NCT04379310
    Conditions
    1. Covid-19
    Interventions
    1. Drug: ACE Inhibitors and Calcium Channel Blockers
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: number of segments involved on admission

    Measure: extend of lung involvement

    Time: 1 week

    Description: hypoxia

    Measure: oxygen saturation on admission

    Time: 2 week
    168 Low-dose Computed Tomography in COVID-19 Pneumonia: a Prospective Moscow Study

    Hypothesis: low-dose chest computed tomography, has the same accuracy for the diagnosis of pneumonia compared to the routine protocol. In total, 230 patients are planned to be enrolled in the study. Each patient will have 2 studies (routine chest CT and low-dose chest CT) sequentially during one visit to the computed tomography room.

    NCT04379531
    Conditions
    1. Pneumonia
    2. Coronavirus Infection
    Interventions
    1. Diagnostic Test: Low-dose Chest CT
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A standardized scale CT1-CT4 will be used. The expected correlation percentage is 90%.

    Measure: Evaluate the correlation between standard CT and low-dose CT scans for the detection of community-acquired pneumonia.

    Time: Upon completion, up to 1 year

    Secondary Outcomes

    Description: Expected threshold - 10 mm.

    Measure: Threshold value of the infiltration zone size detected by low-dose CT scan compared to standard CT scan.

    Time: Upon completion, up to 1 year

    Description: Expected number - more than two zones.

    Measure: Number of infiltration zones of pulmonary parenchyma corresponding to viral pneumonia detected by low-dose CT scan in comparison with standard CT scan.

    Time: Upon completion, up to 1 year
    169 Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19

    This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.

    NCT04380376
    Conditions
    1. COVID-19
    2. Viral Pneumonia
    Interventions
    1. Drug: Melphalan
    2. Other: Standard of care
    MeSH:Pneumonia, Viral Pneumonia Respiratory Aspiration
    HPO:Pneumonia

    Primary Outcomes

    Description: The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) Death Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT Hospitalized with intubation and mechanical ventilation Hospitalized on non-invasive ventilation or high flow oxygen. Hospitalized on a mask or nasal prongs. Hospitalized no oxygen therapy. Ambulatory, with limitation of activities. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.

    Measure: The changes of COVID Ordinal Outcomes Scale

    Time: baseline vs Day 14, day 28

    Description: Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.

    Measure: Percentage of the patients with Clinical Recovery

    Time: baseline vs day 7, day 14, day 28

    Description: The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.

    Measure: The changes of the Borg's scale

    Time: Baseline vs day 7, day 14, day 28

    Secondary Outcomes

    Description: Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.

    Measure: CRP level

    Time: baseline, day 7, Day 14, Day 28

    Description: Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.

    Measure: Lymphocyte count

    Time: baseline, day 7, Day 14, Day 28

    Description: Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.

    Measure: D-dimer

    Time: baseline, day 7, Day 14, Day 28

    Description: Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.

    Measure: IL-6

    Time: baseline, day 7, Day 14, Day 28

    Description: Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.

    Measure: Percentage of patients without artificial lung ventilation

    Time: baseline, day 7, Day 14, Day 28
    170 Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study

    Low radiation doses produce anti-inflammatory effects, which may be useful in the treatment of respiratory complications of COVID-19. This type of treatment is non-invasive and therefore, a priori, it can be used in all types of patients. Main objective: To evaluate the efficacy of low-dose lung irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to the pre baseline measurement. -irradiation.

    NCT04380818
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Radiation: Low-dose radiotherapy
    2. Drug: Hydroxychloroquine Sulfate
    3. Drug: Ritonavir/lopinavir
    4. Drug: Tocilizumab Injection [Actemra]
    5. Drug: Azithromycin
    6. Drug: Corticosteroid
    7. Drug: Low molecular weight heparin
    8. Device: Oxygen supply
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To evaluate the efficacy of low-dose pulmonary irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to baseline pre-irradiation measurement. . In cases of impossibility the SaFiO2 will be determined

    Measure: Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20%

    Time: Day 2 after interventional radiotherapy

    Secondary Outcomes

    Description: Lung toxicity measured according to CTCAEv5

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

    Time: Day 30 and day 90 after interventional radiotherapy

    Description: Chest CT

    Measure: Change of the radiological image

    Time: Days 7 and day 30 after interventional radiotherapy

    Description: Death of any cause

    Measure: Overall mortality

    Time: Day 15 and Day 30 after interventional radiotherapy

    Description: Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)

    Measure: Measure of pro-inflammatory interleukins

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: TGF-β (ng/ml)

    Measure: Measure of trasforming growth factor (TGF-b)

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: TNF-α (pg/ml)

    Measure: Measure of tumor necrosis factor alpha (TNF-a)

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: Overexpression of L-, E-, and P-selectin

    Measure: Determining overexpression of pro-inflammatory selectin

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: Overexpression of ICAM-1, VCAM

    Measure: Determining cell adhesion molecules (CAMs)

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: PON-1(paraoxonase and arylesterase activity) (IU/ml)

    Measure: Measure of marker of oxidative stress PON-1

    Time: Days 1, day 4 and day 7 after interventional radiotherapy
    171 Inhalation of Ciclesonide for Patients With COVID-19: A Randomised Open Treatment Study (HALT COVID-19)

    Randomized open label clinical trial carried out at study centers in Sweden, including Karolinska University Hospital, S:t Göran Hospital, Danderyd Hospital and Västmanlands Hospital. Patients with COVID-19 who are hospitalized with oxygen therapy are eligible for inclusion. Subjects are randomized to 14 days of inhalation with ciclesonide 360 µg twice daily or to standard of care. Primary outcome is duration of received supplemental oxygen therapy. Key secondary outcome is a composite outcome of death and received invasive mechanical ventilation within 30 days.

    NCT04381364
    Conditions
    1. Covid-19
    2. Pneumonia, Viral
    3. Sars-CoV2
    Interventions
    1. Drug: Ciclesonide Inhalation Aerosol
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time (in days) of received supplemental oxygen therapy (defined as being alive and discharged from hospital to home or at least 48 h of not receiving oxygen therapy during hospitalization).

    Measure: Duration of received supplemental oxygen therapy

    Time: 30 days after study inclusion

    Secondary Outcomes

    Description: Rate of and time to (in days) received invasive mechanical ventilation or all-cause death

    Measure: Invasive mechanical ventilation or all-cause death (key secondary outcome)

    Time: 30 days after study inclusion

    Description: Rate of and time to (in days) death of any cause

    Measure: All cause death

    Time: 30 days after study inclusion

    Description: Rate of and time to (in days) received invasive mechanical ventilation

    Measure: Invasive mechanical ventilation

    Time: 30 days after study inclusion

    Description: Level of remaining dyspnea symptoms according to the Modified Medical Research Council Dyspnea Scale

    Measure: Remaining dyspnea symptoms

    Time: 30-35 days and 5-7 months after inclusion
    172 Efficacy and Safety of Convalescent Plasma vs Human Immunoglobulin for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Trial

    Background: On December 2019, a new human coronavirus infection (COVID-19) was detected in China. Its infectivity and virulence characteristics caused a rapid spread, being declared pandemic on March 2020. The mortality attributed to the infection ranges between 3 and 10%. Main risk factors are age, male sex, and chronic degenerative comorbidities. Due to the absence of therapeutic options, potential alternatives such as human immunoglobulin or plasma from convalescent patients have been administered. Due to the severity of the disease and the associated mortality, it is urgent to find therapeutic alternatives. Objective: To assess the safety and efficacy of the administration of Convalescent plasma vs human immunoglobulin in critically ill patients with COVID-19 infection. Material and methods: Randomized Controlled trial of patients diagnosed with respiratory infection by COVID-19, with severe respiratory failure without indication of mechanical ventilation, or those who due to their severity are intubated upon admission. Randomization will be performed 2:1 to receive plasma from convalescent patients or human immunoglobulin. Outcomes: The primary outcome will be time to discharge from hospital for improvement. The safety outcomes will be: Kirby index (PaO2/FiO2) evolution and dead.

    NCT04381858
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Plasma from COVID-19 convalescent patient
    2. Drug: Human immunoglobulin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Mean days from admission as a suspected case of COVID with hospitalization criteria until discharge

    Measure: Mean hospitalization time

    Time: Through study completion, an average of 3 months

    Description: Mean of delta of oxigenation index (PaO2/FiO2)

    Measure: Mean Oxigenation index evolution

    Time: Through study completion, an average of 3 months

    Description: Rate of patients with evolution to severe ARDS (PaO2/FiO2 < 100)

    Measure: Rate of severe ARDS

    Time: Through study completion, an average of 3 months

    Description: Rate of Dead caused by COVID-19 related complications and time to dead caused by COVID-19 complication

    Measure: Rate and time to dead

    Time: Through study completion, an average of 3 months

    Description: Mean time with invasive mechanical ventilation

    Measure: Mean time with invasive mechanical ventilation

    Time: Through study completion, an average of 3 months

    Secondary Outcomes

    Description: Time to negativization of RT-qPCR SARS-CoV-2 test.

    Measure: Time to Viral PCR Negativization

    Time: Through study completion, an average of 3 months.
    173 High Flow Nasal Oxygen Versus Continuous Positive Airway Pressure Helmet Evaluation: A Randomized Crossover Trial in COVID-19 Pneumonia

    The purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.

    NCT04381923
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    2. Hypoxemic Respiratory Failure
    3. Pneumonia, Viral
    4. COVID
    Interventions
    1. Device: Helmet Continuous Positive Airway Pressure (CPAP)
    2. Device: High Flow Nasal Oxygen (HFNO)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insuf Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: VFD is the number of days alive and free of mechanical ventilation in the first 28 days after study enrollment. Death before 28 days will be assigned a VFD equal to 0 to penalize non-survival. In cases of repeated intubation and extubation, periods free from invasive ventilation and lasting at least 24 consecutive hours will be calculated and summed. Timing of intubation and extubation will be captured in hours, and the number of hours a patient received invasive ventilation will be used to calculate duration of ventilation.

    Measure: Ventilator-Free Days (VFD)

    Time: 28 days

    Secondary Outcomes

    Description: Days spent in the ICU and hospital after time of enrollment

    Measure: ICU and Hospital Length of Stay

    Time: 28 days

    Description: Incidence and time to intubation in days after the time of enrollment

    Measure: Intubation

    Time: 28 days

    Description: Incidence of RRT after the time of enrollment

    Measure: Renal Replacement Therapy (RRT)

    Time: 28 days

    Description: Death from any cause during after the time of enrollment

    Measure: Mortality

    Time: 28 days, 90 days
    174 Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Patients With Coronavirus Disease 2019 (COVID-19) Pneumonia and Impaired Respiratory Function

    The study will assess the efficacy and safety of DFV890 for the treatment of SARS-Cov-2 infected patients with COVID-19 pneumonia and impaired respiratory function.

    NCT04382053
    Conditions
    1. COVID 19 Pneumonia, Impaired Respiratory Function
    Interventions
    1. Drug: DFV890
    2. Drug: Standard of Care (SoC)
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.

    Measure: APACHE II severity of disease score on Day 15 or on the day of discharge (whichever is earlier)

    Time: up to Day 15

    Secondary Outcomes

    Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.

    Measure: Serum C-reactive protein (CRP) levels

    Time: up to Day 29

    Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

    Measure: Clinical status over time

    Time: up to Day 29

    Description: Proportion of participants not requiring mechanical ventilation for survival.

    Measure: Proportion of participants not requiring mechanical ventilation for survival.

    Time: Day 15, Day 29

    Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

    Measure: Proportion of participants with at least one-point improvement from baseline in clinical status

    Time: Baseline, Day 15, Day 29
    175 Treatment of Covid-19 Associated Pneumonia With Allogenic Pooled Olfactory Mucosa-derived Mesenchymal Stem Cells

    Treatment of patients with Covid-19 associated pneumonia using intravenous injection of allogenic pooled olfactory mucosa-derived mesenchymal stem cells

    NCT04382547
    Conditions
    1. COVID
    2. Covid-19
    3. Coronavirus
    4. Pneumonia
    5. Pneumonia, Viral
    6. Pneumonia, Interstitial
    7. Sars-CoV2
    Interventions
    1. Biological: Allogenic pooled olfactory mucosa-derived mesenchymal stem cells
    2. Other: Standard treatment according to the Clinical protocols
    MeSH:Pneumonia, Viral Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Number of patients cured, assessed by PCR in addition to chest CT scan

    Measure: Number of cured patients

    Time: 3 weeks

    Secondary Outcomes

    Description: MSC infusion related adverse events assessed by blood count, liver and function tests

    Measure: Number of patients with treatment-related adverse events

    Time: 3 weeks
    176 Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial

    Novel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.

    NCT04382625
    Conditions
    1. SARS-CoV-2 Pneumonia
    2. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: paO2

    Measure: Change from Baseline Oxygenation on Day 1 to Day 5

    Time: Day 1 of treatment to day 5 of treatment

    Description: FIO2

    Measure: Change from Baseline Oxygenation at Day 5

    Time: Day 1 of treatment to day 5 of treatment

    Secondary Outcomes

    Description: Length in hours

    Measure: Intensive Care length of stay

    Time: Day 0 to Day 28

    Description: Length in hours

    Measure: Required Mechanical Ventilation

    Time: Day 0 to Day 28

    Description: Length in hours

    Measure: Required Oxygen supplementation

    Time: Day 0 to Day 28

    Description: Length in hours

    Measure: Hospitalization length of Stay

    Time: Day 0 to Day 28

    Description: Date of Death

    Measure: Mortality

    Time: Day 0 to Day 28

    Description: Cardiologist Diagnostic Documentation

    Measure: Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia

    Time: Day 0 to Day 28

    Description: Cardiologist Diagnostic Documentation

    Measure: Cardiac Arrhythmia - Ventricular Tachycardia

    Time: Day 0 to Day 28

    Description: Cardiologist Diagnostic Documentation

    Measure: Cardiac Arrhythmia - Lengthening QTc

    Time: Day 0 to Day 28
    177 A Phase 2, Randomized, Placebo-controlled, Participant and Investigator Blinded, Multi-center Study to Assess Efficacy and Safety of MAS825 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function

    The study will assess the efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function

    NCT04382651
    Conditions
    1. COVID-19 Pneumonia, Impaired Respiratory Function
    Interventions
    1. Drug: MAS825
    2. Drug: Matching placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.

    Measure: APACHE II severity of disease score on Day 15 or on day of discharge (whichever is earlier)

    Time: Up to 15 days

    Secondary Outcomes

    Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.

    Measure: Serum C-reactive protein (CRP levels)

    Time: Up to 15 days

    Description: Ferritin is a blood test marker for inflammation in the body. For a standard Ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline Ferritin as a covariate.

    Measure: Ferritin levels

    Time: Up to 15 days

    Description: Proportion of participants without the need for invasive mechanical ventilation for survival.

    Measure: Proportion of participants without the need for invasive mechanical ventilation

    Time: Day 15, Day 29

    Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

    Measure: Proportion of participants with at least one level improvement in clinical status

    Time: Day 15, Day 29

    Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). -Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (noninvasive ventilation or highflow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

    Measure: Clinical status over time

    Time: Up to 15 days
    178 Effects of Neuromuscular Electrical Stimulation Therapy on Physical Function in Patients With COVID-19 Associated Pneumonia: Study Protocol of a Randomized Controlled Trial

    Neuromuscular electrical stimulation (NMES) has been considered as a promising approach for the early rehabilitation of patients in and/or after the intensive care unit (ICU). Aim of this study is to evaluate the NMES effect on physical function of COVID-19 patients.

    NCT04382729
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Other: Neuromuscular Electrical Stimulation
    2. Other: Physical Therapy Exercise
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The SPPB score is a composite measure assessing standing balance (ability to stand for up to 10 seconds with feet positioned in three ways: together side-by-side, semi-tandem and tandem), walking speed (time to complete a 4-m walk), and sit-to- stand performance (time to rise from a chair five times). Each task is scored out of 4 points, with the scores from the three tests summed up to give a total, with a maximum of 12 points and a minimum of 0.

    Measure: Short Physical Performance Battery (SPPB) Score

    Time: 1 week after the intervention

    Secondary Outcomes

    Description: The FIM is an 18-item, clinician-reported scale that assesses function in six areas including self-care, continence, mobility, transfers, communication, and cognition. Each of the 18 items is graded on a scale of 1-7 based on level of independence in that item (1 = total assistance required, 7 = complete independence)

    Measure: Functional Independence Measure (FIM) Scale Score

    Time: Before and 1 week after the intervention

    Description: The Fatigue Severity Scale is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle

    Measure: Fatigue Severity Scale Score

    Time: Before and 1 week after the intervention

    Description: Handgrip strength is assessed for both sides using a handheld device. Patients are instructed to perform a maximal voluntary isometric contraction by contracting their muscles as forcefully as possible for 4-5 s. The test is repeated three times for each side and the highest value is retained. Lower limb strength is assessed as the sum of knee extension and plantar flexion strength of both sides. Muscle strength is rated using the Medical Research Council (MRC) scale that ranges from 0 (no muscle contraction) to 5 (normal resistance), for a maximum score of 20 points.

    Measure: Muscle Strength

    Time: Before and 1 week after the intervention

    Description: Subjects are required to step out with the dominant leg maximally, then to step out with the other leg maximally, and then to draw and match the first leg to the second leg while maintaining body stability with either supporting leg. The distance between the start line and the tiptoe of the second step foot is measured as the double step length (sum of the first and second steps).

    Measure: Two Step Test Length

    Time: 1 week after the intervention

    Description: The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.

    Measure: Six Minutes Walking Test Distance

    Time: 1 week after the intervention

    Description: Ultrasound-derived muscle thickness is measured as the distance between the superficial and deep aponeuroses of the rectus femoris muscle (that is measured half-way along the line from the anterior-superior iliac spine to the superior border of the patella). Three consecutive static scans of the rectus femoris of both thighs are acquired in the transverse plane and the mean of six measurements (three measurements per side) is considered.

    Measure: Muscle Thickness

    Time: Before and 1 week after the intervention
    179 Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

    A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

    NCT04383535
    Conditions
    1. SARS Virus
    2. SARS-CoV-2
    3. COVID-19
    Interventions
    1. Other: Convalescent SARS COVID-19 plasma
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 30th day

    Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Secondary Outcomes

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 7th day

    Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 14th day

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Hospital discharge or intrahospital death

    Measure: Time until hospital discharge (days).

    Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

    Description: ICU discharge or ICU death

    Measure: Time until discharge from ICU (days)

    Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

    Description: Death and time to death

    Measure: Time to death

    Time: In a 30 days follow up period

    Description: Time until complete functional recovery (according to basal status).

    Measure: Time until complete functional recovery

    Time: Whenever the patient returns to basal functional status until 1 month from discharge

    Description: Percentage of participants with adverse events / serious adverse events

    Measure: Percentage of participants with adverse events / serious adverse events

    Time: In a 30 days follow up period

    Description: Percentage of patients with negative SARS-CoV-3 PCR

    Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: D Dimer plasma concentration

    Measure: D Dimer plasma concentration at Day 14th

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Ferritin plasma concentration

    Measure: Ferritin plasma concentration at Day 13th

    Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Plasma concentration of neutralizing antibodies

    Measure: Plasma concentration of neutralizing antibodies at Day 2nd

    Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Plasma concentration of neutralizing antibodies

    Measure: Plasma concentration of neutralizing antibodies at Day 7th

    Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Post-transfusion adverse reactions between study groups

    Measure: Post-transfusion adverse reactions

    Time: In a 30 days follow up period
    180 Predicting Outcomes for Covid-19 Using Sonography

    This study seeks to investigate the role of lung ultrasound in caring for Covid-19 positive patients and whether it can be used to predict patient deterioration. This information will be vital for healthcare workers who seek to identify Covid-19 pneumonia or patients at risk for deterioration early in the disease course.

    NCT04384055
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    Interventions
    1. Diagnostic Test: Lung Ultrasound
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite primary outcome of death, ICU admission, mechanical ventilation, or use of high-flow nasal cannula (categorical)

    Measure: Number of Patients Experiencing Death, ICU Admission, Mechanical Ventilation, or Use of High-Flow Nasal Cannula

    Time: 28 days from initial evaluation

    Secondary Outcomes

    Measure: Number of Patients Requiring Mechanical Ventilation

    Time: 28 days from initial evaluation

    Measure: Number of Patients Requiring Supplemental Oxygen Usage

    Time: 28 days from initial evaluation

    Measure: Duration of Supplemental Oxygen Usage

    Time: 28 days from initial evaluation

    Description: Duration of Hospitalization (days)

    Measure: Length of Stay

    Time: 28 days from initial evaluation

    Description: Descriptive analysis of ultrasound findings in Covid-19

    Measure: Characterization of Ultrasound Findings

    Time: 28 days from initial evaluation
    181 Cytokine Adsorption in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation - Randomized, Controlled, Open-label Intervention, Multi-center Trial (CYCOV-II-study)

    In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.

    NCT04385771
    Conditions
    1. Coronavirus Infection
    2. COVID
    3. SARS-CoV 2
    4. Respiratory Failure
    5. Cytokine Storm
    6. Extracorporeal Membrane Oxygenation
    Interventions
    1. Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)
    2. Device: vv-ECMO only (no cytokine adsorption)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

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

    Measure: IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement

    Time: 72 hours

    Description: time to successful ECMO-explantation within 30 days after randomization

    Measure: time to successful ECMO-explantation

    Time: 30 days

    Secondary Outcomes

    Description: Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization

    Measure: Ventilator free days (VFD)

    Time: 30 days

    Description: Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.

    Measure: Time to extubation from ventilation and explantation from ECMO

    Time: 30 days

    Description: Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.

    Measure: Overall survival time

    Time: 30 days

    Description: Days on intensive care unit (ICU)

    Measure: Days on intensive care unit (ICU)

    Time: 30 days

    Description: Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h

    Measure: Vasopressor dosage

    Time: 24, 48, 72 hours

    Description: Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h

    Measure: Fluid substitution and fluid balance

    Time: 24, 48, 72 hours

    Description: Serum lactate at 24, 48, 72 h

    Measure: Serum lactate

    Time: 24, 48, 72 hours

    Description: Urine output at 24, 48, 72 h

    Measure: Urine output

    Time: 24, 48, 72 hours

    Description: Willebrand factor at 24, 48, 72 h

    Measure: Willebrand factor

    Time: 24, 48, 72 hours

    Description: d-dimers at 24, 48, 72 h

    Measure: d-dimers

    Time: 24, 48, 72 hours

    Description: interleukin-6 levels at 24, 48, 72 h

    Measure: interleukin-6 levels

    Time: 24, 48, 72 hours

    Description: Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)

    Measure: SOFA-Score

    Time: 24, 48, 72 hours

    Description: serious complications or malfunctions related to the CytoSorb device

    Measure: serious adverse device effects

    Time: 30 days

    Description: unintended air in the ECMO system during operation of the device

    Measure: adverse event of special interest: air in the ECMO system

    Time: 30 days

    Description: unintended blood-clotting in the ECMO system during operation of the device

    Measure: adverse event of special interest: blood-clotting in the ECMO system

    Time: 30 days

    Description: major bleeding events

    Measure: adverse event of special interest: bleeding complications

    Time: 30 days
    182 Use of High Flow Nasal Cannula Oxygen During Acute Hypoxemic Respiratory Failure Related to Covid-19 and Interest of the Respiratory-oxygenation Index (ROX Index): an Observational Study

    Nasal High Flow oxygen therapy (NHF) is commonly used as first line ventilatory support in patients with acute hypoxemic respiratory failure (AHRF). It's use has been initially limited in Covid-19 patients presenting with AHRF. The aim of the study is to describe the use of NHF in Covid-19-related AHRF and report the changes in the respiratory-oxygenation index (termed ROX index) over time in these patients.

    NCT04385823
    Conditions
    1. Respiratory Syndrome, Acute, Severe
    2. Hypoxic Respiratory Failure
    3. Viral Pneumonia
    Interventions
    1. Device: patients receiving nasal high flow
    MeSH:Pneumonia, Viral Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: values of ROX index during ICU stay

    Measure: Changes in ROX index

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Secondary Outcomes

    Description: percentage of patients requiring intubation

    Measure: NHF failure

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: level of flow used with NHF

    Measure: NHF flow

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: level of inspired fraction in oxygen used with NHF

    Measure: NHF inspired fraction in oxygen

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: level of pulse oxymetry during NHF therapy

    Measure: oxygenation

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: respiratory rate during NHF therapy

    Measure: respiratory status

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: defining the values of ROX index associated with intubation

    Measure: prediction of intubation

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: defining the values of ROX index associated with NHF success (no intubation required)

    Measure: prediction of NHF success

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months
    183 Long Term Functional Outcomes of COVID-19 Patients Treated by Rehabilitation Services viaTelehealth

    This study seeks to assess the impact of physical and pulmonary rehabilitation on patients who have been diagnosed with COVID-19 in the short and long term in hopes of establishing a best practices protocol for treatment of future patients with this disease.

    NCT04385901
    Conditions
    1. SARS-CoV 2
    2. SARS Pneumonia
    Interventions
    1. Behavioral: Therapy Intervention
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Validated test demonstrating functional gait capacity and endurance; measuring change in capacity over time in 6 month increments.

    Measure: Change in 6 Minute Walk Test

    Time: From 6 to 24 months post diagnosis

    Description: Validated questionnaire assessing function and quality of life for patients with pulmonary function issues

    Measure: Change in Short Form 35 (SF-36) Questionnaire

    Time: From 6 to 24 months post diagnosis

    Secondary Outcomes

    Description: Use of grip dynamometer and isokinematic lower extremity testing to determine muscle capacity

    Measure: Change in Strength testing

    Time: From 6 to 24 months post diagnosis

    Description: Measures lung output capacity

    Measure: Change in Peak Flow Meter Test

    Time: From 6 to 24 months post diagnosis
    184 A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MSTT1041A or UTTR1147A in Patients With Severe COVID-19 Pneumonia

    This is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) compared with placebo and of UTTR1147A compared with placebo, in combination with standard of care (SOC), in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.

    NCT04386616
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: MSTT1041A
    2. Drug: MSTT1041A-matched Placebo
    3. Drug: UTTR1147A
    4. Drug: UTTR1147A-matched Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

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

    Time: Day 28

    Secondary Outcomes

    Measure: Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) of ≤2 Maintained for 24 hours

    Time: Up to 60 days

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

    Time: From Baseline up to 60 days

    Measure: Incidence of Mechanical Ventilation

    Time: Up to 60 days

    Measure: Incidence of Extracorporeal Membrane Oxygenation (ECMO)

    Time: Up to 60 days

    Measure: Ventilator-Free Days

    Time: Up to 28 days

    Measure: Incidence of Intensive Care Unit (ICU) Stay

    Time: Up to 60 days

    Measure: Duration of ICU Stay

    Time: Up to 60 days

    Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First)

    Time: Up to 60 days

    Measure: Mortality Rate at Days 7, 14, 21, 28, and 60

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

    Measure: Time to Hospital Discharge or "Ready for Discharge"

    Time: Up to 60 days

    Measure: Duration of Supplemental Oxygen

    Time: Up to 60 days

    Measure: Percentage of Participants Alive and Free of Respiratory Failure

    Time: Day 28

    Measure: Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

    Time: Up to 60 days

    Measure: Change from Baseline in Respiratory Rate

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Pulse Rate

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Systolic Blood Pressure

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Diastolic Blood Pressure

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Body Temperature

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Oxygen Saturation

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in RR, QRS, PR, QT, and QTcF Intervals, as Measured by Electrocardiogram (ECG)

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Heart Rate, as Measured by Electrocardiogram (ECG)

    Time: From Baseline up to 60 days

    Measure: Number of Participants with Clinical Laboratory Test Abnormalities in Hematology Parameters

    Time: From Baseline up to 60 days

    Measure: Number of Participants with Clinical Laboratory Test Abnormalities in Blood Chemistry Parameters

    Time: From Baseline up to 60 days

    Measure: Serum Concentration of UTTR1147A at Specified Timepoints

    Time: At predefined timepoints from Baseline until Study Completion (up to 60 days)

    Measure: Serum Concentration of MSTT1041A at Specified Timepoints

    Time: At predefined timepoints from Baseline until Study Completion (up to 60 days)

    Measure: Prevalence of Anti-Drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study

    Time: From Baseline up to 60 days
    185 Major Determinants of COVID-19 Associated Pneumonia

    Molecular testing (e.g PCR) of respiratory tract samples is the recommended method for the identification and laboratory confirmation of COVID-19 cases. Recent evidence reported that the diagnostic accuracy of many of the available RT-PCR tests for detecting SARS-CoV2 may be lower than optimal. Of course, the economical and clinical implications of diagnostic errors are of foremost significance and in case of infectious outbreaks, namely pandemics, the repercussions are amplified. False positives and false-negative results may jeopardize the health of a single patient and may affect the efficacy of containment of the outbreak and of public health policies. In particular, false-negative results contribute to the ongoing of the infection causing further spread of the virus within the community, masking also other potentially infected people.

    NCT04387799
    Conditions
    1. Pneumonia, Viral
    2. Pneumonia, Bacterial
    3. Coronavirus Infection
    4. Obstructive Lung Disease
    Interventions
    1. Diagnostic Test: Serology for Covid-19
    MeSH:Pneumonia, Bacterial Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Lung Diseases Lung Diseases, Obstructive
    HPO:Abnormal lung morphology Pneumonia Pulmonary obstruction

    Primary Outcomes

    Description: assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.

    Measure: Serology

    Time: 3 weeks

    Secondary Outcomes

    Description: to find if the combination of CT scan and serology could help us in the identification of those patients who were initially negative at laboratory testing alone.

    Measure: Efficacy of CT scan and Serology

    Time: 3 weeks

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

    Measure: Efficacy of different pharmaceutical treatments

    Time: 3 weeks
    186 Study of the Prevalence of Deep Vein Thrombosis in Patients Hospitalized in Intensive Care for Acute Respiratory Failure Linked to Pneumonia Documented With SARS-COV2

    Coronavirus 2 (SARS-CoV2) has been identified as the pathogen responsible for severe acute respiratory syndrome associated with severe inflammatory syndrome and pneumonia (COVID-19). Haemostasis abnormalities have been shown to be associated with a poor prognosis in these patients with this pneumonia. In a Chinese series of 183 patients, the hemostasis balance including thrombin time, fibrinogenemia, fibrin degradation products and antithrombin III were within normal limits. Only the D-Dimer assay was positive in the whole cohort with an average rate of 0.66 µg / mL (normal <50 µg / mL). These hemostasis parameters were abnormal mainly in patients who died during their management; the levels of D-dimers and fibrin degradation products were significantly higher while the antithrombin III was reduced. The findings on the particular elevation of D-dimers in deceased patients as well as the significant increase in thrombin time were also reported in another series. Higher numbers of pulmonary embolisms have been reported in patients with severe form of SARS-COV2 (data in press). This research is based on the hypothesis that the existence of deep vein thrombosis (DVT) could make it possible to screen patients at risk of pulmonary embolism and to set up a curative anticoagulation. The main objective is to describe the prevalence of deep vein thrombosis in patients hospitalized in intensive care for acute respiratory failure linked to documented SARS-COV2 pneumonia, within 24 hours of their admission.

    NCT04388657
    Conditions
    1. COVID
    2. Embolism and Thrombosis
    3. Pneumonia, Viral
    Interventions
    1. Diagnostic Test: Echo-Doppler
    MeSH:Pneumonia, Viral Pneumonia Thrombosis Embolism Embolism and Thrombosis
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: The primary outcome measure will be the percentage of patients with one or more DVTs from a lower extremity ultrasound scan.

    Measure: percentage of patients with one or more DVTs.

    Time: 28 days
    187 Aerosol Inhalation of the Exosomes Derived From Allogenic COVID-19 T Cell in the Treatment of Early Stage Novel Coronavirus Pneumonia

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused mass mortality in the last 3 months that necessitates urgent development of new therapeutical agents. So far there is no effective anti-viral drug to reduce viral load that has critical importance to prevent progress into severe viral pneumonia and systemic hyper inflammation state. This project is to offer a biologic agent based on T cell derived exosomes. This is a novel approach using our proprietary protocols for drug development. This clinical trial is to test the safety and efficacy of this new agent following targeted delivery by metered dose inhaler. The project have received proper approvals from the Turkish Ministry of Health and Erciyes University, Kayseri Turkey. Turk-Patent Application Number: PCT/TR2020/050302

    NCT04389385
    Conditions
    1. Corona Virus Infection
    2. Pneumonia
    Interventions
    1. Biological: COVID-19 Specific T Cell derived exosomes (CSTC-Exo)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety Assessment

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

    Time: 28 days

    Description: Time to Clinical Recovery (TTCR)

    Measure: Efficacy Assessment

    Time: 28 days

    Description: Efficacy Assessment

    Measure: The Rate of Recovery Without Mechanical Ventilator

    Time: 28 days
    188 TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial

    Multifocal interstitial pneumonia represents the most common cause of admission in intensive care units and death in SARS-CoV2 infections. In our Hospital, similarly to what reported in literature, up to 25% of admitted patients with pneumonitis requires mechanical ventilation or oro-tracheal intubation within 5-10 days. No established treatment is available for this condition. Preliminary evidence is accumulating about the efficacy of an aggressive treatment of the corona virus-induced inflammation and, in particular, investigators believe that blocking JAK1 is clinically rewarding in down-regulating IL-6 driven inflammation in patients with corona-virus infection. Thus, investigators designed a randomized controlled trial to test the hypothesis that adding Tofacitinib to the standard treatment in the early phase of COVID related pneumonitis could prevent the development of severe respiratory failure needing mechanical ventilation.

    NCT04390061
    Conditions
    1. Pneumonitis, Interstitial
    2. COVID-19
    Interventions
    1. Drug: Tofacitinib
    2. Drug: Hydroxychloroquine
    MeSH:Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150

    Measure: Prevention of severe Respiratory Failure requiring mechanical ventilation

    Time: 14 days

    Secondary Outcomes

    Description: Rate of patients needing admission to the intensive care unit

    Measure: Prevention of need of ICU admission

    Time: 28 days

    Description: Rate of patients who die due to COVID-19 related conditions

    Measure: Prevention of COVID-19 related Deaths

    Time: 28 days

    Description: Role of some clinical and laboratory factors in predicting outcome (Age, sex, smoking status, Body Mass Index (BMI), Comorbidities (Diabetes, number of comorbidities), Respiratory Failure at admission defined as PaO2/FiO2<300, Extension of Ct-scan involvement, basal level of serum IL-6, vW-Factor, Thrombomodulin, KL-6, sACE2 and SP-D )

    Measure: Identification of predictors of outcome

    Time: 14 days

    Description: Rate of severe drug-related adverse events

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: 28 days
    189 A Phase 2 Study to Evaluate LB1148 for the Treatment of Pulmonary Dysfunction Associated With COVID-19 Pneumonia

    This is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.

    NCT04390217
    Conditions
    1. COVID-19
    2. Coronavirus Disease 2019
    3. Covid19
    4. COVID-19 Pneumonia
    Interventions
    1. Drug: LB1148
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The proportion of subjects alive and free of respiratory failure at Day 28.

    Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure.

    Time: 28 Days

    Secondary Outcomes

    Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)

    Measure: Clinical status at fixed time points

    Time: Measured at 3, 5, 7, 8, 10, 14 and 28 Days

    Description: Length of hospital stay (live discharge)

    Measure: Duration of hospital stay

    Time: 28 Days

    Description: Number and proportion of patients requiring admission to the intensive care unit

    Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization

    Time: 28 Days

    Description: Length of ICU stay

    Measure: Duration of ICU stay

    Time: 28 Days

    Description: Number and proportion of patients requiring invasive mechanical ventilation

    Measure: Invasive mechanical ventilation requirements

    Time: 28 Days

    Description: Length of time patients require invasive mechanical ventilation

    Measure: Duration of invasive mechanical ventilation

    Time: 28 Days

    Description: The number and proportion of patients deceased at Day 28

    Measure: All-cause 28-day mortality

    Time: 28 Days

    Description: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Measure: Safety and tolerability of LB1148

    Time: 28 Days
    190 What is the Effect of Mesenchymal Stem Cell Therapy on Seriously Ill Patients With Covid 19 in Intensive Care? (Prospective Double Controlled Study)

    This study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery.

    NCT04392778
    Conditions
    1. Covid19
    2. Pneumonia
    3. Multiple Organ Failure
    4. Corona Virus Infection
    Interventions
    1. Biological: MSC Treatment
    2. Biological: Saline Control
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Multiple Organ Failure
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)

    Measure: Clinical improvement

    Time: 3 months

    Secondary Outcomes

    Description: Improvement of lungs assessed by CT Scan

    Measure: Lung damage improvement

    Time: 3 months

    Description: Negative, measured by RT-PCR laboratory tests for the virus

    Measure: Sars-Cov-2 viral infection laboratory test

    Time: 3 months

    Description: Cell types and numbers

    Measure: Blood test

    Time: 3 months
    191 BARICIVID-19 STUDY: MultiCentre, Randomised, Phase IIa Clinical Trial Evaluating Efficacy and Tolerability of Baricitinib as add-on Treatment of In-patients With COVID-19 Compared to Standard Therapy

    There is urgent need of an effective therapy for Covid-19. To date, the best treatment of SARS-CoV-2 infection is unknown. Baricitinib has been identified as potential treatment for 2019-nCoV acute respiratory disease, because of its immunomodulating and hypothesized antiviral activity. This is a multicenter randomized clinical trial that aims to evaluate the efficacy and safety of baricitinib in patients with SARS-CoV2 pneumonia. Patients will be randomized to receive or not baricitinib as adjunctive therapy. All patients will continue to receive the ongoing standard therapy: chloroquine/idrossichloroquine and low-molecular weight heparin (LMWH) eventually associated with ritonavir/lopinavir or darunavir/ritonavir will be allowed for all included patients. The primary endpoint measure is the efficacy of baricitinib in reducing the number of patients requiring invasive ventilation after 7 and 14 days of treatment. Secondary endpoints will be mortality rates and toxicity of baricitinib.

    NCT04393051
    Conditions
    1. Covid-19
    2. SARS-CoV 2
    3. SARS Pneumonia
    Interventions
    1. Drug: Baricitinib Oral Tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Reduction of the number of patients requiring invasive ventilation

    Measure: Need of invasive mechanical ventilation

    Time: after 7 and 14 days of treatment

    Secondary Outcomes

    Description: Proportion of any cause deaths

    Measure: Mortality

    Time: 14- and 28-days from randomization

    Description: Days from randomization to invasive mechanical ventilation

    Measure: Time to invasive mechanical ventilation

    Time: 30 days

    Description: Days from randomization to independence from non-invasive mechanical ventilation

    Measure: Time to independence from non-invasive mechanical ventilation

    Time: 30 days

    Description: Days from randomization to independence from oxygen therapy

    Measure: Time to independence from oxygen therapy

    Time: 30 days

    Description: Days from randomization to improvement in oxygenation for at least 48 hours

    Measure: Time to improvement in oxygenation for at least 48 hours

    Time: 30 days

    Description: Days of hospital stay

    Measure: Length of hospital stay

    Time: 30 days

    Description: Days of ICU stay

    Measure: Length of ICU stay

    Time: 30 days

    Description: Changes in pulmonary echography

    Measure: Instrumental response

    Time: 30 days

    Description: Rate of adverse events codified by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0

    Measure: Proportion of adverse events

    Time: 30 days
    192 Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia

    In this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.

    NCT04393948
    Conditions
    1. SARS-CoV 2
    Interventions
    1. Radiation: Phase 1
    2. Radiation: Phase 1
    3. Radiation: Phase 2
    4. Radiation: Phase 2
    5. Radiation: Phase 2
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Subjects will be treated with 100 cGy irradiation to a single (right-sided) lung (dose level 1) or 100 cGy irradiation to both lungs (dose level 2) following a 3 + 3 dose escalation scheme

    Measure: Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation

    Time: 4 days after randomization

    Description: The ordinal scale is an assessment of the clinical status on a given day. Each day, the worst (lowest) score from the previous day will be recorded as the score for that previous day. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring low flow supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care Not hospitalized

    Measure: Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization

    Time: 4 days after randomization

    Secondary Outcomes

    Measure: Improvement or worsening on the 7-point ordinal scale over additional intervals

    Time: Up to 30 days after randomization

    Measure: Rate and duration of use of supplemental oxygen

    Time: Up to 30 days after randomization

    Measure: Rate and duration of fever > 38ºC

    Time: Up to 30 days after randomization

    Measure: Rate and duration of invasive mechanical ventilation

    Time: Up to 30 days after randomization

    Measure: Duration of hospitalization

    Time: Up to 30 days after randomization

    Measure: Proportion of participants with overall survival up to 30 days after randomization

    Time: Up to 30 days after randomization

    Measure: Improvement in radiographic findings related to infection/inflammation; comparisons include on study versus baseline scans and irradiated vs. unirradiated lung in subjects randomized to receive single lung irradiation

    Time: Up to 30 days after randomization

    Measure: Treatment-emergent adverse events

    Time: Up to 30 days after randomization
    193 COVID-19 Imaging Features

    The novel coronavirus SARS-CoV2 clinically presents with pneumonia, characterised by fever, cough, dyspnea. The severity of the disease varies widely with evidence of mild disease in the majority of confirmed cases, severe pneumonia-dyspnea, hypoxia or lung involvement at imaging within 24-48 hours- and critical disease with respiratory failure, shock or multi-organ failure in particular patient cohorts. Imaging plays a key role is diagnosis and progression of this disease.

    NCT04394026
    Conditions
    1. Viral Pneumonia
    2. COVID
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluate RX imaging aspects at the time of diagnosis and until discharge.

    Measure: Describe qualitative and quantitative variables

    Time: Through study completion, an average of 5 months

    Description: Evaluate CT imaging aspects at the time of diagnosis and until discharge.

    Measure: Describe qualitative and quantitative variables

    Time: Through study completion, an average of 5 months

    Description: Correlate imaging findings to OS

    Measure: Ability of imaging to predict disease progression

    Time: Through study completion, an average of 5 months

    Description: Correlate imaging findings over time

    Measure: Ability of imaging to predict disease evolution

    Time: Through study completion, an average of 5 months

    Secondary Outcomes

    Description: Correlate imaging findings to age and sex

    Measure: Imaging findings and demographic data

    Time: Through study completion, an average of 5 months

    Description: Correlate imaging findings to laboratory values

    Measure: Imaging findings and laboratory exams

    Time: Through study completion, an average of 5 months
    194 Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers

    The host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.

    NCT04394182
    Conditions
    1. Pneumonia, Viral
    2. Cytokine Storm
    Interventions
    1. Radiation: Ultra-Low-dose radiotherapy
    2. Device: ventilatory support with oxygen therapy
    3. Drug: Lopinavir/ritonavir
    4. Drug: Hydroxychloroquine
    5. Drug: Azithromycin
    6. Drug: Piperacillin/tazobactam
    7. Drug: Low molecular weight heparin
    8. Drug: Corticosteroid injection
    9. Drug: Tocilizumab
    MeSH:Pneumonia, Viral Pne Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 2

    Time: At 2 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2

    Time: At 2 days after RT

    Secondary Outcomes

    Description: Pa02 / Fi02 > 300 mmHg

    Measure: Blood Gas Analysis at Day 2

    Time: At 2 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 2

    Time: At 2 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 5

    Time: At 5 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5

    Time: At 5 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 5

    Time: At 5 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 7

    Time: At 7 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7

    Time: At 7 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 7

    Time: At 7 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

    Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7

    Time: At 7 days after RT

    Description: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)

    Measure: Recovery time

    Time: From RT administration until hospital discharge or death

    Description: COVID-19 negativization test

    Measure: COVID-19 status

    Time: At 7 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

    Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1

    Time: At 1 month after RT

    Description: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.

    Measure: Acute Toxicity

    Time: 1-3 months after RT
    195 Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers

    The host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.

    NCT04394182
    Conditions
    1. Pneumonia, Viral
    2. Cytokine Storm
    Interventions
    1. Radiation: Ultra-Low-dose radiotherapy
    2. Device: ventilatory support with oxygen therapy
    3. Drug: Lopinavir/ritonavir
    4. Drug: Hydroxychloroquine
    5. Drug: Azithromycin
    6. Drug: Piperacillin/tazobactam
    7. Drug: Low molecular weight heparin
    8. Drug: Corticosteroid injection
    9. Drug: Tocilizumab
    MeSH:Pneumonia, Viral Pne Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 2

    Time: At 2 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2

    Time: At 2 days after RT

    Secondary Outcomes

    Description: Pa02 / Fi02 > 300 mmHg

    Measure: Blood Gas Analysis at Day 2

    Time: At 2 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 2

    Time: At 2 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 5

    Time: At 5 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5

    Time: At 5 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 5

    Time: At 5 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 7

    Time: At 7 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7

    Time: At 7 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 7

    Time: At 7 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

    Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7

    Time: At 7 days after RT

    Description: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)

    Measure: Recovery time

    Time: From RT administration until hospital discharge or death

    Description: COVID-19 negativization test

    Measure: COVID-19 status

    Time: At 7 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

    Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1

    Time: At 1 month after RT

    Description: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.

    Measure: Acute Toxicity

    Time: 1-3 months after RT
    196 Trial of Silymarin in Adults With COVID-19 Pneumonia

    A randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects

    NCT04394208
    Conditions
    1. COVID-19
    2. Viral Pneumonia Human Coronavirus
    Interventions
    1. Drug: Silymarin
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.

    Measure: Time to clinical improvement

    Time: 7-28 days

    Secondary Outcomes

    Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14

    Measure: Clinical outcome

    Time: 7-14 days

    Description: Time in days patient was intubated

    Measure: Duration of Mechanical Ventilation

    Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

    Description: Total days of hospitalization

    Measure: Hospitalization

    Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

    Description: number of days patient remained with positive RT-PCR SARS-CoV-2 swab

    Measure: Virologic Response

    Time: Randomization till discharge, up to 28 days

    Description: Any adverse events whether related to medication or not

    Measure: Adverse events

    Time: Randomization till hospital discharge, up to 28 days
    197 Low Dose Radiation Therapy for Covid-19 Pneumonia: A Pilot Study

    Radiotherapy in low doses (30 to 100 cGy) was a popular treatment of viral pneumonias until 1940s. Low dose radiation therapy (LDRT) could possibly reduce the inflammation and prevent the cytokine storm thus mitigating the severity of pneumonitis. This is a single arm study designed to assess the feasibility and clinical efficacy of low dose radiation therapy (70 cGy in single fraction) in the patients with COVID-19 pneumonia. A total of 10 eligible patients (as per inclusion criteria) will be recruited and response will be assessed based on the symptomatic improvement or deterioration by using the National Early Warning Score (NEWS). The NEWS score will be recorded on baseline and then on Day 3, Day 7 and Day 14.

    NCT04394793
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Radiation: Low dose radiation therapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: NEWS score

    Measure: Symptomatic improvement by National Early warning score (NEWS)

    Time: Day 3

    Description: NEWS score

    Measure: Symptomatic improvement by National Early warning score (NEWS)

    Time: Day 7

    Description: NEWS score

    Measure: Symptomatic improvement by National Early warning score (NEWS)

    Time: Day 14

    Description: Days

    Measure: Length of hospital stay

    Time: 30 days or date of death whichever is earlier

    Description: Number of patients

    Measure: Number of ICU admissions or deaths

    Time: 30 days
    198 Molecular Diagnosis and Prognosis of Severe Pulmonary Infection in Immunosuppressed Hosts

    Serious pneumonia is a serious inflammation of the lungs caused by various pathogens, resulting in severe bacteraemia or toxemia, which in turn causes blood pressure drop, shock, blurred consciousness, restlessness, delirium and coma, etc., and requires intensive care and treatment in intensive care unit (ICU) because of its seriousness. There is an upward trend in the number of clinically immunosuppressed host patients, including long-term use of glucocorticoids for rheumatoid immune diseases and kidney diseases, tumor chemotherapy, organ transplantation, etc. A huge risk for these patients is the diagnosis and treatment of infections, especially lung infections. We have previously observed a significant increase in mortality from severe pneumonia in immunosuppressed patients, and our recent analysis of 204 patients with novel coronavirus pneumonia found that low lymphatic counts, immunosuppression, etc. were independent risk factors for death in patients. Early diagnosis and timely treatment are the main means to reduce the mortality rate of severe pneumonia. CD55 is an important complement regulatory protein that inhibits C3 and C5 activation by blocking the formation and accelerating the decay of new C3 and C5 convertases, both of which mediate the downstream action of all three complement activation pathways, and CD55 protects host cells from complement attack. Our previous study found that CD55 was significantly elevated in patients with severe pneumonia. Therefore, this project proposes "Early diagnosis of severe pneumonia based on combination of biomarkers with new generation pathogenesis and early clinical manifestations". It is proposed to validate the predictive effects of recently discovered markers such as CD55, HBP and CD64 on severe pneumonia through prospective single-center clinical studies, explore the establishment of new predictive models for early diagnosis of severe pneumonia, and optimize the diagnosis and treatment strategy of severe pneumonia, and provide new ideas for accurate treatment of severe pneumonia.

    NCT04395066
    Conditions
    1. Severe Pneumonia
    2. Immunosuppressed Hosts
    3. Diagnosis
    Interventions
    1. Diagnostic Test: CD55
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of patient diagnosed with severe pneumonia within 28 days

    Time: 28 days
    199 A Phase I Study of ResCure™ to Treat COVID-19 Infection

    This is a Phase I open-label interventional study which will test the efficacy of ResCure™ in the treatment of patients with COVID-19 infection.

    NCT04395716
    Conditions
    1. COVID
    2. Covid-19
    3. Corona Virus Infection
    4. Sars-CoV2
    5. Coronavirus-19
    6. SARS Pneumonia
    7. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
    Interventions
    1. Biological: ResCure™
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR

    Measure: The rate of recovery of mild or moderate COVID-19 in patients using ResCure™

    Time: 12 Weeks

    Description: Reduction and/or progression of symptomatic days, reduction of symptom severity

    Measure: Reduction or progression of symptomatic days

    Time: 12 Weeks

    Description: Pulse from baseline to 12 weeks

    Measure: Assess the safety of ResCure™ via pulse

    Time: 12 Weeks

    Description: Oxygen saturation from baseline to 12 weeks

    Measure: Assess the safety of ResCure™ via oxygen saturation

    Time: 12 Weeks

    Description: EKG from baseline to 12 weeks

    Measure: Assess the safety of ResCure™ via EKG

    Time: 12 Weeks

    Description: Assess Adverse Events and Serious Adverse Events due to ResCure™

    Measure: Assess Tolerability of ResCure™

    Time: 12 Weeks
    200 A Study to Collect Bone Marrow for Process Development and Production of Bone Marrow Mesenchymal Stromal Cells to Treat Severe COVID19 Pneumonitis

    The COVID-19 pandemic, commonly referred to as "coronavirus", first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body's respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment. While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as "pneumonitis"). This inflammation is thought to be caused by their body's immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive. Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation.

    NCT04397471
    Conditions
    1. Healthy Volunteers for Bone Marrow Donation
    Interventions
    1. Procedure: Bone Marrow Harvest
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Successful identification of healthy volunteers in acceptable timeframe (i.e. within days) to donate bone marrow.

    Measure: Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe.

    Time: 3 or more participants recruited in 1 month

    Description: Successful manufacture of bone marrow-mesenchymal stromal cells suitable for clinical use

    Measure: Manufacture a cell-based product suitable for clinical use

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Secondary Outcomes

    Description: Ability to prepare a dossier acceptable to the MHRA. Success will achieved if the dossier is deemed acceptable.

    Measure: Establishment of a robust process of production

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Description: Successful manufacturing of products will be defined initially as the award of a Manufacturers Specials Licence to the CCTL to allow the manufacture of Bone Marrow-Mesenchymal Stromal Cells for compassionate use.

    Measure: Production of stability data to be used in the MHRA dossier for the COMET clinical trial.

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Description: Successful manufacturing of products will be subsequently defined by production under MA(IMP) licence, allowing for future production under CTIMP and CTA.

    Measure: Production of cell-based products to be administered to COVID-19 patients with severe pneumonitis.

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Description: Successful manufacturing of products, under MA(IMP) licence will be defined as the availability of Bone Marrow-Mesenchymal Stromal Cells to be used in the context of the COMET20 clinical trial.

    Measure: Analysis of cells for understanding production, manufacture and related research.

    Time: Successfully opening the next phase of the trial in approx. 2 months
    201 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
    202 Inhaled NO for the Treatment of COVID-19 Caused by SARS-CoV-2 (US Trial)

    The purpose of this open label, randomized, study is to obtain information on the safety and efficacy of 80 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.

    NCT04397692
    Conditions
    1. Corona Virus Infection
    2. COVID-19
    3. SARS-CoV 2
    4. Nitric Oxide
    5. Respiratory Disease
    6. Pneumonia, Viral
    7. Inhaled Nitric Oxide
    Interventions
    1. Device: Nitric Oxide delivered via LungFit™ system
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Aspiration Respiration Disorders Respiratory Tract Diseases
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to deterioration measured by need for NIV, HFNC or intubation

    Measure: Time to deterioration

    Time: 14 Days

    Secondary Outcomes

    Description: Time to non-invasive ventilation

    Measure: Time to NIV

    Time: 14 Days

    Description: Time to high flow nasal cannula

    Measure: Time to HFNC

    Time: 14 Days

    Description: Time to intubation

    Measure: Time to intubation

    Time: 14 days

    Description: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

    Measure: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

    Time: 14 days

    Other Outcomes

    Description: Need for supplemental oxygen

    Measure: Need for supplemental oxygen

    Time: 14 days

    Description: Change in viral load

    Measure: Change in viral load

    Time: 30 days

    Description: Duration of the Hospital Length of Stay (LOS)

    Measure: Duration of the Hospital Length of Stay (LOS)

    Time: 14 days

    Description: Mortality rate at Day 30

    Measure: Mortality rate at Day 30

    Time: 30 days
    203 An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants With COVID-19 Pneumonia Caused by SARS-CoV-2.

    The purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.

    NCT04397757
    Conditions
    1. COVID-19
    Interventions
    1. Biological: COVID-19 Convalescent Plasma
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Cumulative incidence of serious adverse events (SAEs) at Study Day 29.

    Measure: Participants with serious adverse events.

    Time: Up to 29 days from treatment

    Description: Severity is measured by the 8-point ordinal clinical severity scale at D29 where 1 is the best state to be in and 8 is the worst (equals death).

    Measure: Comparison of clinical severity score between patients on the experimental versus control arms;

    Time: Up to 29 days from treatment

    Secondary Outcomes

    Description: Time to recovery, defined by time to levels 1-3 on the ordinal scale

    Measure: Clinical status assessment, using 8-point ordinal scale, of convalescent plasma administration by comparing treatment vs control arms

    Time: Up to 29 days from treatment

    Description: Time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first.

    Measure: Clinical status assessment using the National Early Warning Score (NEWS) of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment, daily while hospitalized until discharge or death and on Days 15 and 29.

    Description: Oxygen-free days to Day 29.

    Measure: Oxygen-free days of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29

    Description: Incidence of new oxygenation use up to Day 29.

    Measure: Incidence of new oxygenation use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of new oxygen use up to Day 29.

    Measure: Duration of new oxygen use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of non-invasive ventilation/high flow oxygen up to Day 29

    Measure: Non-invasive ventilation/high flow oxygen days up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Incidence of non-invasive ventilation up to Day 29.

    Measure: Incidence of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of non-invasive ventilation/high flow oxygen up to Day 29

    Measure: Duration of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Ventilation/ECMO free days up to Day 29. mechanical ventilation or ECMO use during the study.

    Measure: Ventilator/ECMO free days to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Incidence of new mechanical ventilation or ECMO use up to Day 29.

    Measure: Incidence of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of new mechanical ventilation or ECMO use up to Day 29.

    Measure: Duration of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Duration of hospitalization.

    Measure: Duration of hospitalization of convalescent plasma administration by comparing treatment vs control arms

    Time: To Day 29

    Description: D14 and D28 mortality.

    Measure: Mortality of convalescent plasma administration by comparing treatment vs control arms

    Time: To Day 28

    Description: Cumulative incidence of SAEs through Day 29.

    Measure: Cumulative incidence of SAEs through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29.

    Measure: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in WBC with differential on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in WBC with differential through day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in hemoglobin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in hemoglobin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in platelets measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in platelets measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in creatinine measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in creatinine measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in glucose measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in glucose measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in bilirubin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in bilirubin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in ALT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in ALT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in AST measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in AST measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in PT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in PT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.
    204 A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia

    The primary objective of this study is determine the safety and efficacy of ACT-20-MSC (allogenic human umbilical derived mesenchymal stem cells) and ACT-20-CM (allogenic human umbilical derived mesenchymal stem cells in conditioned media) in patients with moderate to severe COVID-19 pneumonia.

    NCT04398303
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: ACT-20-MSC
    2. Biological: ACT-20-CM
    3. Biological: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Mortality at day 30

    Time: 30 days post treatment

    Secondary Outcomes

    Description: Number of ventilator-free days

    Measure: Ventilated Subjects - Ventilator Free Days

    Time: 28 days post treatment

    Description: Improvement in ventilator settings: Minute ventilation, PEEP, FiO2

    Measure: Ventilated Subjects - Improvement in Ventilator Settings

    Time: 28 days post treatment, or until off of ventilator

    Description: Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration.

    Measure: High-Flow O2 Support Subjects - Step-Down O2 Therapy

    Time: 30 days post treatment, or until off of high-flow O2 support

    Description: Respiration Rate < 30 for > 24 hours.

    Measure: High Flow O2 Support Subjects - Respiration Rate

    Time: 30 days post treatment, or until off of high-flow O2 support

    Description: Number of ICU-free days

    Measure: Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

    Description: Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation

    Measure: Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

    Description: Increased Berlin Criteria score > 24 hours

    Measure: Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
    205 The Utility of Bedside Lung Ultrasonography on Diagnosis of COVID-19 at Emergency Department

    Novel Coronavirus 2019 Disease (COVID-19) mortality is highly associated with viral pneumonia and its complications. Accurate and prompt diagnosis shown to be effective to improve outcome by providing early treatment strategies. While chest X-ray (CXR) and computerized tomography (CT) are defined as gold standard, given the advantage of being an ionized radiation free, practical technique point of care ultrasound (POCUS) is also reported as a diagnostic tool for COVID-19. There are limited studies regarding the importance of POCUS in diagnosis and review of COVID-19. Therefore the aim of this study is to evaluate the utility of bedside lung ultrasound on diagnosis of COVID-19 for patients admitted to emergency department .

    NCT04399681
    Conditions
    1. COVID
    2. Pneumonia, Viral
    Interventions
    1. Device: Bedside lung ultrasound
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Efficacy of POCUS on diagnosis of viral pneumonia caused by COVID 19

    Measure: Presence of viral pneumonia caused by COVID 19

    Time: 3 months
    206 A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia

    The objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia. This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.

    NCT04399798
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: Baricitinib
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

    Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)

    Time: 8 days

    Description: Absence of death within 8 days from enrollment

    Measure: Response to treatment: survival

    Time: 8 days

    Secondary Outcomes

    Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

    Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days

    Time: 8 days

    Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

    Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days

    Time: 15 days

    Description: To quantify mortality within 8 and 15 days

    Measure: Mortality

    Time: 8 days and 15 days

    Description: SpO2 will be assessed with the median and 25th-75th percentiles

    Measure: Peripheral capillary oxygen saturation (SpO2)

    Time: 8 days; 15 days

    Description: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles

    Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

    Time: 8 days; 15 days

    Description: Number of patients over the number of patients enrolled

    Measure: To assess the rate of patients admitted to the intensive care unit

    Time: 8 days; 15 days

    Description: Median number of days and 25th-75th percentiles

    Measure: To measure the length of hospital stay

    Time: 8 days; 15 days

    Description: To quantify 28-day mortality

    Measure: 28-day mortality

    Time: 28 days

    Description: Number of patients readmitted over the number patients enrolled

    Measure: To quantify the rate of re-admission within 28 days

    Time: 28 days

    Description: Number, type, and severity of adverse events

    Measure: To quantify the cumulative incidence and severity of adverse events

    Time: 28 days

    Description: Serial serum assessments from baseline up to 15 days

    Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;

    Time: 15 days

    Description: Serial serum assessments from baseline up to 15 days

    Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels

    Time: 15 days

    Description: Serial assessments from baseline up to 15 days for viral load persistence

    Measure: Viral load analyses

    Time: 15 days
    207 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation

    The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

    NCT04399980
    Conditions
    1. COVID 19
    2. SARS-CoV 2
    3. Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebos
    MeSH:Pneumonia Respiratory Insufficiency Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of subjects alive and off of oxygen

    Measure: Proportion of subjects alive and off of oxygen at day 14

    Time: Day 14

    Secondary Outcomes

    Description: Number of subjects that are alive

    Measure: Proportion of subjects alive at 28 days

    Time: Day 28

    Description: Number of subjects alive and without respiratory failure

    Measure: Proportion of subjects alive and without respiratory failure at 28 days

    Time: Day 28
    208 Multiparametric Evaluation of One-year Outcomes in Survivors of the Severe COVID-19 Pneumonia After Intensive Care Unit

    Pneumonia caused by infection at SARS-CoV2 may be complicated by an acute respiratory detress syndrome need to take care in intensive care unit and can lead to mechanical ventilation. COVID-19 is a pandemic disease and lot of patients will survive of severe pneumoniae at SARS-CoV2 treat in ICU. At this time, there is no data about functional prognosis at long term. This aim of this study is to evaluate the recovery of quality of life, respiratory function, neuromuscular function at long term and incidence of post-traumatic stress disorder. Patients will follow during 1year after out of ICU with 3 consultations at 3month, 6month and 12month. At each consultation patients will be evaluated about respiratory function, effort tolerance via 6minutes walking test, psychologic function with IES-R and HAD score and quality of life with SF36. The hypothesis is that patients who survived of ARDS post infection at SARS-CoV2 have persistent functional limitation and alteration of quality of life one year after being discharged from the ICU.

    NCT04401111
    Conditions
    1. COVID
    2. ARDS
    3. Quality of Life
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary outcome is the score SF36 at 3month, 6month, 12 month after discharged of ICU in study population

    Measure: Evaluation of recovery of quality of life in first year after ICU discharged in patients hospitalised for severe pneumonia at SARS-CoV2

    Time: 1 year

    Secondary Outcomes

    Description: Evaluation of functional respiratory exploratory

    Measure: Evaluation of respiratory function during first year after ICU discharged in population studied

    Time: 1 year

    Description: Mesure of the traveled distance in six-min walk test

    Measure: Evaluation at 1 year of evolution of functional exercises capacity in population studied

    Time: 1 year

    Description: Mesure of creatinine clairance and proteinuria

    Measure: Evaluation of evolution of renal function during first year after ICU discharged in population studied

    Time: 1 year

    Description: Sudy of cardiac ultrasonography parameters

    Measure: Evaluation of evolution of right and left myocardic function during first year after ICU discharged in population studied

    Time: 1 year

    Description: Occurence of post-traumatic stress disorder or anxious and depressive disorders in population studied

    Measure: Evaluation at 1 year of incidence of psychiatric pathology

    Time: 1 year

    Description: Rate of return to professional activity

    Measure: Evaluation at 1 year of consequences in professional activity in population studied

    Time: 1 year
    209 Development and Validation of Predictive Models for Intensive Care Admission and Death of COVID-19 Patients in a Secondary Care Hospital in Belgium.

    To build simple and reliable predictive scores for intensive care admissions and deaths in COVID19 patients. These scores adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guidelines. The outcomes of the study are (i) admission in the Intensive Care Unit admission and (ii) death. All patients admitted in the Emergency Department with a positive reverse transcription-polymerase chain reaction SARS-COV2 test were included in the study. Routine clinical and laboratory data were collected at their admission and during their stay. Chest X-Rays and CT-Scans were performed and analyzed by a senior radiologist. Generalized Linear Models using a binomial distribution with a logit link function (R software version X) were used to develop predictive scores for (i) admission to ICU among emergency ward patients; (ii) death among ICU patients. A first panel of Number Models with the highest AIC (BIC) was preselected. Ten-fold cross-validation was then used to estimate the out-of-sample prediction error among these preselected models. The one with the smallest prediction error was in the end singled out .

    NCT04401228
    Conditions
    1. COVID19
    2. Pneumonia, Viral
    3. Inflammatory Response
    Interventions
    1. Other: predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables?
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: admission to ICU

    Time: through study completion, an average of 1 year

    Secondary Outcomes

    Measure: death

    Time: through study completion, an average of 1 year
    210 Paediatric Post Pneumococcal Conjugate Vaccine Nasopharyngeal Carriage Study

    The investigators intend to investigate the carriage of pneumococci and other respiratory microbes since the introduction of pneumococcal conjugate vaccines (Prevenar 7 and Prevenar 13). The principal aim is to gain a collection of samples that can be used to help investigate any changes that might occur in the epidemiology of microbes that are carried in the upper respiratory tract and which may cause respiratory disease, sepsis or meningitis after the introduction of Prevenar. Nasopharyngeal and nasal swabs will be taken from up to 2,000 children aged 4 years and under in each year of the study. Swabs will be processed using traditional microbiology and molecular diagnostic techniques and isolated microbes such as S. pneumoniae further characterised using molecular methods. The investigators will also ask parents to complete a short questionnaire requesting: basic demographic data; vaccine history; recent illness; overseas travel and antibiotic usage. The study will contribute to the success of the introduction of pneumococcal conjugate vaccines and will play a central role in maintaining confidence. The study will also help provide information for future vaccine policy as further vaccines are developed against microbes which cause respiratory disease, sepsis and meningitis.

    NCT04401488
    Conditions
    1. S. Pneumoniae
    2. Pneumococcal Conjugate Vaccine
    Interventions
    1. Biological: Prevenar 7 and Prevenar 13
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To gain a collection of pneumococci and other microbes of related importance that can be used to help investigate any changes that occur in the epidemiology of pneumococcal disease since the introduction of Prevenar 13

    Measure: Collection of pneumococci

    Time: By the end of the study (31/03/2027)

    Secondary Outcomes

    Description: To use all isolated strains to help understand changes in the molecular epidemiology of pneumococci, and other relevant microbe species of the upper respiratory tract.

    Measure: Understand changes in the molecular epidemiology of pneumococci

    Time: By the end of the study (31/03/2027)
    211 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: Change from baseline in SaO2/FiO2 ratio

    Measure: Part 2: SaO2/FiO2 ratio

    Time: Baseline, Day 7

    Description: Number of days the subject was not using invasive mechanical ventilation or non-invasive positive pressure ventilation

    Measure: Part 2: Ventilator-free Days (VFDs)

    Time: Baseline through Day 28

    Secondary Outcomes

    Description: Number of days the subject was not in the ICU

    Measure: Part 2: Intensive Care Unit Free Days (ICU-free)

    Time: Baseline through Day 28

    Description: Area under the plasma concentration-time curve (AUC) in SaO2/FiO2 ratio

    Measure: Part 2: AUC in SaO2/FiO2 ratio

    Time: Baseline through Day 7

    Description: Change from baseline in SaO2/FiO2 ratio

    Measure: Part 2: SaO2/FiO2 ratio

    Time: Baseline, Day 5

    Description: Proportion of subjects with a SaO2/FiO2 ratio > 315

    Measure: Part 2: SaO2/FiO2 ratio > 315

    Time: Day 5, Day 7

    Description: Proportion of subjects discharged

    Measure: Part 2: Subjects Discharged

    Time: Day 7, 14, 21 and 28

    Description: Time to hospital discharge

    Measure: Part 2: Hospital Discharge

    Time: Baseline through up to Day 28

    Description: The subject mortality rate (all causes)

    Measure: Part 2: Mortality Rate

    Time: Day 28

    Description: Change from baseline in the modified Borg Dyspnea Score. The modified Borg Dyspnea Score is based on a 10-point scale that measures shortness of breath. Scores range from 0 (nothing at all, no shortness of breath) to 10 (maximal shortness of breath).

    Measure: Part 2: Modified Borg Dyspnea Score

    Time: Baseline through Day 7

    Description: Proportion of subjects in each category of the Clinical Status scale. The Clinical Status scale contains 6 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized'), 2 (hospitalized, not requiring supplemental oxygen), 3 (hospitalized, requiring low-flow oxygen supplementation), 4 (hospitalized, on non-invasive positive pressure ventilation or high-flow oxygen supplementation), 5 (hospitalized, on invasive mechanical ventilation, 6 (Death).

    Measure: Part 2: Clinical Status Scale

    Time: Day 7, 14, 21 and 28

    Description: Proportion of subjects in each category of Vital Status, where the categories are defined as death, discharge, or hospitalized.

    Measure: Part 2: Vital Status

    Time: Day 7, 14, 21 and 28

    Description: Proportion of subjects alive and free of ventilatory support

    Measure: Part 2: Subjects alive and free of ventilatory support

    Time: Day 28
    212 Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 and Increased Inflammatory Markers: a Phase III Randomized Clinical Trial (COVID-19 Coalition Brazil VI) (TOCIBRAS)

    The trial evaluates the efficacy and safety of Tocilizumab, which rapidly reduces the inflammation process through inhibition of IL-6 in patients with moderate to severe COVID-19 with increased inflammatory markers. There will be two arms in the trial, one receiving the best supportive care, and the other receiving it plus tocilizumab. Patients will be followed until Day 29 after randomization.

    NCT04403685
    Conditions
    1. COVID
    2. SARS Pneumonia
    3. Cytokine Release Syndrome
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of clinical status of patients on day 15 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)

    Measure: Evaluation of clinical status

    Time: Day 15 of the trial

    Secondary Outcomes

    Description: All-cause mortality from randomization to day 28

    Measure: All-cause mortality

    Time: 29 days after the randomization

    Description: Deaths that occur during hospital admission.

    Measure: Hospital Mortality

    Time: 29 days after the randomization

    Description: Improvement of SOFA scale of patients at day 8, 15 and 29 after randomization

    Measure: Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale

    Time: 29 days after the randomization (evaluations at D8 and D15)

    Description: Evaluation of clinical status of patients on the day 8, 22 and 29 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)

    Measure: Evaluation of clinical status

    Time: 29 days after the randomization (evaluations at D8 and D29)

    Description: Days alive and free from mechanical ventilation since randomization

    Measure: Ventilator free days

    Time: 29 days after the randomization

    Description: Days from randomization to independence of oxygen support

    Measure: Time until oxygen support independence

    Time: 29 days after the randomization

    Description: Number of patients that were not at mechanical ventilation at randomization and that required that support.

    Measure: Need of mechanical ventilation support

    Time: 29 days after the randomization

    Description: Number of days to mechanical ventilation for patients that were not receiving it at randomization. For patients that were not in mechanical ventilation at randomization: number of days until that support was required.

    Measure: Days to mechanical ventilation support.

    Time: 29 days after the randomization

    Description: Lenght of hospitalization stay in survivors (in days)

    Measure: Duration of hospitalization

    Time: 29 days after the randomization

    Description: Incidence of other infections (aside from SARS-CoV 2)

    Measure: Other infections

    Time: 29 days after the randomization

    Description: Incidence of thromboembolic events in patients with COVID-19

    Measure: Incidence of thromboembolic events

    Time: 29 days after the randomization

    Description: Evaluation of adverse events, as well as serious and unexpected adverse events

    Measure: Incidence of adverse events

    Time: 29 days after the randomization (specific evaluations at D8, D15 and D29)

    Other Outcomes

    Description: Correlation of inflammatory tests and cytokines with clinical outcomes: clinical status (ordinal scale), time to oxygen support independence, ventilator free days, need of mechanical ventilation and mortality

    Measure: Correlation of inflammatory tests and cytokines with clinical outcomes

    Time: 29 days after the randomization

    Description: Evaluation the kinetics of hemostasia exams, inflammatory tests, cytokines, flow cytometry of blood cells, CBC, renal and liver exams

    Measure: Exploratory evaluation of laboratory exams during hospitalization

    Time: 29 days after the randomization

    Description: Evaluation of viral clearance of SARS-CoV2 using RT-PCR analysis of nasopharyngeal swab

    Measure: Evaluation of viral clearance of SARS-CoV2

    Time: Day 8 and 15 after randomization
    213 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
    214 Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 Pneumonia: A Randomized,Open-label,Controlled Clinical Trial

    This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia

    NCT04405921
    Conditions
    1. SARS-CoV-2 Pneumonia
    2. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine 200 Mg Oral Tablet
    2. Drug: Azithromycin 250 MG
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19.

    Measure: Clinical recovery at day-14, from the start of treatment.

    Time: 14 days

    Secondary Outcomes

    Description: RT-PCR will be realized in same laboratory

    Measure: Viral Clearance via RT-PCR at day 5- 7-10 and day 14

    Time: 5- 7-10 and day 14
    215 Clinical Scores for Outcome Prediction in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation - a Retrospective Multi-center Registry Study

    The prognosis of patients with severe COVID-19 disease, whose lungs are so severely diseased that they need to be supported by veno-venous ECMO (extracorporeal membrane oxygenation), is difficult to assess so far. Previously published data from studies, case reports and case series describe a very high mortality in this patient collective. The significance of established clinical prognostic cores in this patient population has not been systematically investigated. This is aggravated by the fact that even at very specialized centers only very few patients from this collective are (can be) treated, so that valid investigations are only possible in a multicenter patient collective. In this registry study, all patients diagnosed with COVID-19 and treated with vv-ECMO in the centers participating in the study should be retrospectively examined. The primary aim of the study is to investigate 30-day survival, secondary objectives include the analysis of different clinical scores at the time of ECMO implantation.

    NCT04405973
    Conditions
    1. COVID-19
    2. SARS-CoV 2
    3. Extracorporeal Membrane Oxygenation
    4. ARDS
    Interventions
    1. Device: vv-ECMO
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: time from ECMO-implantation to death

    Measure: overall survival

    Time: 30 days

    Secondary Outcomes

    Description: time from ECMO-implantation to ECMO-explantation

    Measure: duration of ECMO treatment

    Time: 30 days

    Description: time from ECMO-implantation to extubation

    Measure: duration of ventilation treatment

    Time: 30 days

    Description: time from ECMO-implantation to ICU-discharge

    Measure: duration of initiation of ECMO treatment to ICU discharge

    Time: 30 days
    216 Awake Prone Positioning and Oxygen Therapy in Patients With COVID-19 (APRONOX)

    The prone position strategy for patients with acute respiratory distress syndrome (ARDS) is simple and cost-effective from the first description on its use in patients with acute respiratory failure to improve hypoxemia. Different studies have investigated its safety and efficacy in various clinical settings, demonstrating that its early use in combination with non-invasive mechanical ventilation (NIV) or high-flow oxygen therapy can reduce intubation rate and mortality in ARDS. In the Coronavirus disease 2019 (COVID-19) pandemic, high-value medicine and resource optimization are critical.

    NCT04407468
    Conditions
    1. COVID
    2. ARDS
    3. Pneumonia
    Interventions
    1. Procedure: Prone position
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Relationship between awake prone position and the tracheal intubation

    Measure: To analyze the relationship between the prone position and the need for orotracheal intubation.

    Time: 3 months

    Secondary Outcomes

    Description: See the relationship between the awake prone position and the SaO2/FiO2 INDEX

    Measure: The impact of the prone position on the partial oxygen saturation / inspired oxygen fraction index (SaO2 / FiO2).

    Time: 3 months

    Other Outcomes

    Description: Determine the free hours without the need for orotracheal intubation of patients in the prone position.

    Measure: Determine the free hours without the need for orotracheal intubation of patients in the prone position.

    Time: 3 months
    217 Randomised Controlled Trial Comparing High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy Not Requiring Invasive Mechanical Ventilation

    Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation. Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are: 1. More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay: 1. Death 2. Acute Myocardial Infarction [AMI] 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] 4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation 5. Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation 2. Similar in terms of major bleeding risk during hospital stay

    NCT04408235
    Conditions
    1. COVID
    2. Pneumonia, Viral
    3. Coagulation Disorder
    Interventions
    1. Drug: Enoxaparin
    MeSH:Pneumonia, Viral Pneumonia Hemostatic Disorders Blood Coagulation Disorders
    HPO:Abnormality of coagulation Abnormality of the coagulation cascade Pneumonia

    Primary Outcomes

    Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation

    Measure: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:

    Time: through study completion, up to 30 days

    Secondary Outcomes

    Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation Improvement of laboratory parameters of disease severity, including: D-dimer level Plasma fibrinogen levels Mean Platelet Volume Lymphocyte/Neutrophil ratio IL-6 plasma levels

    Measure: Any of the following events occurring within the hospital stay

    Time: through study completion, up to 30 days

    Description: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.

    Measure: Mortality at 30 days

    Time: 30 days
    218 Retrospective Change in the Ratio of Mean Platelet Volume (MPV) to Platellet(PLT) in Covid-19 Pneumonia Patients

    Morbidity, mortality and progress depends on systemic inflammation especially in ARDS patients. Previous studies claims that the proportion of mean platellet volume to platellet which can simply be determined with simple blood tests that are performed at admission, might predict the mortality in ARDS patients. Covid-19 pneumonia has a very similar clinical outlook with ARDS. Therefore we decided to research whether that proportion is legitimate for detecting the progress of Covid-19 pneumonia or not.

    NCT04408378
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Other: observation of covid 19 pneumonia
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: İt has been studied that MPV/PLT ratio can show the cl inical couses of several diseases as well as ARDS. we thought that we can identify the coronavirus pneumonia patients earlier, at admission of hospital by using the hemogrames.

    Measure: estimation of inflammatory changes in Covid 19 pneumonia by using MVP/PLT ratio

    Time: March-May 2020
    219 A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

    This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

    NCT04409262
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Remdesivir
    2. Drug: Tocilizumab
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Day 28

    Time: Day 28

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 28

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

    Time: Up to Day 28

    Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, and 21

    Time: Days 7, 14, and 21

    Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline

    Time: Up to Day 28

    Measure: Ventilator-Free Days from Randomization to Day 28

    Time: Up to Day 28

    Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline

    Time: Up to Day 28

    Measure: Duration of ICU Stay in Days

    Time: Up to Day 28

    Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.

    Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

    Time: Up to Day 28

    Measure: Mortality Rate on Days 7, 14, 21, 28, and 60

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

    Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed

    Time: Up to Day 28

    Measure: Time from Randomization to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or Time: Up to Day 28

    Measure: Duration of Supplemental Oxygen Use

    Time: Up to Day 28

    Other Outcomes

    Measure: Percentage of Participants with Adverse Events (AEs)

    Time: Up to Day 28

    Measure: Proportion of Participants with any Post-Treatment Infection

    Time: Up to Day 28

    Measure: Plasma Concentration of Remdesivir

    Time: Up to Day 28
    220 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
    221 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY

    The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.

    NCT04412252
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tofacitinib
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using ordinal scale

    Time: Day 28

    Secondary Outcomes

    Description: Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using ordinal scale

    Time: Day 14

    Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

    Time: Day 14 and Day 28

    Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Status of discharged or not requiring supplemental oxygen

    Time: Day 28

    Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

    Measure: Mortality

    Time: Day 60
    222 A Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)

    A Phase 2 study to evaluate the safety and preliminary efficacy of ATYR1923, compared to placebo, in hospitalized patients with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation

    NCT04412668
    Conditions
    1. SARS-CoV-2 (COVID-19) Severe Pneumonia
    Interventions
    1. Drug: ATYR1923 1 mg/kg
    2. Drug: ATYR1923 3 mg/kg
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of treatment-emergent adverse events (TEAEs)

    Time: Baseline through Day 60

    Secondary Outcomes

    Measure: Time to normalization of oxygen saturation (SpO2) (>93% on room air sustained for at least 24 hours)

    Time: Baseline through Day 14 or discharge

    Measure: Duration of supplemental oxygen (O2) requirement

    Time: Baseline through Day 14 or discharge

    Measure: Number of days with fever (temperature >100.4ºF [38.0ºC])

    Time: Baseline through Day 14 or discharge

    Measure: Time to normalization of temperature (≤100.4ºF [38.0ºC])

    Time: Baseline through Day 14 or discharge

    Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60

    Time: Baseline through Day 60

    Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score

    Time: Baseline through Day 60
    223 Phase II Study of Low Dose Pulmonary Irradiation in Patients With COVID-19 Infection of Bad Prognosis

    The administration of low-dose lung irradiation produces anti-inflammatory effects that will decrease the pulmonary inflammatory response. The present study will evaluate the efficacy of treatment with low-dose pulmonary radiotherapy added to standard support therapy, in hospitalized patients with respiratory symptoms due to COVID-19 pneumonia, who do not experience improvement with conventional medical therapy and are not subsidiaries of ICU

    NCT04414293
    Conditions
    1. COVID
    2. Pneumonia, Viral
    Interventions
    1. Radiation: Lung Low Dose Radiation
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical improvement of respiratory symptoms due to COVID-19 pneumonia after the treatment, measured as blood oxygen saturation levels

    Measure: blood oxygen saturation level

    Time: 48 hours

    Description: radiological improvement of respiratory symptoms due to COVID-19 pneumonia after the treatment.

    Measure: Torax X-ray

    Time: 48 hours

    Secondary Outcomes

    Description: number of days of hospital stay.

    Measure: Hospitalization

    Time: 2 months

    Description: Number of days free of assisted mechanical respiration.

    Measure: days free of assisted mechanical respiration

    Time: 3 month

    Description: number of deaths

    Measure: Mortality

    Time: 3 months
    224 Echocardiography in Critically-ill Patients With COVID-19 Pneumonia

    Critical care echocardiography (CCE) has been widely used since the 10 last years. Covid outbreak leads that many patients with acute respiratory failure were admitted in the ICU. Many of these patients were ventilated and developed ARDS. Some of them developed deep vein thrombosis and pulmonary embolism. Nothing is already described about the cardiac function and the hemodynamics in these patients (how many RV failure, LV systolic dysfunction,...). The echo group of the cardiodynamix section of European society of intensive care medicien (ESICM) aims to promote CCE and evaluate its interest. The objective is to retrospectively enter in an international database all the echo studies done as usual care in these patients to evaluate (i) incidence of RV failure, (ii) incidence of LV systolic function, (iii) incidence of other patterns. Another objective will be to look for any association between some patterns and respiratory strategy, blood gas analysis, systemic hemodynamics. The echo studies were done and will be reported following one of the recent systematic review published by the same group (Huang S et al. AOIC 2020).

    NCT04414410
    Conditions
    1. COVID
    2. Sars-CoV2
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: LV systolic dysfunction is defined as an ejection fraction < 45%

    Measure: Incidence of Left ventricular systolic dysfunction

    Time: Up to 28 days

    Description: RV failure is defined as RV/LV end-diastolic area > 0.8

    Measure: Incidence of RV failure

    Time: up to 28 days

    Description: Vasoplegia is defined as a normal or supranormal LV ejection fraction without echocarduiographic signs of hypovolemia.

    Measure: Incidence of Vasoplegia

    Time: Up to 28 days

    Description: Hypovolemia is defined as inspiratory collaspe of the superior vena cava in ventilated patients or virtual inferior vena cava in spontaneously breathing patients.

    Measure: Incidence of Hypovolemia

    Time: Up to 28 days

    Secondary Outcomes

    Description: Plateau pressure and RV size

    Measure: Relation between plateau pressure and RV failure

    Time: Up to 28 days

    Description: Tidal volume and RV size

    Measure: Relation between tidal volume and RV failure

    Time: Up to 28 days

    Description: PaO2, PaO2/FiO2, and RV size

    Measure: Relation between PaO2 and RV failure

    Time: Up to 28 days

    Description: PaCO2 and RV size

    Measure: Relation between PaCO2 and RV failure

    Time: Up to 28 days

    Description: PEEP and RV size

    Measure: Relation between PEEP and RV failure

    Time: Up to 28 days
    225 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia

    Opaganib, a sphingosine kinase-2 (SphK2) inhibitor, has been broadly tested in Phase I/II studies. Extensive nonclinical data indicates both anti-viral and anti-inflammatory activity via selective SphK2 inhibition which may prove beneficial for treating COVID-19 infection and resulting pneumonia. This proof of concept study will take place in the US and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. Half of the patients, i.e. 20 patients, will receive opaganib in addition to standard of care for 14 days. The other 20 will receive matching placebo (capsules that do not contain the medication) in addition to standard of care. Study drug will be administered every day for 14 days, twice each day, unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

    NCT04414618
    Conditions
    1. Coronavirus Infections
    Interventions
    1. Drug: Opaganib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Measurement of the oxygen requirement

    Measure: Evaluation of the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days

    Time: Every day from day 1 to day 14 of treatment

    Secondary Outcomes

    Description: Measurement of the oxygen requirement

    Measure: Evaluation of the time to 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min

    Time: Every day from day 1 to day 14 of treatment

    Measure: Evaluation of the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Measurement of temperature

    Measure: Evaluation of the proportion of afebrile patients at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Evaluation of the time to negative swabs for SARS-CoV-2 by PCR

    Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

    Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Evaluation of the proportion of patients with negative swabs for SARS-CoV-2 by PCR at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

    Measure: The percentage of patients who require intubation and mechanical ventilation by Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Measure: Evaluation of the time to mechanical ventilation

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Evaluation the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14

    Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Measure: Evaluation of mortality 30 days post-baseline

    Time: 30 days after day 1 of treatment

    Other Outcomes

    Measure: To determine the incidence rate of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Time: Every day from day 1 to day 14 of treatment and at end of the 4 weeks follow-up after the end of treatment
    226 the Determination of Extracellular Water (ECW) Which is Detected by Bioimpedence Method on Severe and Mild Covid 19 Pneumonia Clinical Course

    According to various studies Covid 19 pneumonia has a very similar clinical course to Acute Respiratory Distress Syndrome (ARDS) which has clarified by Berlin definition. Based on this similarity, extracellular fluid of lungs and diffuse alveolar damage should be observed in covid 19 pneumonia as well. Extracellular water (ECW) can be determine by using whole body bioimpedence system (NİCaS). The aim of this study is to investigate the effect of ECW on the clinical apperence of covid 19 pneumonia clinical course.

    NCT04416009
    Conditions
    1. Extracellular Fluid Alteration
    2. Corona Virus Infection
    Interventions
    1. Device: NİCaS
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Changes of three measurements of extracellular water in both lungs

    Measure: ECW

    Time: three measurements with half an hour intervals
    227 PREEMPTIVE THERAPY WITH COLCHICINE IN PATIENTS OLDER THAN 70 YEARS WITH HIGH RISK OF SEVERE PNEUMONIAE DUE TO CORONAVIRUS SARS-CoV2 (COVID-19)

    This is a phase 3 clinical trial, randomized, single-center, opened, controlled, to evaluate efficacy and safety of early administration of colchicines in patients older than 70 years, with high risk of pulmonary complications due to coronavirus SARS-CoV2 (COVID-19). An approximately number of 1000 subjects meeting all inclusion and none exclusion criteria will be randomized either to receive colchicines or symptomatic treatment with paracetamol during 21 days.

    NCT04416334
    Conditions
    1. SARS-CoV-2 Infection (COVID-19)
    Interventions
    1. Drug: Colchicine plus symptomatic treatment (paracetamol)
    2. Drug: Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations)
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of participants who die due to COVID-19 infection

    Time: 21 days post-randomization

    Measure: Number of participants who require hospitalization due to COVID-19 infection

    Time: 21 days post-randomization

    Other Outcomes

    Description: not delayed more than 48 hours from initial symptoms

    Measure: A confirmed diagnosis from COVID-19 infection (by positive PCR test) will be mandatory .

    Time: 48 hours
    228 Treatment Effect of Nafamostat Mesylate in Patients With COVID-19 Pneumonia: Open Labelled Randomized Controlled Clinical Trial

    In-vitro studies revealed that nafamostat mesylate has antiviral activity against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-inflammatory and anti-coagulation effect. However, there is no clinical studies on the efficacy of nafamostat in patients with COVID-19. This study is conducted to evaluate the clinical efficacy of nafamostate mesylate in adult patients hospitalized with COVID-19 pneumonia.

    NCT04418128
    Conditions
    1. Corona Virus Infection
    2. COVID-19
    Interventions
    1. Drug: Nafamostat Mesylate
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status. * Seven-category ordinal scale of clinical status not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death.

    Measure: Proportion of patients with clinical improvement

    Time: Day 14 & Day 28

    Secondary Outcomes

    Description: Time to clinical improvement (TTCI) was defined as time from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first.

    Measure: Time to clinical improvement (TTCI)

    Time: up to 28 days

    Description: * Seven-category ordinal scale of clinical status not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death. Higher scores of Seven-category ordinal scale mean serious clinical status.

    Measure: Clinical status assessed by 7-category ordinal scale

    Time: days 7, 14, and 28

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The range of NEW score is from zero to 23. Higher scores of NEWS mean the higher risk of poor outcomes. The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS)

    Time: Day 1 trough Day 28

    Measure: Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours

    Time: Day 1 through Day 28

    Measure: Duration of hospitalization

    Time: Day 1 through Day 28

    Measure: Duration of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 28

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 28

    Measure: Duration of new supplement oxygen use

    Time: Day 1 through Day 28

    Measure: Incidence of new supplement oxygen use

    Time: Day 1 through Day 28

    Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 28

    Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 28

    Measure: Mortality at day 28

    Time: Day 1 through Day 28

    Measure: Time (days) from treatment initiation to death

    Time: Day 1 through Day 28

    Measure: Proportions of patients with a negative nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR

    Time: days 3, 7, 10, 14, and 21

    Measure: Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR

    Time: days 3, 7, 10, 14, and 21

    Measure: Adverse events that occurred during treatment

    Time: Day 1 through Day 28
    229 A Pilot Study to Explore the Efficacy and Safety of Rescue Therapy With Antibodies From Convalescent Patients Obtained With Double-filtration Plasmapheresis (DFPP) and Infused in Patients With Coronavirus Disease 2019 (COVID-19) and Need of Oxygen Support Without Mechanical Ventilation

    The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Moreover, plasma-exchange is expensive and requires large volumes of substitution fluid With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The use of plasma as a substitution fluid further increases treatment costs and is associated with risk of infections, allergic reactions and citrate-induced hypocalcemia. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. The aforementioned limitations of plasma therapy can be in part overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP)3. During DFPP, plasma is separated from cellular components by a plasma filter, and is then allowed to pass through a fractionator filter. Depending on the membrane cut-off, the fractionator filter retains larger molecules and returns fluid along with smaller molecules to the circulation. Thus, the selection of a membrane with an appropriate sieving coefficient for IgG allows to efficiently clear autoantibodies in patients with antibody-mediated diseases (e.g., macroglobulinemia, myasthenia gravis and rheumatoid arthritis) with negligible fluid losses and limited removal of albumin and coagulation factors1. In patients with severe membranous nephropathy and high titer of autoreactive, nephritogenic antibodies against the podocyte-expressed M type phospholipase A2 receptor (PLA2R), DFPP accelerated anti PLA2R depletion4. Measurement of the antibody titer in treated patient and recovered fluid showed that antibody removal was extremely effective and that large part of antibodies was removed during the first DFPP procedure. This therapeutic regimen was safe and well tolerated and easy to apply4. In an ongoing pilot study we found that the same methodological approach can be used to remove circulating antibodies from patients who recovered from COVID 19 and to infuse these antibodies in patients with active viral infection. Treatment was well tolerated and preliminary findings are encouraging. Thus, in this novel pilot study we aim to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for patients with earlier stages of coronavirus (COVID-19) pneumonia requiring oxygen supply without mechanical ventilation.

    NCT04418531
    Conditions
    1. Pneumonia, Viral
    2. Corona Virus Infection
    Interventions
    1. Biological: Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time to weaning of oxygen support

    Time: Through study completion, an average of 3 months

    Secondary Outcomes

    Measure: Chest XR or CT scan evaluation

    Time: Changes during the study up completion, an average of 3 months

    Measure: Survival,

    Time: Through study completion, an average of 3 months

    Measure: Viral titer

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Measure: Anti COVID 19 IgG antibodies

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Measure: Anti COVID 19 IgM antibodies

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: C5a concentration

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: C3a concentration

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum C5b-9 concentration Marker of complement activation

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-6 levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-1b levels

    Time: Changes from before Ig administration, one day after Ig admini