CovidResearchTrials by Shray Alag


CovidResearchTrials Covid 19 Research using Clinical Trials (Home Page)


Report for D013577: Syndrome NIH

(Synonyms: Syndr, Syndro, Syndrom, Syndrome)

Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (144)


Name (Synonyms) Correlation
drug108 Azithromycin Wiki 0.23
drug83 Ascorbic Acid Wiki 0.20
drug978 Ruxolitinib Oral Tablet Wiki 0.19
drug255 ChAdOx1 MERS Wiki 0.19
drug698 Methylprednisolone Sodium Succinate Wiki 0.19
drug757 Nitric Oxide Gas Wiki 0.15
drug103 Awake Prone Positioning Wiki 0.13
drug807 Oxygen Therapy Wiki 0.13
drug118 BAT Wiki 0.13
drug1204 Umbilical Cord Mesenchymal Stem Cells Wiki 0.13
drug549 Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) Wiki 0.13
drug1264 allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC) Wiki 0.13
drug717 MuscleSound Ultrasound Wiki 0.13
drug166 Biospecimen collection Wiki 0.13
drug1149 Therapeutic Plasma Exchange Wiki 0.13
drug1223 Verapamil Wiki 0.13
drug859 Placebo for Azithromycin Wiki 0.13
drug606 Intravenous saline injection (Placebo) Wiki 0.13
drug607 Intravenous sedation Wiki 0.13
drug844 Physical Therapy Wiki 0.13
drug163 Biosensor Wiki 0.13
drug1126 Tele-medicine platform Wiki 0.13
drug445 Folic Acid Wiki 0.13
drug1401 standard procedure Wiki 0.13
drug617 Kerecis Oral and Nasal Spray Wiki 0.13
drug1005 Saline Nasal Irrigation Wiki 0.13
drug1035 Simvastatin Wiki 0.13
drug1224 Veru-111 Wiki 0.13
drug28 AMY-101 Wiki 0.13
drug774 Normal Saline Infusion + Maximal intensive care Wiki 0.13
drug195 CAStem Wiki 0.13
drug946 Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) Wiki 0.13
drug1087 Standards of Care Wiki 0.13
drug734 NaCl 0.9% Wiki 0.13
drug1118 TCM prescriptions Wiki 0.13
drug109 Azithromycin (Azithro) Wiki 0.13
drug148 Best Supportive Care Wiki 0.13
drug44 Airway pressure release ventilation Wiki 0.13
drug58 Amiodarone Wiki 0.13
drug1170 Tocilizumab 180 MG/ML Wiki 0.13
drug1373 placebo Wiki 0.13
drug860 Placebo for Hydroxychloroquine Wiki 0.13
drug600 Intervention program Wiki 0.13
drug831 Pectin Wiki 0.13
drug48 Allogeneic NK transfer Wiki 0.13
drug917 Q-NRG Metobolic Cart Device Wiki 0.13
drug119 BAT + Calcifediol Wiki 0.13
drug126 BLD-2660 Wiki 0.13
drug712 MultiStem Wiki 0.13
drug582 Inhaled sedation Wiki 0.13
drug1205 Umbilical cord Wharton's jelly-derived human Wiki 0.13
drug158 Biological sampling Wiki 0.13
drug615 Ivermectine Wiki 0.13
drug105 Ayurveda Wiki 0.13
drug137 Bacille Calmette-Guérin (BCG) Wiki 0.13
drug135 BVRS-GamVac Wiki 0.13
drug716 Muscle ultrasound Wiki 0.13
drug812 PEEP trial Wiki 0.13
drug851 Placebo (Plasma-Lyte 148) Wiki 0.13
drug1236 WFI 5% glucose Wiki 0.13
drug1206 Umifenovir Wiki 0.13
drug1207 Unfractionated heparin Wiki 0.13
drug159 Biological test Wiki 0.13
drug364 Dexamethasone and Hydroxychloroquine Wiki 0.13
drug107 Azinc Wiki 0.13
drug121 BCG GROUP Wiki 0.13
drug1302 eculizumab Wiki 0.13
drug591 Interferon-β 1a Wiki 0.13
drug102 Aviptadil by intravenous infusion + maximal intensive care Wiki 0.13
drug1093 Streptokinase Wiki 0.13
drug1247 XCEL-UMC-BETA Wiki 0.13
drug737 Naltrexone Wiki 0.13
drug500 Human umbilical cord derived CD362 enriched MSCs Wiki 0.13
drug1312 hospitalized children with Covid19 Wiki 0.13
drug458 Gimsilumab Wiki 0.13
drug1244 Wharton's jelly derived Mesenchymal stem cells. Wiki 0.13
drug52 Alteplase 100 MG [Activase] Wiki 0.13
drug718 N-803 Wiki 0.13
drug639 Lopinavir / Ritonavir plus Ribavirin Wiki 0.13
drug945 Ravulizumab Wiki 0.13
drug1055 Standard Mask Wiki 0.13
drug366 Dexmedetomidine Injectable Product Wiki 0.13
drug15 2: No instruction regarding positioning Wiki 0.13
drug614 Ivermectin plus Nitazoxanide Wiki 0.13
drug263 Chloroquine Diphosphate Wiki 0.13
drug618 Ketamine Wiki 0.13
drug266 Chloroquine diphosphate Wiki 0.13
drug1219 Valsartan (Diovan) Wiki 0.13
drug85 Aspirin Wiki 0.13
drug302 Continuous renal replacement therapy Wiki 0.13
drug53 Alteplase 50 MG [Activase] Wiki 0.13
drug1307 gammaCore® Sapphire (non-invasive vagus nerve stimulator) Wiki 0.13
drug855 Placebo Comparator Wiki 0.13
drug114 Azithromycin Capsule Wiki 0.13
drug867 Placebo solution Wiki 0.13
drug1070 Standard of care therapies Wiki 0.13
drug1089 Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki 0.13
drug1007 Saline with Baby Shampoo Nasal Irrigation Wiki 0.13
drug136 BVRS-GamVac-Combi Wiki 0.13
drug36 Acacia Senegal Wiki 0.13
drug814 PLACEBO GROUP Wiki 0.13
drug928 Questionnaires for specific phobia Wiki 0.13
drug42 Aerosol-reducing Mask Wiki 0.13
drug713 Multifrequency Bioimpedance Spectroscopy Wiki 0.13
drug11 1: Prone positioning Wiki 0.13
drug111 Azithromycin 500 mg Wiki 0.13
drug505 Hydroxychloroquine Wiki 0.13
drug522 Hydroxychloroquine Sulfate Wiki 0.12
drug977 Ruxolitinib Wiki 0.10
drug499 Human immunoglobulin Wiki 0.09
drug379 Doxycycline Wiki 0.09
drug839 Peripheral blood draw Wiki 0.09
drug534 Hydroxychloroquine and Azithromycin Wiki 0.09
drug1135 Telmisartan Wiki 0.09
drug1397 standard care Wiki 0.09
drug905 Prone positioning Wiki 0.09
drug959 Remestemcel-L Wiki 0.09
drug378 Dornase Alfa Inhalation Solution [Pulmozyme] Wiki 0.09
drug1258 Zinc Sulfate Wiki 0.09
drug833 Peginterferon Lambda-1A Wiki 0.09
drug1052 Standard Care Wiki 0.09
drug1036 Single Dose of Hydroxychloroquine Wiki 0.09
drug850 Placebo Wiki 0.08
drug122 BCG Vaccine Wiki 0.08
drug637 Lopinavir / Ritonavir Wiki 0.08
drug506 Hydroxychloroquine (HCQ) Wiki 0.08
drug212 COVID-19 RT-PCR Wiki 0.08
drug1291 convalescent plasma Wiki 0.08
drug694 Mesenchymal Stromal Cells Wiki 0.08
drug1133 Telerehabilitation Wiki 0.07
drug1211 Usual Care Wiki 0.07
drug1280 blood sampling Wiki 0.07
drug662 Lung ultrasound Wiki 0.07
drug1003 Saline Wiki 0.07
drug1168 Tocilizumab Wiki 0.06
drug1060 Standard care Wiki 0.06
drug318 Convalescent plasma Wiki 0.05
drug865 Placebo oral tablet Wiki 0.05
drug1012 Sarilumab Wiki 0.05
drug650 Losartan Wiki 0.05
drug697 Methylprednisolone Wiki 0.04
drug1062 Standard of Care Wiki 0.04
drug1067 Standard of care Wiki 0.04
drug872 Placebos Wiki 0.03

Correlated MeSH Terms (30)


Name (Synonyms) Correlation
D012127 Respiratory Distress Syndrome, Newborn NIH 0.52
D055371 Acute Lung Injury NIH 0.50
D012128 Respiratory Distress Syndrome, Adult NIH 0.47
D045169 Severe Acute Respiratory Syndrome NIH 0.21
D018352 Coronavirus Infections NIH 0.19
D055370 Lung Injury NIH 0.17
D011665 Pulmonary Valve Insufficiency NIH 0.13
D059350 Chronic Pain NIH 0.13
D054143 Heart Failure, Systolic NIH 0.13
D000787 Angina Pectoris NIH 0.13
D012818 Signs and Symptoms, Respiratory NIH 0.13
D000071257 Emergence Delirium NIH 0.13
D054058 Acute Coronary Syndrome NIH 0.09
D003693 Delirium NIH 0.09
D003327 Coronary Disease NIH 0.09
D011014 Pneumonia NIH 0.09
D007249 Inflammation NIH 0.08
D006333 Heart Failure NIH 0.08
D018746 Systemic Inflammatory Response Syndrome NIH 0.08
D003324 Coronary Artery Disease NIH 0.08
D009102 Multiple Organ Failure NIH 0.08
D009203 Myocardial Ischemia NIH 0.07
D011024 Pneumonia, Viral NIH 0.06
D008171 Lung Diseases, NIH 0.05
D058186 Acute Kidney Injury NIH 0.05
D007251 Influenza, Human NIH 0.05
D014947 Wounds and Injuries NIH 0.04
D002318 Cardiovascular Diseases NIH 0.03
D007239 Infection NIH 0.02
D014777 Virus Diseases NIH 0.02

Correlated HPO Terms (10)


Name (Synonyms) Correlation
HP:0001681 Angina pectoris HPO 0.13
HP:0012532 Chronic pain HPO 0.13
HP:0010444 Pulmonary insufficiency HPO 0.13
HP:0002090 Pneumonia HPO 0.09
HP:0001677 Coronary artery atherosclerosis HPO 0.08
HP:0001635 Congestive heart failure HPO 0.08
HP:0001658 Myocardial infarction HPO 0.07
HP:0002088 Abnormal lung morphology HPO 0.05
HP:0001919 Acute kidney injury HPO 0.05
HP:0001626 Abnormality of the cardiovascular system HPO 0.03

There are 57 clinical trials

Clinical Trials


1 Clinical Evaluation and Management of Persons With Severe Acute Respiratory Syndrome (SARS)

This study will evaluate and treat people with SARS, a new type of pneumonia (lung infection) originating in China. SARS is caused by a new virus that is easily transmitted from person to person. This study will look at the course of the disease; determine how the virus affects the body and how the body fights the infection; and evaluate diagnostic tests to quickly identify the disease. People 18 years of age and older with probable or suspected SARS may be eligible for this study. Close contacts of patients with SARS, patients who recovered from SARS, and NIH health care workers involved in the care of patients will also be enrolled. Patients with SARS who require hospitalization will be admitted to the NIH Clinical Center. Because SARS spreads easily, hospitalized patients will be in a room by themselves and will not be allowed any visitors. They will not leave their room except for tests, such as x-rays. All participants will have a full medical examination, including a medical history, physical examination, and blood tests. In addition, the participants undergo various tests and procedures as follows: - Probable and suspected SARS patients may be hospitalized or may be seen as outpatients. They are provided the treatment judged best for their disease, usually according to expressed or published recommendations. The best treatment for SARS is not yet known, and there have been no studies evaluating therapies. Outpatients are seen three times a week for 2 weeks, once a week for 4 more weeks, and then at 6 months. Patients have mouth and throat swabs taken three times a week for the first 2 weeks, then once a week for 4 more weeks. Blood is drawn three times a week for the first 2 weeks, then once at weeks 3, 4, and 6. If virus is still detectable after 6 weeks, nose washings and throat swabs are repeated until no virus is detected for 3 weeks in a row. In addition, patients provide urine and stool samples, have a chest x-ray and electrocardiogram, and undergo bronchoscopy and bronchial lavage. For the bronchoscopy, a bronchoscope (pencil-thin flexible tube) is passed into the large airways of the lung, allowing the physician to examine the airways. Cells and secretions from the airways are rinsed from the lung with salt water. A brush the size of a pencil tip is passed through the bronchoscope to scrape cells lining the airways and pieces of tissue are collected for analysis. - Close contacts of patients are evaluated twice a week for 2 weeks, then once a week for 2 more weeks. Blood is drawn at the first visit and then at 1, 2, and 4 weeks. Mouth and throat swabs, nose washings, and sputum collections are done twice a week for 2 weeks, then once a week for 2 more weeks. Urine and stool samples are collected once a week for 4 weeks. If virus from the nose or throat is still detectable after 4 weeks, weekly nose washings and throat swabs continue until no virus is detected for 3 weeks in a row. Blood may also be drawn during the weekly visits. - Recovered SARS patients provide blood, urine, and stool samples and have a mouth and throat swab and nose aspiration to see if the SARS virus is present. For the nasal aspiration, salt water is put in the nose and then suctioned out. Usually, these tests are done only once. If virus is detected, however, the nose washing, throat swabs and blood tests are repeated once a week until no virus is detected for 3 weeks in a row. - Health care workers document their contact with patients, use of isolation procedures and equipment, and any unexpected events that occur during contact. They are evaluated for symptoms of infection and provide a blood sample once a month

NCT00073086 Severe Acute Respiratory Syndrome
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome


2 The Interaction Between Severe Acute Respiratory Distress Syndrome Viral Proteins and Monocytes

Severe acute respiratory syndrome (SARS) is a new threat to public health since November, 2002. The SARS is highly contagious and is believed to be transmitted by person-to-person through droplet and direct contact. The patients present with fever, chills, cough, myalgia, dyspnea, and diarrhea. The symptoms aggravate in the second week and nearly 40% of the patients develop respiratory failure that requires assisted ventilation. The mortality rate is reported as 6.5%-7%. After several months, the world scientists found the etiology to be a new coronavirus not belonging to the previous coronavirus group I, II and III. The new virus is called SARS associated coronavirus (SARS-CoV). Although the high morbidity and mortality of SARS occurred in adults, there was rare mortality reported in the children. The report from Hong Kong pointed out that the symptoms of SARS in younger children were milder and the clinical course was not as aggressive as in adults. Therefore, the aim of the project is to design the experiment to see the differences of immunological responses to SARS-CoV protein in healthy younger children, teenagers, and adults. The investigators hope that the result could explain the reason for milder disease in younger children and the immunological pathogenesis of SARS.

NCT00172263 Severe Acute Respiratory Syndrome Procedure: blood sampling
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome


3 A Multi-centre, Double-blinded, Randomized, Placebo-controlled Trial on the Efficacy and Safety of Lopinavir / Ritonavir Plus Ribavirin in the Treatment of Severe Acute Respiratory Syndrome

The study aims to examine whether the combination of Lopinavir/Ritonavir plus Ribavirin for treatment of severe acute respiratory syndrome (SARS) is superior to placebo.

NCT00578825 Severe Acute Respiratory Syndrome Drug: Lopinavir / Ritonavir plus Ribavirin
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

Primary Outcomes

Measure: Development of severe SARS

Time: Any time during the acute illness

Secondary Outcomes

Measure: Adverse events

Time: Throughout the illness period

Measure: SARS-CoV Viral load

Time: Throughout the illness period

Measure: Immunological profile

Time: Throughout the illness period

4 An International Observational Study to Characterize Adults Who Are Hospitalized With Influenza or Other Targeted Respiratory Viruses

Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to estimate rates of morbidity and mortality and to examine predictors of severity among participants with 2009 H1N1 infection. In 2011, as surveillance indicated that 2009 H1N1 virus was co-circulating with other seasonal influenza A and B viruses worldwide, the protocol was expanded to include other influenza A subtypes and influenza B viruses. The current version of the protocol (released in August 2013) further broadens the scope of this observational study. With the recognition that novel respiratory viruses other than novel influenza A viruses, e.g., Middle East Respiratory Syndrome Coronavirus (MERS-CoV), could become prevalent and of major public health importance, the objectives of this protocol have been expanded.

NCT01056185 Influenza Novel Respiratory Virus-1 Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) Novel Respiratory Virus-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
MeSH:Influenza, Human Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome Virus Diseases

Primary Outcomes

Measure: Death

Time: 60-day period following enrollment

Secondary Outcomes

Measure: Recovery from influenza illness (including days lost from normal activities) duration of hospitalization, days in intensive care, days of mechanical ventilation, days of dialysis, pregnancy outcome

Time: approximately 60 days

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

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

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

Primary Outcomes

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

Measure: Oxygenation index (OI)

Time: Day 7

Description: Incidence of SAEs

Measure: Incidence of Serious Adverse Events (SAEs)

Time: 28 days

Secondary Outcomes

Measure: Oxygenation index

Time: Days 4 and 14

Description: SOFA score is a measure of organ failure

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: Days 4, 7 and 14

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

Measure: Respiratory compliance (Crs)

Time: Days 4, 7 and 14

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

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

Time: Days 4, 7 and 14

Measure: Driving Pressure

Time: Days 4, 7 and 14

Measure: Extubation and reintubation

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

Measure: Ventilation free days at day 28

Time: Day 28

Measure: Length of ICU and hospital stay

Time: Until the patient is discharged or the patient dies

Measure: 28-day and 90-day mortality

Time: Up to 28 and 90 days

6 Implementation of Lung Protective Ventilation in Patients With Acute Respiratory Failure

This is a quality improvement study with the purpose of observing and measuring the effects of implementation of a proven standardized lung protective ventilation protocol in the new electronic medical record system iCentra across all Intermountain Healthcare hospitals. Approximately 14,000 records will be accessed for this study from a database of mechanically ventilated patients established for quality improvement purposes. The investigators hypothesize that implementation of a standardized computerized lung protective ventilation protocol across all Intermountain Healthcare hospitals will be feasible, will decrease initial tidal volumes to the target 6 ml/kg PBW, and will improve outcomes. The objectives of this study are to: - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in patients with acute respiratory failure requiring mechanical ventilation - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in the sub-group of patients with the acute respiratory distress syndrome (ARDS) - Measure compliance with the implementation of a computerized lung protective ventilation protocol at 12 Intermountain Healthcare hospitals

NCT03225807 Acute Respiratory Distress Syndrome ARDS Respiratory Distress Syndrome, Acute Respiratory Insufficiency Respiratory Distress Syndrome Shock Lung Severe Acute Respiratory Syndrome
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Pulmonary Valve Insufficiency Syndrome
HPO:Pulmonary insufficiency

Primary Outcomes

Measure: Ventilator free days to day 28

Time: 28 days

Secondary Outcomes

Measure: 30 day mortality

Time: 30 days

Measure: 90 day mortality

Time: 90 days

Measure: Hospital discharge disposition

Time: 30 days

Measure: Hospital mortality

Time: 1 week

Measure: Time to first ICU activity

Time: 24 hours

7 A Phase I Study to Determine the Safety and Immunogenicity of the Candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Vaccine ChAdOx1 MERS in UK Healthy Adult Volunteers

This is a clinical trial in which healthy volunteers will be administered an experimental MERS vaccine. The vaccine ChAdOx1 MERS will be administered alone both as a single administration and with a homologous prime-booster.

NCT03399578 MERS (Middle East Respiratory Syndrome) Biological: ChAdOx1 MERS
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration

Measure: Occurrence of solicited and unsolicited local and systemic adverse events

Time: up to 28 days following vaccination

Secondary Outcomes

Description: ELISA to quantify antibodies to MERS Spike protein antigen Ex vivo ELISpot responses to MERS Spike protein antigen

Measure: Measures of immunogenicity to the ChAdOx1 MERS vaccine

Time: 12 months

8 Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Partially Randomized Controlled Trial

Background: Intra-alveolar clotting and alveolar collapse in ARDS is due to alveolar capillaries epithelial and leakage. Subsequently, collapse induces hypoxemia that is resistant to recruitment (RM). Heparin and Streptokinase may prevent or dissolve intra-alveolar fibrin clot respectively helping alveolar re-expansion. We examined and compared the effect of nebulizing Heparin versus Streptokinase on reversing this pathology. Methods: Sixty severe ARDS (PaO2/FiO2<100) patients and failure of RM, prone position (PP) and neuromuscular block (NMB) were partially randomised into Group (I): (n=20) received nebulized Heparin 10000 IU/4h. Group (II): (n=20) received nebulized Streptokinase 250,000 IU/4h. Group (III): (n=20) received conservative management. Randomization to either Heparin or Streptokinase groups was applied to patients whom guardian accepted participation, while those who declined participation were followed-up as a control. The primary outcome was the change in PaO2/FiO2; the secondary outcomes included the change in compliance, plateau pressure, ventilation-off days, coagulation and ICU mortality.

NCT03465085 Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome Drug: Unfractionated heparin Drug: Streptokinase
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Change in the ratio of arterial oxygen tension to fraction of inspired oxygen from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

Measure: Change in PaO2/FiO2 ratio

Time: daily over eight days

Secondary Outcomes

Description: Change in the plateau airway pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

Measure: Change in the plateau pressure

Time: daily over eight days

Description: change in volume of the lungs per change in pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

Measure: Change in the pulmonary compliance

Time: daily over eight days

Description: Number of patients who are discharged alive

Measure: ICU survival rate

Time: At the end of ICU stay up to one year after the start of recruitment

Description: the total duration the patient stays in ICU

Measure: ICU length of stay

Time: At the end of ICU stay up to one year after the start of recruitment

Description: number of patients who required tracheostomy

Measure: Tracheostomy rate

Time: During ICU stay up to one month after the start of recruitment

9 Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug "BVRS-GamVac-Combi", a Combined Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of heterologous adenoviral-based vaccine against MERS - BVRS-GamVac-Combi.

NCT04128059 MERS (Middle East Respiratory Syndrome) MERS Drug: BVRS-GamVac-Combi Other: placebo
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: Determination of Number of Participants With Adverse Events

Measure: Number of Participants With Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants With Serious Adverse Events

Measure: Number of Participants With Serious Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants with Solicited Local and Systemic Adverse Events

Measure: Number of Participants with Solicited Local and Systemic Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2)

Measure: Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA)

Time: Time Frame for group 1 phase 1: at days 0, 7, 14, 21, 28, 42, 56 and 90. Time Frame for group 2 phase 1 and phase 2: at days 0, 7, 14, 21, 28, 35, 42, 56 and 90

Secondary Outcomes

Description: determination of specific T-cell- mediated response vs. baseline values and placebo

Measure: Assessment of antigen-specific cell-mediated immune response

Time: at 0, 14 and 28 days from the start of vaccination compared to baseline values (phase 1, phase 2) and placebo (phase 2)

Description: Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values and placebo

Measure: Neutralizing antibody levels

Time: at days 0, 14 and 28 from the start of vaccination compared to baseline values

10 Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug "BVRS-GamVac", a Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of adenoviral-based vaccine against MERS - BVRS-GamVac.

NCT04130594 MERS (Middle East Respiratory Syndrome) MERS Biological: BVRS-GamVac Other: placebo
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: Determination of Number of Participants With Adverse Events

Measure: Number of Participants With Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants With Serious Adverse Events

Measure: Number of Participants With Serious Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of Number of Participants with Solicited Local and Systemic Adverse Events

Measure: Number of Participants with Solicited Local and Systemic Adverse Events

Time: through the whole study, an average of 180 days

Description: Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2)

Measure: Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA)

Time: at days 0, 7, 14, 21, 28, 42, 56 and 90

Secondary Outcomes

Description: determination of specific T-cell- mediated response vs. baseline values (phase 1, phase 2) and placebo (phase 2)

Measure: Assessment of antigen-specific cell-mediated immune response

Time: at 0 and 14 days from the start of vaccination compared to baseline values (day 0)

Description: Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values

Measure: Neutralizing antibody levels

Time: at days 0, 14 and 28

11 A Phase Ib Study to Determine the Safety and Immunogenicity of the Candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Vaccine ChAdOx1 MERS in Healthy Adult Middle Eastern Volunteers

A phase Ib study to determine the safety and immunogenicity of the candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine ChAdOx1 MERS in healthy adult Middle Eastern volunteers

NCT04170829 Middle East Respiratory Syndrome Coronavirus Biological: ChAdOx1 MERS
MeSH:Coronavirus Infections Syndrome

Primary Outcomes

Description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration

Measure: Occurrence of solicited and unsolicited local and systemic adverse events

Time: 28 days following the vaccination

Secondary Outcomes

Description: ELISA to quantify antibodies to MERS Spike protein antigen Ex vivo ELISpot responses to MERS Spike protein antigen

Measure: Measures of immunogenicity to the ChAdOx1 MERS vaccine

Time: 6.5 months following completion of the vaccination regimen

12 Nitric Oxide Gas Inhalation Therapy for Severe Acute Respiratory Syndrome Due to COVID-19.

The investigators will enroll 102 patients with a confirmed diagnosis of COVID-19. Patients will be randomized to receive either inhaled nitric oxide (per protocol) or placebo. ICU Standards of care will be the institution's own protocols (such as ventilation strategies and use and dose of antivirals and antimicrobials, steroids, inotropic and vasopressor agents).

NCT04290871 Coronavirus SARS (Severe Acute Respiratory Syndrome) Drug: Nitric Oxide Gas
MeSH:Coronavirus Infe Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Percentage of patients that have a PaO2/FiO2 ratio steadily > 300 in ambient air

Measure: SARS-free patients at 14 days

Time: 14 days since beginning of treatment

Secondary Outcomes

Measure: Survival at 28 days

Time: 28 days

Measure: Survival at 90 days

Time: 90 days

Description: Composite outcome in which: Death=0, Days of treatment =1

Measure: SARS-free days at 28 days

Time: 28 days

Description: Composite outcome in which: Death=0, Days of treatment =1

Measure: SARS -free days at 90 days

Time: 90 days

Description: Incidence

Measure: Renal Replacement Therapy

Time: 28 days

Description: Incidence

Measure: Liver Failure

Time: 28 days

Description: Incidence of patients requiring VA-ECMO, LVAD, IABP

Measure: Mechanical Support of Circulation

Time: 28 days

Description: In ambient air if possible

Measure: PaO2/FiO2 ratio in ambient air

Time: daily for 28 days

13 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 Severe Acute Respiratory Syndrome (SARS) Pneumonia 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

14 Nitric Oxide Gas Inhalation Therapy for Mechanically Ventilated Patients With Severe Acute Respiratory Syndrome Caused by SARS-CoV2: a Randomized Clinical Trial.

Severe acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation

NCT04306393 SARS (Severe Acute Respiratory Syndrome) Coronavirus Drug: Nitric Oxide Gas
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Difference within groups in terms of PaO2/FiO2 ratio. If a patient dies during the first 48 hours of treatment, the last available blood gas analysis will be used.

Measure: Change of arterial oxygenation at 48 hours from enrollment

Time: 48 hours

Secondary Outcomes

Description: Time to recover gas exchange to a PaO2/FiO2 =/> 300 for at least 24 hours during the first 28 days after enrollment, within each group and comparison between groups. If the patient dies before day 28, the patient will be considered as "never recovered".

Measure: Time to reach normoxemia during the first 28 days after enrollment

Time: 28 days

Description: Daily proportion of patients with a PaO2/FiO2 ratio > 300 for at least 24 hours within each group and comparison between groups. If a patient dies before day 28, the patient will be considered as "never recovered".

Measure: Proportion of SARS-nCoV-2 free patients during the first 28 days after enrollment

Time: 28 days

Description: Proportion of patients surviving at 28 days within each group and comparison between groups.

Measure: Survival at 28 days from enrollment

Time: 28 days

Description: Proportion of patients surviving at 90 days within each group and comparison between groups.

Measure: Survival at 90 days from enrollment

Time: 90 days

Other Outcomes

Description: Expressed as PaO2/FiO2 ratio within each group and comparison between groups.

Measure: Daily oxygenation in the two groups until day 28

Time: 28 days

Description: Proportion of patients needing RRT within each group and comparison between groups.

Measure: Need for new renal replacement therapy during the first 28 days

Time: 28 days

Description: Proportion of patients needing (i.e., ECMO, intra-aortic balloon pump, VADs) within each group and comparison between groups.

Measure: Mechanical support of circulation during the first 28 days

Time: 28 days

Description: Average days without need for vasopressors within each group and comparison between groups.

Measure: Days free of vasopressors during the first 28 days

Time: 28 days

Description: Average days without need for mechanical ventilation within each group and comparison between groups.

Measure: Ventilator-free day at 28 days

Time: 28 days

Description: Time to obtain first negative upper respiratory trait sample in the 2019-nCoV rt-PCR assay. Average within groups and comparison between groups.

Measure: Time to SARS-CoV-2 rt-PCR negative in upper respiratory tract specimen

Time: 28 days

Description: Average days out of ICU within each group and comparison between groups.

Measure: ICU-free days at 28 days

Time: 28 days

Description: Average days of ICU admission within each group and comparison between groups.

Measure: ICU length of stay

Time: 90 days

15 Clinical Trial on Regularity of TCM Syndrome and Differentiation Treatment of COVID-19 in Jiangsu Province

Evaluation of the efficacy and safety of TCM differential treatment of COVID-19 in Jiangsu Province based on a prospective multicenter cohort study.

NCT04306497 COVID-19 Drug: TCM prescriptions
MeSH:Syndrome

Primary Outcomes

Description: disappearance of fever, cough and shortness of breath/ the rate of complete relief /.

Measure: The relief / disappearance rate of main symptoms

Time: 9day

Description: with reference to the "pneumonia chest X-ray absorption Evaluation scale" developed by Renyi Yin et al, the final absorption judgment will be used to evaluate the chest CT absorption of patients with pneumonia, which is divided into four levels according to the degree of absorption: complete absorption, majority absorption, partial absorption and no absorption.

Measure: Chest CT absorption

Time: 9day

Secondary Outcomes

Description: detection negative rat of nasopharyngeal swab, conjunctival sac secretion virus nucleic acid e

Measure: Virus antigen negative conversion rate

Time: 9day

Description: the average time it takes for the clinical curative effect to reach the effective standard. Median response time: the average time it takes for 50% of patients to reach the effective standard.

Measure: Clinical effective time: the average effective time

Time: 9day

Description: the number of severe and critical cases occurred after the start of intervention.

Measure: The number of severe and critical conversion cases

Time: 9day

Description: defined as complications during isolation and hospitalization due to pneumonia infected by novel coronavirus, including bacterial infection, aggravation of underlying diseases, etc

Measure: Incidence of complications

Time: 9day

Description: According to the Traditional Chinese Medicine symptom score scale, the change of symptom score before and after treatment was observed.The highest score was 92 points, and the lowest was 23 points. The higher the score, the more severe the symptoms.

Measure: Traditional Chinese Medicine Syndrome Score

Time: 9day

Other Outcomes

Description: Changes in c-reactive protein.

Measure: CRP changes

Time: 9day

Description: Changes in erythrocyte sedimentation rate.

Measure: ESR changes

Time: 9day

Description: Changes in procalcitonin.

Measure: PCTchanges

Time: 9day

Description: Changes of CD4+ and CD8+

Measure: The index of T cell subsets changed

Time: 9day

16 A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19

Some patients infected with the COVID-19 can develop uncontrolled immune response, leading to potentially life-threatening damage to lung tissue. Tocilizumab was first approved by the U.S. FDA in 2010 for rheumatoid arthritis and might now be used to treat serious COVID-19 patients with lung damage, according to China's National Health Commission updated its treatment guidelines in 7th version.Continuous Renal Replacement Therapy (CRRT) was recommended by China's National Health Commission treatment guidelines in 1st-7th version to control sever COVID-19 patients.

NCT04306705 Covid-19 SARS Cytokine Storm Cytokine Release Syndrome Tocilizumab Drug: Tocilizumab Other: Standard of care Procedure: Continuous renal replacement therapy
MeSH:Syndrome

Primary Outcomes

Description: This is a composite outcome measure. Criteria for fever normalization: Temperature < 36.6 °C armpit, < 37.2 °C oral sustained for at least 72 hours and criteria for oxygen normalization: peripheral capillary oxygen saturation (Sp02) > 94% sustained for at least 72 hours.

Measure: Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14

Time: First dose date up to 14 days

Secondary Outcomes

Description: Measured in days

Measure: Duration of hospitalization

Time: Up to 28 days

Description: Criteria for: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for at least 72 hours.

Measure: Proportion of Participants With Normalization of Fever Through Day 14

Time: First dose date up to 14 days

Description: Blood routine test

Measure: Change from baseline in white blood cell and differential count

Time: Day 1 through Day 28

Description: Oropharyngeal or anal swabs

Measure: Time to first negative in 2019 novel Corona virus RT-PCR test

Time: Up to 28 days

Description: Date and cause of death (if applicable).

Measure: All-cause mortality

Time: up to 12 weeks

Description: Serum hsCRP

Measure: Change from baseline in hsCRP

Time: Day 1 through Day 28

Description: Serum inflammatory cytokines

Measure: Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α

Time: Day 1 through Day 28

Description: Flow cytometry for peripheral whole blood

Measure: Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells

Time: Day 1 through Day 28 (if applicable)

17 Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress

Novel Corona Virus (COVID-19) is known to cause Acute Lung Injury/Acute Respiratory Distress Syndrome, that results in death of approximately 80% of those who develop ARDS, despite intensive care and mechanical ventilation. Patients with COVID-19 induced Acute Respiratory Distress Syndrome who are admitted for intensive care including endotracheal intubation and mechanical ventilation will be treated with Aviptadil, a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.

NCT04311697 Acute Respiratory Distress Syndrome Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Corona Virus Infection Drug: Aviptadil by intravenous infusion + maximal intensive care Drug: Normal Saline Infusion + Maximal intensive care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome

Primary Outcomes

Description: Mortality

Measure: Mortality

Time: 5 Days with followup through 30 days

Description: Index of Respiratory Distress

Measure: PaO2:FiO2 ratio

Time: 5 Days with followup through the end of telemetry monitoring

Secondary Outcomes

Description: TNF alpha levels as measured in hospital laboratory

Measure: TNF alpha

Time: 5 Days

Description: Multi-system organ failure free days

Measure: Multi-system organ failure free days

Time: 5 days with followup through 30 days

18 Uppsala Intensive Care Study of Mechanisms for Organ Dysfunction in Covid-19

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

NCT04316884 COVID-19 Organ Dysfunction Syndrome Sepsis Organ Dysfunction Syndrome, Multiple Septic Shock Acute Kidney Injury Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Acute Kidney Injury Syndrome Multiple Organ Failure Systemic Inf Systemic Inflammatory Response Syndrome
HPO:Acute kidney injury

Primary Outcomes

Description: KDIGO AKI score

Measure: Acute Kidney Injury

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

Secondary Outcomes

Description: Acute Respiratory Distress Syndrome yes/no

Measure: ARDS

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

Description: Death within 30 days of ICU admission

Measure: 30 day mortality

Time: 30 days

Description: Death within 1 year of ICU admission

Measure: 1 year mortality

Time: 1 year

Description: Development of Chronic Kidney Disease

Measure: Chronic Kidney Disease

Time: 60 days and 1 year after ICU admission

Description: Sequential Organ Failure Score as a continuous variable

Measure: SOFA-score

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

19 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 SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia 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

20 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. We're routinely using MP for severe pneumonia-ARDS with acute respiratory failure with very good results. The main objective of this multi-centre observational trial is to evaluate the efficacy of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome.

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

Primary Outcomes

Description: Death or ICU admission or Invasive mechanical ventilation (yes/not, at least one of three of the composite end-point)

Measure: Composite primary end-point

Time: 28 days

Description: Yes/no

Measure: death

Time: 28 days

Description: yes/no

Measure: Admission to ICU

Time: 28 days

Description: yes/no

Measure: Endotracheal intubation (invasive mechanical ventilation)

Time: 28 days

Secondary Outcomes

Description: mg/L

Measure: reduction of C-reactive protein or CRP

Time: 14 days and 28 days

Description: number of days free from mechanical ventilation (invasive or not)

Measure: Reduction of mechanical ventilation

Time: 28 days

21 Integrated Distance Management Strategy for Patients With Cardiovascular Disease (Ischaemic Coronary Artery Disease, High Blood Pressure, Heart Failure) in the Context of the COVID-19 Pandemic

Management of known patients with cardiovascular disease (in particular the whole spectrum of atherosclerotic ischaemic coronary artery disease, essential hypertension under treatment, and also patients with chronic heart failure under medication) and with other associated chronic pathologies, with obvious effects on the management of the pandemic with modern / distance means (e-Health) of patients at high risk of mortality in contact with coronavirus. Given the Covid-19 Pandemic, all the above complex cardiovascular patients are under the obligation to stay in the house isolated and can no longer come to standard clinical and paraclinical monitoring and control visits. Therefore, a remote management solution (tele-medicine) of these patients must be found. The Investigators endeavour is to create an electronic platform to communicate with these patients and offer solutions for their cardiovascular health issues (including psychological and religious problems due to isolation). The Investigators intend to create this platform for communicating with a patient and stratify their complaints in risk levels. A given specialist will sort and classify their needs on a scale, based on specific algorithms (derived from the clinical European Cardiovascular Guidelines), and generate specific protocols varying from 911 like emergencies to cardiological advices or psychological sessions. These could include medication changing of doses, dietary advices or exercise restrictions. Moreover, in those patients suspected of COVID infection, special assistance should be provided per protocol.

NCT04325867 Angina Pectoris Acute Coronary Syndrome Coronary Syndrome Coronary Artery Disease Angioplasty Stent Restenosis Hypertension Heart Failure, Systolic Depression, Anxiety Covid-19 Isolation, Social Other: Tele-medicine platform
MeSH:Heart Failure Coronary Artery Disease Myocardial Ischemia Coronary Disease Acute Coronary Syndrome Angina Pectoris Heart Failure, Systolic Syndrome Cardiovascular Diseases
HPO:Abnormality of the cardiovascular system Angina pectoris Congestive heart failure Coronary artery atherosclerosis Left ventricular dysfunction Myocardial infarction Right ventricular failure

Primary Outcomes

Description: Development of an electronic (e-HEALTH) framework structure for management of patients with known cardiovascular disease in COVID19 pandemic social context

Measure: Providing a special electronic platform (e-health) for remote managing cardiovascular outpatients

Time: 6 months

Description: patients come into direct contact with the case coordinator, who provides ongoing assistance, including for connecting to devices that ensure real-time data transmission and directing to specialist teams that establish stage diagnosis and management / therapy behavior (including adjustment). doses, decisions to discontinue medication or to add medication);

Measure: Number of patients included in this platform

Time: 6 months

Secondary Outcomes

Description: Will be the number of sessions per patient multiplied with the number of patients included

Measure: Number of consultations/sessions given

Time: 6 months

22 Efficacy of Hydroxychloroquine for Post-exposure Prophylaxis (PEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Adults Exposed to Coronavirus Disease (COVID-19): a Blinded, Randomized Study

This is a clinical study for the prevention of SARS-CoV-2 infection in adults exposed to the virus. This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) who are close contacts of persons with laboratory confirmed SARS-CoV-2 or clinically suspected COVID-19. Eligible participants will be enrolled and randomized to receive the intervention or placebo at the level of the household (all eligible participants in one household will receive the same intervention).

NCT04328961 COVID-19 Corona Virus Infection SARS (Severe Acute Respiratory Syndrome) SARS-CoV-2 Drug: Hydroxychloroquine Sulfate Drug: Ascorbic Acid
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected daily for 14 days

Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection

Time: Day 1 through Day 14 after enrolment

Description: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit

Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection

Time: Day 28 after enrolment

Secondary Outcomes

Description: Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults

Measure: Rate of participant-reported adverse events

Time: 28 days from start of Hydroxychloroquine therapy

Description: PCR-confirmed COVID-19 diagnosis

Measure: Incidence rates of COVID-19 through study completion

Time: 28 days from enrolment

23 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 COVID-19 Acute Respiratory Distress Syndrome Virus; Pneumonia Acute Lung Injury 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

24 Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS

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

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

Primary Outcomes

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

Time: From baseline to day 7

Secondary Outcomes

Measure: Lung injury score

Time: From baseline to day 28

Measure: Oxygenation index

Time: From baseline to day 28

Measure: In-hospital mortality

Time: From baseline to day 28

Measure: Mortality

Time: At day 28

Measure: Ventilator-free days

Time: From baseline to day 28

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

Time: From baseline to day 28

Measure: Cumulative use of sedatives

Time: From baseline to day 28

Measure: Cumulative duration of use of sedatives

Time: From baseline to day 28

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

Time: From baseline to day 28

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

Time: From baseline to day 28

Measure: ICU-acquired weakness and delirium

Time: From baseline to day 28

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

Time: From baseline to day 28

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

Time: At 6 months and 12 months

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

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

Measure: Anti-HLA antibodies plasmatic dosage

Time: From baseline to day 14, and at 6 months

25 Treatment of Severe Acute Respiratory Syndrome Caused by COVID-19 With Ruxolitinib

In December 2019, a new virus emerged in Wuhan, China rapidly becoming a pandemic with registered cases above 800,000 around the world. The virus is now known as SARS-CoV2 calling its disease coronavirus-19 or COVID-19. The mortality of the virus has been reported around 2-10% and its causes because of the proinflammatory immune response generated on the host. The cytokines involved in the immune response to COVID-19 are IL-1, IL-2, IL4, IL-6, IL-10, IL-12, IL-13, IL-17, GCSF, MCSF, IP-10, MCP-1, MIP-1α, HGF, IFN-γ y TNF-α. Ruxolitinib is an inhibitor of JAK 1/2 which is responsable for multiple cellular signals including the proinflammatory IL-6. Ruxolitinib works as and immunomodulator decreasing the cytotoxic T lymphocytes and increasing the Treg cells. This study is intended to stop the disregulated immune response caused by COVID-19 that generates the pneumonia and subsequent severe acute respiratory syndrome.

NCT04334044 COVID-19 Severe Acute Respiratory Syndrome Coronavirus 2 Drug: Ruxolitinib Oral Tablet
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Presence of recovery of pneumonia characterized by cease of respiratory symptoms

Measure: Recovery of Pneumonia

Time: 14 days

Secondary Outcomes

Description: Increment or decrease in mg/ml of C-reactive protein

Measure: Response of C-reactive protein

Time: 14 days

Description: Increment or decrease in ng/ml of ferritin

Measure: Response of Ferritin

Time: 14 days

Description: Increment or decrease in mg/ml of D-dimer

Measure: Response of D-dimer

Time: 14 days

Description: Requirement of Intensive Care Unit on the patients under treatment

Measure: Rate of ICU admission

Time: 14 days

Description: Requirement of mechanical ventilation on the patients under treatment

Measure: Rate of mechanical ventilation

Time: 14 days

Description: Time since the diagnosis to the last follow up (recovery or death)

Measure: Overall Survival

Time: 1 month

Description: Rate of adverse events associated with ruxolitinib

Measure: Toxicity Rate

Time: 1 month

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

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

NCT04335786 Respiratory Distress Syndrome, Adult SARS-CoV-2 Drug: Valsartan (Diovan) Drug: Placebo oral tablet
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Death is defined as all-cause mortality

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

Time: within 14 days

Secondary Outcomes

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

Measure: Death

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

Description: Occurrence of mechanical ventilation and time to ventilation

Measure: Mechanical ventilation

Time: within 14 days

Description: Occurrence of ICU admission and time to admission

Measure: Intensive care unit admission

Time: within 14 days

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

Measure: Occurrence of acute kidney injury

Time: Within 14 days

27 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 COVID-19 SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia Clinical Trial Drug: Chloroquine Diphosphate 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

28 Efficacy and Safety 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 and safety of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 420 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 MPS (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

NCT04343729 SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia Drug: Methylprednisolone Sodium Succinate 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: Number of patients with diagnosis of early onset of SARS

Measure: Proportion of patients with SARS

Time: after randomization, up to 7 days.

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.

29 Dexamethasone Combined With Hydroxychloroquine Compared to Hydroxychloroquine Alone for Treatment of Severe Acute Respiratory Distress Syndrome Induced by Coronavirus Disease 19 (COVID-19): a Multicentre, Randomised Controlled Trial

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

NCT04347980 Respiratory Distress Syndrome, Adult COVID-19 Drug: Dexamethasone and Hydroxychloroquine Drug: Hydroxychloroquine
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Mortality rate evaluated 28 days after randomization

Measure: Day-28 mortality

Time: 28 days after randomization

Secondary Outcomes

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

Measure: Ventilator-free days

Time: 28 days after randomization

Description: Mortality rate evaluated during Intensive care unit stay

Measure: Intensive Care Unit mortality

Time: Up to 60 days after randomization

Description: Mortality rate evaluated 60 days after randomization

Measure: Day-60 mortality

Time: 60 days after randomization

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

Measure: Nosocomial pneumonia

Time: Up to 60 days after randomization

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

Measure: Bacteremia

Time: Up to 60 days after randomization

Other Outcomes

Description: Placement of ECMO during intensive care unit stay

Measure: Extra corporeal membrane oxygenation (ECMO)

Time: Up to 60days after randomization

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

Measure: Tracheostomy

Time: Up to 60 days after randomization

Description: Number of Prone position session

Measure: Prone Position

Time: Up to 60 days after randomization

30 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

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

NCT04350580 Acute Respiratory Distress Syndrome COVID-19 Drug: Human immunoglobulin Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

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

Measure: Ventilator-free days

Time: 28 days

Secondary Outcomes

Measure: Mortality

Time: 28 and 90 days

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

Measure: Sequential Organ Failure Assessment Score

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

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

Measure: P/F ratio

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

Measure: Lung compliance

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

Description: Severity scoring of lung oedema on the chest radiograph

Measure: Radiological score

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

Description: Concentration in mg/L

Measure: Biological efficacy endpoints - C-reactive protein

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

Description: Concentration in microgram/L

Measure: Biological efficacy endpoints - Procalcitonin

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

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

Measure: Immunological profile

Time: Up to 28 days

Description: Use of corticosteroids, antiretroviral, chloroquine

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

Time: Up to 28 days

Measure: Occurrence of deep vein thrombosis or pulmonary embolism

Time: 28 days

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

Time: 28 days

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

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

Time: 28 days

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

Measure: Occurrence of adverse event related to immunoglobulins

Time: 28 days

Description: Medical research council sum score on awakening

Measure: Occurrence of critical illness neuromyopathy

Time: Up to 28 days

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

Measure: Occurrence of ventilator-acquired pneumonia

Time: Up to 28 days

31 Evaluation of Respiratory Mechanics and Lung Recruitment in Patients With SARS-CoV-2 Associated Acute Respiratory Distress Syndrome

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

NCT04350710 Acute Respiratory Distress Syndrome COVID Other: PEEP trial
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: no unit

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

Time: Day 1

Description: no unit

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

Time: Day 5

Description: no unit

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

Time: Day 10

Secondary Outcomes

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 1

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 5

Description: Arterial blood gases

Measure: PaO2/FiO2 (mmHg)

Time: Day 10

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 1

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 5

Description: mL

Measure: Lung volume recruited (VRec)

Time: Day 10

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 1

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 5

Description: Obtained by inspiratory pause of 5 seconds

Measure: Plateau pressure (cm H2O)

Time: Day 10

Measure: Oesophagal pressure (cm H2O)

Time: Day 1

Measure: Oesophagal pressure (cm H2O)

Time: Day 5

Measure: Oesophagal pressure (cm H2O)

Time: Day 10

Measure: weight (Kg)

Time: Day 1

Measure: weight (Kg)

Time: Day 5

Measure: weight (Kg)

Time: Day 10

Measure: urine output (mL)

Time: day 1

Measure: urine output (mL)

Time: day 5

Measure: urine output (mL)

Time: day 10

Measure: serum creatinine (Umo/L)

Time: day 1

Measure: serum creatinine (Umo/L)

Time: day 5

Measure: serum creatinine (Umo/L)

Time: day 10

Measure: Mean arterial pressure (mmHg)

Time: day 1

Measure: Mean arterial pressure (mmHg)

Time: day 5

Measure: Mean arterial pressure (mmHg)

Time: day 10

Measure: Peak Pressure (cm H2O)

Time: Day 1

Measure: Peak Pressure (cm H2O)

Time: Day 5

Measure: Peak Pressure (cm H2O)

Time: Day 10

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 1

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 5

Description: Obtained by expiratory pause of 5 seconds

Measure: PEEP total (cm H2O)

Time: Day 10

Measure: PEP Set (cm H2O)

Time: Day 1

Measure: PEP Set (cm H2O)

Time: Day 5

Measure: PEP Set (cm H2O)

Time: Day 10

Measure: Height (cm)

Time: Day 1

Measure: Airway pening pressure (cm H2O)

Time: day 1

Measure: Airway pening pressure (cm H2O)

Time: day 5

Measure: Airway pening pressure (cm H2O)

Time: day 10

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

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

Time: Day 1

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

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

Time: Day 5

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

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

Time: Day 10

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

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

Time: Day 1

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

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

Time: Day 5

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

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

Time: Day 10

32 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19.

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

NCT04351243 Lung Injury or Acute Respiratory Distress Syndrome Due to COVID-19 Drug: Gimsilumab Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome Wounds and Injuries

Primary Outcomes

Description: Mortality at Day 43

Measure: Primary endpoint

Time: 43 days

Secondary Outcomes

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

Measure: Number of ventilator-free days.

Time: Day 43

Measure: Number of days in the ICU

Time: Day 43

Measure: Number of days of inpatient hospitalization

Time: Day 43

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

Time: Days 15, 22, 29, and 43

33 Efficacy and Safety of Aerosolized Intra-tracheal Dornase Alpha Administration in Patients With COVID19-induced Acute Respiratory Distress Syndrome (ARDS)

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

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

Primary Outcomes

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

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

Time: Day 7

34 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 COVID-19 Pneumonia, Viral Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Biological: eculizumab
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia


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

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

NCT04355728 Corona Virus Infection ARDS ARDS, Human Acute Respiratory Distress Syndrome COVID-19 Biological: Umbilical Cord Mesenchymal Stem Cells Other: Standard of Care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

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

Measure: Incidence of pre-specified infusion associated adverse events

Time: Day 5

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

Measure: Incidence of Severe Adverse Events

Time: 90 days

Secondary Outcomes

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

Measure: Survival rate after 90 days post first infusion

Time: 90 days

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

Measure: Ventilator-Free Days

Time: 28 days or hospital discharge, whichever is earlier

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

Measure: Change in Oxygenation Index (OI)

Time: 28 days

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

Measure: Plat-PEEP

Time: 28 days

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

Measure: Sequential Organ Failure Assessment (SOFA) Scores

Time: 28 days

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

Measure: Small Identification Test (SIT) scores

Time: At baseline, day 18 and day 28.

Description: As assessed via serum blood samples.

Measure: Troponin I levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: C-Reactive Protein levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

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

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: D-dimer levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: 25-Hydroxy Vitamin D levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Alloantibodies levels

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Blood white cell count

Time: Baseline, 28 days

Description: As assessed via serum blood samples.

Measure: Platelets count

Time: Baseline, 28 days

36 Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection: A Phase 2a Clinical Trial

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

NCT04357730 Severe Acute Respiratory Syndrome Respiratory Failure Acute Respiratory Distress Syndrome Drug: Alteplase 50 MG [Activase] Drug: Alteplase 100 MG [Activase]
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

Primary Outcomes

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

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

Time: at 48 hours post randomization

Secondary Outcomes

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

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

Time: at 48 hours post randomization

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

Measure: National Early Warning Score 2 (NEWS2)

Time: at 48 hours post randomization

Description: The ordinal scale is an assessment of the clinical status as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. (combined items 7 and 8 as our study is limited to hospital).

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

Time: at 48 hours post randomization

Description: 48 hour mortality for hospitalized patients

Measure: 48 hour in-hospital mortality

Time: at 48 hours post randomization

Description: 14 days mortality for hospitalized patients

Measure: 14 days in-hospital mortality

Time: 14 days post randomization

Description: 28 days mortality for hospitalized patients

Measure: 28 days in-hospital mortality

Time: 28 days post randomization

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

Measure: ICU-free days

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

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

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

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

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

Measure: Ventilator-free days

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

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

Measure: Successful extubation

Time: Day 4 after initial extubation

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

Measure: Successful weaning from paralysis

Time: Day 4 after initial termination of paralytics

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

Measure: Survival to discharge

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

37 Impact of Dexmedetomidine Infusion on the Time Course and Outcomes of Acute Respiratory Distress Syndrome (ARDS) in Patients Affected by the SARS-CoV-2 (COVID-19) Admitted to Critical Care Unit

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

NCT04358627 Acute Respiratory Distress Syndrome Inflammation Dexmedetomidine Cytokine Storm Delirium, Emergence Drug: Dexmedetomidine Injectable Product
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Delirium Emergence Delirium Syndrome Inflammation

Primary Outcomes

Description: (Presence/Absence) requirement of mechanical ventilation

Measure: Mechanical ventilation

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

Secondary Outcomes

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

Measure: Duration of mechanical ventilation

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

Description: Delirium criteria as defined in DSM-4

Measure: Delirium on recovery from sedation

Time: First 24 hours after retiring dexmedetomidine sedation

38 The Effect of Prone Positioning on Lung Aeration and Ventilation-perfusion Matching in Mechanically Ventilated Patients With Coronavirus Disease Related Acute Respiratory Distress Syndrome

The consensus therapeutic strategy implies that COVID patients with acute lung injury due to coronavirus are routinely placed in prone position in an attempt to improve oxygenation by increasing ventilation homogeneity. The purpose of the study is quantify with the electrical impedance tomography (EIT) the changes in the ventilation and aeration in the dorsal regions of the lung when the patient is placed in prone position.

NCT04359407 Severe Acute Respiratory Syndrome Coronavirus 2 Electric Impedance Prone Positioning Other: Prone positioning
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

Primary Outcomes

Description: Change in the ratio of tidal electrical impedance variation in the dorsal and total lung areas

Measure: Tidal electrical Impedance

Time: One hour before turning to prone or supine positioning

Secondary Outcomes

Description: Changes in intrapulmonary shunt fraction

Measure: Intrapulmonary shunt

Time: One hour before turning to prone or supine positioning

Description: Changes in the phase three slope of the volumetric capnogram

Measure: Volumetric capnography

Time: One hour before turning to prone or supine positioning

39 COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study

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

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

Primary Outcomes

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

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

Time: 15 days

Secondary Outcomes

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

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

Time: 15 days

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

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

Time: 15 days

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

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

Time: 15 days

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

Measure: Improvement of respiratory performance - ratio values

Time: 15 days

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

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

Time: 15 days

Description: every 24 hours fibrinogen value in mg/dl

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

Time: 15 days

Description: every 24 hours transaminases value in U/L

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

Time: 15 days

Description: every 24 hours aPTT value in seconds

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

Time: 15 days

Description: every 24 hours INR value in %

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

Time: 15 days

Description: every 24 hours glycemia value in mg/dl

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

Time: 15 days

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

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

Time: 15 days

Description: Total leucocyte as CBC x10e)/L

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

Time: 15 days

Description: formula % on total leucocyte

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

Time: 15 days

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

Measure: Evaluation of the epidemiological parameters: Chest CT

Time: 15 days

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

Measure: Evaluation of the epidemiological parameters: Eco Chest

Time: 15 days

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

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

Time: 15 days

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

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

Time: 15 days

Description: Number of AE grade 1 to 4

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

Time: 15 days

40 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

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

NCT04365985 COVID-19 Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome (SARS) Coronavirus Infections Drug: Naltrexone Drug: Ketamine Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

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

Measure: Progression of oxygenation needs

Time: up to 1 month

Secondary Outcomes

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

Measure: Renal failure

Time: up to 1 month

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

Measure: Liver failure

Time: up to 1 month

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

Measure: Cytokine Storm

Time: up to 1 month

Description: Count of participants who die from COVID-19

Measure: Mortality

Time: up to 1 month post hospital discharge

Description: Length of hospital stay in days

Measure: Length of hospital stay

Time: up to 1 month

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

Measure: Intensive Care Unit (ICU) admission

Time: up to 1 month

Description: Length of ICU stay in days

Measure: Intensive Care Unit (ICU) duration

Time: up to 1 month

Description: Count of participants requiring intubation

Measure: Intubation

Time: up to 1 month

Description: Length of intubation, measured in days

Measure: Intubation duration

Time: up to 1 month

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

Measure: Time until recovery

Time: up to 1 month

41 Intermediate-size Expanded Access of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells for Acute Respiratory Distress Syndrome Due to COVID-19 Infection

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

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


42 Prevention and Treatment With Calcifediol of COVID-19 Coronavirus-induced Acute Respiratory Syndrome (SARS)

The administration of Calcifediol in patients with COVID-19, will reduce the development of SARS and the worsening of the various phases of the syndrome. Reducing at least 25% in ICU admission and death from the process, reducing days of hospitalization, facilitating the recovery of the same, acting significantly and positively, in any of its phases throughout the natural history of illness. As a treatment with extensive experience of clinical use, safe, inexpensive, and potentially very effective, it will have a highly efficient cost-benefit impact on the prevention of SARS.

NCT04366908 SARS-CoV 2 COVID19 SARS (Severe Acute Respiratory Syndrome) Cytokine Release Syndrome Cytokine Storm Drug: BAT + Calcifediol Drug: BAT
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

Primary Outcomes

Description: Proportion of subjects who enter the Intensive Care Unit

Measure: Admission to Intensive Care Unit

Time: At day 28.

Description: Proportion of subjects who die.

Measure: Death

Time: At day 28.

Secondary Outcomes

Description: Compare the time (in days) at discharge in newly hospitalized patients on non-invasive ventilation.

Measure: Time from onset of symptoms to discharge of patients in conventional hospitalization

Time: At day 28.

Description: In patients who, in the course of their evolution, required admission with mechanical ventilation in the ICU, time until admission to Intensive Care Unit

Measure: ICU - Time until admission

Time: At day 28.

Description: In patients who, in the course of their evolution, required admission with mechanical ventilation in the ICU, time until mechanical ventilation is removed.

Measure: ICU - Time mechanical ventilation is removed

Time: At day 28.

Description: Evaluation of the inflammatory markers related to IL disease. Blood samples will be collected and assessed in order to evaluate interleukins related with the interleukin storm using immunological tests.

Measure: Evaluation of the inflammatory markers related with the disease

Time: At day 28.

Description: Evaluation of the Vitamin D metabolites.

Measure: Vitamin D metabolites

Time: At day 28.

Description: Compare the evolution in SatO2

Measure: Evolution in SatO2

Time: At day 28.

Description: Compare the evolution in the Sat O2/FiO2 ratio

Measure: Evolution in the Sat O2/FiO2 ratio.

Time: At day 28.

Description: Compare the evolution in the degree of dyspnea using the analog Borg scale

Measure: Evolution in the degree of dyspnea

Time: At day 28.

Description: Compare the evolution of radiological findings by simple radiology in the recruited subjects since their beginning in the trial until they end the trial

Measure: Evolution of the improvement of radiological findings by simple radiology

Time: At day 28.

Description: Incidence of adverse events related to medication and its administration.

Measure: Incidence of adverse events

Time: At day 28.

Description: Incidence in the appearance of hemorrhagic or thrombotic phenomena.

Measure: Appearance of hemorrhagic or thrombotic phenomena

Time: At day 28.

43 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 COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome Pneumonia, Viral Biological: Ravulizumab 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: Change from baseline in SpO2/FiO2 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: Survival (based on all-cause mortality) at Day 60 and Day 90

Time: Baseline, Day 60, Day 90

Measure: Duration of hospitalization

Time: Baseline, Day 29

44 Interventional Study to Evaluate the Efficacy of Therapeutic Plasma Exchange (TPE) Alone or in Combination With Ruxolitinib in COVID-19 Positive Patients With PENN Grade 2, 3, 4 Cytokine Released Syndrome (CRS)

This protocol will evaluate the efficacy of Therapeutic Plasma Exchange alone or in combination with ruxolitinib in COVID positive patients with PENN grade 2, 3, 4 cytokine release syndrome. It is hypothesized that dual intervention of acute apheretic depletion of cytokines and concomitant suppression of production will produce superior amelioration of the cytokine load and to help to prevent cytokine load rebound. This protocol is envisioned as a pilot study (n=20) for hypothesis generation for future investigation.

NCT04374149 Cytokine Release Syndrome COVID19 Procedure: Therapeutic Plasma Exchange Drug: Ruxolitinib
MeSH:Syndrome

Primary Outcomes

Description: Defined as greater than or equal to 33% decrease in cytokine load in one-third or more participants

Measure: Overall Response Rate

Time: 14 days

45 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 COVID-19 Pneumonia 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

46 Comparison of the Efficacy and Safety of Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19. A Prospective Randomized Controlled Phase II Trial

This study compare the efficacy and safety of tocilizumab versus methylprednisolone in the cytokine release syndrome of patients with COVID-19

NCT04377503 Cytokine Release Syndrome Covid-19 Drug: Tocilizumab 180 MG/ML Drug: Methylprednisolone Sodium Succinate
MeSH:Syndrome

Primary Outcomes

Description: A seven-category ordinal scale consisting of: 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: Patient clinical status 15 days after randomization

Time: 15 days after randomization

Secondary Outcomes

Description: Improvement in PaO2/FIO2

Measure: Improving oxygenation

Time: 15 days

Description: Improvement in the computed tomography between D0 and D10 after randomization

Measure: Thorax CT improvement

Time: 10 days

Description: Duration o ICU stay in days

Measure: ICU length of stay

Time: 28 days

Description: Days of mechanical ventilation

Measure: Duration of mechanical ventilation

Time: 28 days

Description: AKI according to Kidney Disease Improving Global Outcomes (KDIGO)

Measure: Incidence of acute kidney (AKI) with necessity of renal replacement therapy

Time: 15 days

47 A Prospective, Randomized, Controlled Study Assessing Vagus Nerve Stimulation in CoViD-19 Respiratory Symptoms (SAVIORII)

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

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

Primary Outcomes

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

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

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

Secondary Outcomes

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

Measure: evaluate cytokine trends

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

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

Measure: evaluate supplemental oxygen requirements

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

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

Measure: decrease mortality of CoViD-19 patients

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

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

Measure: delay onset of ventilation

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

48 Inhaled Sedation in COVID-19-related Acute Respiratory Distress Syndrome (ISCA): an International Research Data Study in the Recent Context of Widespread Disease Resulting From the 2019 (SARS-CoV2) Coronavirus Pandemics (COVID-19)

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

NCT04383730 Critically Illness Sedation Invasive Mechanical Ventilation Acute Respiratory Distress Syndrome Drug: Intravenous sedation Drug: Inhaled sedation
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

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

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

Time: Day 28 after inclusion

Secondary Outcomes

Description: All-cause mortality

Measure: All-cause mortality

Time: Days 7, 14, and 28 after inclusion

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

Measure: Ventilator-free days

Time: Days 7 and 14 after inclusion

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

Measure: ICU-free days

Time: Day 28 after inclusion

Description: Total duration of controlled mechanical ventilation to day 28

Measure: Duration of invasive mechanical ventilation

Time: Day 28 after inclusion

Description: Total duration of controlled mechanical ventilation to day 28

Measure: Duration of controlled mechanical ventilation

Time: Day 28 after inclusion

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

Measure: Physiological measures of lung function

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

Description: Partial pressure of arterial carbon dioxide (PaCO2)

Measure: Physiological measures of lung function

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

Description: Inspiratory plateau pressure

Measure: Physiological measures of lung function

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

Description: Driving pressure

Measure: Physiological measures of lung function

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

Description: Mode of mechanical ventilation (assisted versus controlled)

Measure: Physiological measures of lung function

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

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

Measure: Physiological measures of lung function

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

Description: Development of pneumothorax

Measure: Development of complications

Time: Day 7 from inclusion

Description: Supraventricular tachycardia

Measure: Development of complications

Time: Day 7 from inclusion

Description: New onset atrial fibrillation

Measure: Development of complications

Time: Day 7 from inclusion

Description: Total duration (in days) of vasopressor use

Measure: Duration of vasopressor use

Time: Day 28 after inclusion

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

Measure: Duration of renal replacement therapy

Time: Day 28 after inclusion

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

Measure: Duration (in days) of any adjuvant therapies

Time: Day 7 from inclusion

Description: Number of days with continuous neuromuscular blockade

Measure: Duration of continuous neuromuscular blockade

Time: Day 28 from inclusion

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

Measure: Type of sedation practices

Time: Day 28 from inclusion

Description: Number of days with sedation

Measure: Duration of sedation practices

Time: Day 28 from inclusion

Description: If inhaled sedation, device used to deliver it

Measure: Modalities of sedation practices

Time: Day 28 from inclusion

49 Characterization of the Clinical, Biological and Histological Pulmonary and Renal Damage Associated With the SARS-CoV-2 Syndrome in Patients Admitted in the Intensive Care Unit

Renal damage in patients hospitalized for ARDS in the ICU can also be related to multiple causes including, but not limited to, the consequences of hemodynamic fluctuations in these patients or the use of nephrotoxic drugs responsible for acute post-ischemic or toxic tubular necrosis. Frequently observed abnormalities of cioagumation may also have a potential impact on renal structures, particularly glomerular capillaries. The researchers wish to characterize and phenotype the renal impairment of patients hospitalized in intensive care with tables of severe Covid19 infections in ARDS: clinical, biological and histological (by performing post-mortem biopsies). Translated with www.DeepL.com/Translator (free version)

NCT04385004 Acute Respiratory Distress Syndrome
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: Characterisation of Clinical, Biological and Histological Pulmonary and Renal Impairment Related to SARS-CoV-2

Time: 1 month

50 COVID-19 Hyperinflammation Syndrome (COV-HI): Protocol for a Rapidly Executed Cohort Study

Based on emerging experience and trials from countries affected early by the COVID-19 (COV19) pandemic, there is evidence that a subgroup of severely affected people develop a hyperinflammatory (HI) syndrome (COV-HI). Trials are in progress of cytokine inhibition and other immune modulation to treat COV-HI. This proposal aims to use a rapidly executed cohort study to characterise the clinical phenotypes of COV-HI in patients in the UK through an established and nimble network of clinicians and scientists with broad experience of identifying and treating HI. The aim is to confirm the COV-HI clinical phenotype and using routine data to try to infer the inflexion point where COV-HI emerges. This would enable refinement of the proposed treatment algorithm and translates to routine clinical practice to improve the outlook for COV-HI.

NCT04385069 COV-HI COVID-19 COVID-19 (COV) Hyperinflammatory (HI) Syndrome
MeSH:Syndrome

Primary Outcomes

Description: Confirm positive diagnosis within electronic hospital records and collate selected demographic data from eligible patients identified.

Measure: To collect retrospective demographic information on 500 people admitted to selected hospital sites across the UK with a COVID-19 diagnosis confirmed through positive laboratory PCR swab.

Time: within 3 months

Description: Research staff will review the electronic patient record for all eligible participants and record the results of each patients routine blood tests, chest x-rays, echos and any other associated clinical investigations conducted during the course of their admission onto a database for analysis.

Measure: To record the results of each patient's measured medical observations, clinical investigations and outcomes during the course of their admission.

Time: within 3 months

Description: Research staff will record data collected from eligible patients' electronic medical records from routine blood tests, chest x-rays, echos and any other associated clinical investigations conducted during the course of their admission onto a database and conduct comprehensive analysis.

Measure: To conduct retrospective analysis of data collected to map each patient's clinical journey during their admission

Time: within 3 months of data collection

51 Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS)

To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).

NCT04388826 Respiratory Distress Syndrome, Adult Drug: Veru-111
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision making is driven solely by resource limitation

Measure: Proportion of subjects that are alive without respiratory failure at Day 29.

Time: Day 29

Secondary Outcomes

Description: Improvement on the WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale)

Measure: WHO clinical Improvement

Time: Day15 Day 22 and Day 29

Description: Proportion of subjects with normalization of fever and oxygen saturation through

Measure: Normalization of Fever and Oxygen

Time: Day 15, Day 22, and Day 29

Description: Percentage of subjects discharged from hospital

Measure: Discharge from Hospital

Time: Day 15 and Day 22

Description: Proportion of patients alive and free of respiratory failure

Measure: Patients alive and free of respiratory failure

Time: Day 15, and Day 22

52 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

NCT04390139 COVID-19 SARS-CoV 2 Adult Respiratory Distress Syndrome Drug: XCEL-UMC-BETA Other: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respi Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of patients who died, by treatment group

Measure: All-cause mortality at day 28

Time: Day 28

Secondary Outcomes

Description: Number of patients with treatment-emergent adverse events, by treatment group

Measure: Safety of WJ-MSC

Time: Day 28

Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group

Measure: Need for treatment with rescue medication

Time: Day 28

Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

Measure: Need and duration of mechanical ventilation

Time: Day 28

Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

Measure: Ventilator free days

Time: Day 28

Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

Measure: Evolution of PaO2 / FiO2 ratio

Time: Day 28

Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

Measure: Evolution of the SOFA index

Time: Day 28

Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

Measure: Evolution of the APACHE II score

Time: Day 28

Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

Measure: Duration of hospitalization

Time: Day 28

Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

Measure: Evolution of markers of immune response (leucocyte count, neutrophils)

Time: Day 28

Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: D-dimer

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: Ferritin

Time: Day 28

Other Outcomes

Description: Blood sample analysis

Measure: Analysis of subpopulations of lymphocytes and immunoglobulins

Time: Day 28

Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)

Measure: Evaluation of the in vitro response of the receptor lymphocytes

Time: Day 28

Description: Reactivity will be assessed using ELISPOT

Measure: Study of reactivity against SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis

Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis for the patient's genomic sequencing

Measure: Genetic variability of patient's genotype in response to treatment

Time: Day 28

Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment

Time: Day 28

53 Safety and Efficacy of Intravenous Infusion of Wharton's Jelly Derived Mesenchymal Stem Cell Plus Standard Therapy for the Treatment of Patients With Acute Respiratory Distress Syndrome Diagnosis Due to COVID 19: A Randomized Controlled Trial

Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis. Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation. These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.

NCT04390152 Acute Respiratory Distress Syndrome Drug: Wharton's jelly derived Mesenchymal stem cells. Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.

Measure: Intergroup mortality difference with treatment

Time: 28 days.

Secondary Outcomes

Description: Safety evaluation of WJ-MSC describing and comparing incidence, type and severity of adverse events in both groups.

Measure: Number of patients with treatment related adverse events

Time: 6 months.

Description: Evaluation of the effect of WJ-MSC in the time of mechanical ventilation compared between the two groups, as prolonged mechanical ventilation days are associated with higher complication risks as pneumonia, tracheostomy and death.

Measure: Difference in days of mechanical ventilation between groups

Time: From ICU admission to 180 days.

Description: Evaluation of the effect of WJ-MSC in the time of hospitalization between the two groups as a measure of efficacy.

Measure: Median reduction of days of hospitalization

Time: From hospital admission to 180 days.

Description: Evaluation of the effect of WJ-MSC in the time of oxygen needs compared between the two groups as a measure of efficacy.

Measure: Median reduction of days of oxygen needs

Time: From hospital admission to 180 days.

Description: "Sequential Organ Failure Assessment" (SOFA) score is a tool used to determine the beginning and evolution of multiorgan failure, ranging from 0 to 24, being 24 the worst scenario. It has been proven useful as an outcome predictor of mortality and ICU stay. The result is the addition of the evaluation of each organ or system. Effect of WJ-MSC in the SOFA score will be compared between the two groups.

Measure: Difference between "Sequential Organ Failure Assessment" score between groups

Time: Baseline to 7 days

Description: Murray score is a tool used to classify lung injury. 0 = no lung injury, 0.1-2.5, mild to moderate lund injury, >2.5 Acute respiratory distress syndrome. The effect of WJ-MSC in the Murray score will be compared between the two groups.

Measure: Difference between median Murray score between groups

Time: Baseline and 7 days

Description: APACHE II is a prognostic score based on 12 different items obtained in the first 24 hours of ICU admission. Its mainly used as a single measure, but some authors have used and described prediction usefulness with repeated measures. It ranges from 0 to 71 points. Higher scores are related to higher ICU mortality. The effect of WJ-MSC in the APACHE II score will compared between the two groups.

Measure: Difference in APACHE II score between groups

Time: Baseline and 7 days

Description: Evaluation of the effect of WJ-MSC in lymphocyte count measured in absolute number/mm3. These laboratory measures have been associated with COVID 19 severity.

Measure: Difference in lymphocyte count between groups

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in C reactive protein concentration between the two groups, measured in mg/dl. Highest levels have been associated with COVID 19 severity and inflammation.

Measure: Changes in C reactive protein concentration between groups

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in D dimer between the two groups, measured in micrograms Highest levels have been associated with COVID 19 severity and thromboembolic complications.

Measure: Changes in D dimer concentration

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in ferritin compared between the two groups, measured in nanograms/ml. These laboratory measures have been associated with COVID 19 infection and severity.

Measure: Changes in ferritin concentration

Time: baseline and 21 days or discharge

Description: Evaluation of the effect of WJ-MSC in LDH compared between the two groups, measured in units/liter. These laboratory measures have been associated with COVID 19 infection and severity.

Measure: Changes in lactate dehydrogenase concentration

Time: baseline and 21 days or discharge

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation.The effect of WJ-MSC in IL-6 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 6 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 8 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 8 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 10 will be compared between the two groups. It will be measured in picograms/ml.

Measure: Impact on interleukin 10 concentrations between groups.

Time: Baseline and 7 days

Description: Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in TNF alpha will be compared between the two groups. It will be measured in nanograms/ml.

Measure: Impact on tumor necrosis factor alpha concentrations between groups.

Time: Baseline to 7 days.

Other Outcomes

Description: Evaluation of the effect of WJ-MSC in pulmonary function measured with 6 minute walk. 6 minute walk is a test that gives information about pulmonary, cardiovascular and musculoskeletal functions. It measures the distance walked in 6 minutes in meters.

Measure: Changes in 6 minute walk between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in pulmonary function with thoracic CT scan. CT scan gives information about lung parenchyma, showing acute and chronic changes related to the underlying condition. Radiologic findings will be compared mainly comparing percentage of patients with pulmonary fibrosis.

Measure: Changes in Pulmonary Computed Tomography Scan between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in pulmonary function measured with spirometry, compared between the two groups. Spirometry gives information about lung volume and mobilization of air. Main parameters to be measured in spirometry are Forced Vital Capacity, Forced Expiratory Volume in 1 second and relation between these two to define if there is obstruction or restriction of airflow.

Measure: Changes in Spirometry between groups

Time: 6 months

Description: Evaluation of the effect of WJ-MSC in health related quality of life assessed by 36 Item Short Survey (SF-36). SF 36 is a patient reported tool. Each question is rated from 0 to 100, being 100 the best score possible. The scores are then compared to a population defined median score. Differences in global and specific scoring will be measured between groups.

Measure: Changes in health related quality of life between groups

Time: 6 months

54 Early Care, Therapeutic Education, and Psychological Intervention for the Management of Post-intensive Care Syndrome and Chronic Pain After Coronavirus Disease 2019 Infection. Simple-blind, Controlled, Randomized Trial.

COVID-19 (coronavirus 2019) disease has led to a large number of hospital admissions, many of which require admission to intensive care (ICU). Post-intensive care syndrome (PICS) is defined as deterioration or worsening of previous deterioration in the mental, physical or cognitive status that appears as a consequence of a critical illness and which persists after acute hospital care. Also, there is evidence that patients who survive a critical illness have a high prevalence of moderate to extreme chronic pain. Patients with COVID-19 disease are an especially susceptible population to develop PICS due to acute respiratory distress syndrome (ARDS) survivors have significant long-term deterioration in mental, cognitive, and functional health. This study hypothesis is that a specific care program based on early therapeutic education and psychological intervention improves the quality of life of patients at risk of developing PICS and chronic pain after COVID-19 disease.

NCT04394169 Post ICU Syndrome Chronic Pain Covid-19 Behavioral: Intervention program
MeSH:Syndrome Chronic Pain
HPO:Chronic pain

Primary Outcomes

Description: Health-related quality of life reported by the patient assessed through the visual analogue scale of the EQoL 5D/5L questionnaire at six months after discharge. [European quality of life 5 dimensions/5 levels ; from 0 (the worst imaginable health) to 100 (the best imaginable health) ]

Measure: Impact of intervention program on health-related quality of life (VAS)

Time: Six months after discharge

Secondary Outcomes

Description: Health-related quality of life reported by the patient assessed through the visual analogue scale of the EQoL 5D / 5L questionnaire at three months after discharge. [European quality of life 5 dimensions/5 levels ; from 0 (the worst imaginable health) to 100 (the best imaginable health)]

Measure: Impact of intervention program on health-related quality of life (VAS)

Time: Three months after discharge.

Description: Health-related quality of life reported by the patient assessed through health index of the EQoL 5D/5L questionnaire at three months after discharge. [European quality of life 5 dimensions/5 levels ; the questionnaire assesses quality of life in study participants according to 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each scored according to a scale of 1 (no problems) to 5 (indicating extreme problems) and generating a 5-digit code corresponding to quality of life]

Measure: Impact of intervention program on health-related quality of life (Index)

Time: Three months after discharge

Description: Health-related quality of life reported by the patient assessed through health index of the EQoL 5D/5L questionnaire at six months after discharge. [European quality of life 5 dimensions/5 levels ; the questionnaire assesses quality of life in study participants according to 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each scored according to a scale of 1 (no problems) to 5 (indicating extreme problems) and generating a 5-digit code corresponding to quality of life]

Measure: Impact of intervention program on health-related quality of life (Index)

Time: Six months after discharge

Description: Chronic pain intensity defined by BPI questionnaire (short version), at three and six months after discharge. [Brief pain inventory; A multidimensional questionnaire that evaluates pain intensity in the last 24 hours (worst, lowest, average) and current (right now). The questions are rated on a scale of 0 to 10, with 10 being the worst possible value. Subsequently, the average intensity score (BPI intensity score) is calculated.]

Measure: Impact of intervention program on chronic pain (intensity)

Time: Three and six months after discharge.

Description: Limitation of daily activities due to chronic pain, defined by BPI (short version), at three and six months after discharge. [Brief pain inventory; Multidimensional questionnaire that assesses the impact of pain on daily activities (general activity, encouragement, work, relationships with other people, sleep, enjoying life and the ability to walk). The questions are rated on a scale of 0 to 10, with 10 being the worst possible value. Subsequently, the mean score of the responses related to pain interference in activities (BPI interference score) is calculated.]

Measure: Impact of intervention program on chronic pain (limitation of daily activities)

Time: Three and six months after discharge.

Description: Pain catastrophization assessed by Pain Catastrophizing Scale at three and six months after hospital discharge. [Pain Catastrophizing Scale; Consisting of 13 questions that explore the frequency of thoughts and feelings that the interviewees have in the presence of current or anticipated pain, which are grouped into three scoring subscales (magnification, rumination and defenselessness). Each question is rated on a 5-point scale (0: not at all; 4: all the time). Being the maximum total score of 52 points.]

Measure: Impact of intervention program on chronic pain (Pain catastrophization)

Time: Three and six months after discharge.

Description: Clinically significant anxiety or depression symptoms prevalence at three and six months, assessed by the HAD test. [hospital anxiety and depression test; 14 questions, with two subscales, one for anxiety and the other for depression, with seven items each, the maximum score is 21 for each subscale. The cut-off points from zero to seven imply the absence of clinically relevant anxiety and depression, from eight to ten symptoms that require consideration and from 11 to 21 reports the presence of relevant symptoms, with a very probable diagnosis of anxiety or depression.]

Measure: Impact of intervention program on anxiety or depression incidence

Time: Three and six months after discharge.

Description: Probable post-traumatic stress syndrome prevalence at three and six months after discharge assessed by the DSM ( Diagnostic and Statistical Manual of Mental Disorders) V PTSD Checklist questionnaire (PCL-5) [PTSD Checklist questionnaire; It contains 20 questions that correspond to the DSM V PTSD (Post Traumatic Stress Disorder) criteria. Participants rated their symptoms on a scale of 0 (not at all), 1 (slightly), 2 (moderately), 3 (quite) to 4 (extremely), with a score ranging from 0 to 80. A total of the severity of the symptoms can be made, adding the score of each question (interval 0-80). The severity of each symptom can be evaluated, adding the score of the questions. The cut-off point to use for a provisional diagnosis of PTSD is 31 points.]

Measure: Impact of intervention on probable post-traumatic stress syndrome incidence

Time: Three and six months after discharge.

55 Randomized-controlled Trial of HFNC Alone vs HFNC and Awake Self-proning for Treatment of Severe COVID-19

Prone positioning is an established intervention in mechanically ventilated acute respiratory distress syndrome (ARDS) patients, with demonstrated reductions in mortality. Preliminary data suggest that awake proning in patients with COVID-19 treated with high-flow nasal oxygenation (HFNO) improves gas exchanges, and might be associated with a reduced need of mechanical ventilation, and reduced mortality. Further investigation in a formal randomized-controlled trial is need.

NCT04395144 Coronavirus Coronavirus Infection COVID Severe Acute Respiratory Syndrome Respiratory Failure Respiratory Insufficiency Respiratory Distress Syndrome ARDS Lung Diseases Procedure: Awake Prone Positioning Procedure: Standard care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Pulmonary Valve Insufficiency Syndrome
HPO:Abnormal lung morphology Pulmonary insufficiency

Primary Outcomes

Measure: Rate of Therapeutic failure, defined as a combined outcome of rate of intubation or death

Time: Up to 28 days after randomization

Secondary Outcomes

Measure: Intubation rate

Time: Up to 28 days after randomization

Measure: Mortality

Time: Up to 28 days after randomization

Measure: Days spent on mechanical ventilation

Time: Until discharge, up to 24 weeks after randomization

Measure: Days spent in the ICU

Time: Until discharge, up to 24 weeks after randomization

Measure: Hospital stay (in days)

Time: From admission to discharge, up to 24 weeks after randomization

Other Outcomes

Description: Total time spent in prone position, as recorded by nursing or respiratory therapists

Measure: Time in prone position

Time: Up to 28 days post randomization

Description: Daily evolution of oxygenation

Measure: Oxygenation (SpO2/FiO2 ratio)

Time: Until HFNC weaning, or up to 14 days after randomization, whichever is first

56 A Phase 2 Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor, AMY-101, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 (SAVE)

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection. We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.

NCT04395456 Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19) Drug: AMY-101 Other: WFI 5% glucose
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Measure: The proportion of patients who are alive, without evidence of ARDS (i.e. PaO2/FIO2 >300 mm Hg), who do not require any oxygen support (in room air).

Time: 21 days

Description: The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.

Measure: The proportion of patients assigned to each category, of a six-category ordinal scale.

Time: 21 days

Secondary Outcomes

Description: The clinical status is based on the following six-category ordinal scale: 1: not hospitalised; 2: hospitalised, not requiring supplemental oxygen; 3: hospitalised, requiring supplemental oxygen; 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and 6: death.

Measure: The proportion of patients assigned to each category, of a six-category ordinal scale.

Time: On days 7, 14, and 44

Measure: Proportion of patients surviving

Time: Through to day 44

Description: With respiratory failure defined as any of the following: Worsening of severe gas transfer deficit, accounting for a shift in ARDS disease category (PaO2/FiO2 ≤200 for patients with PaO2/FiO2 >200 at baseline; PaO2/FiO2 ≤100 for patients with PaO2/FiO2 >100 at baseline), Persistent respiratory distress while receiving oxygen (persistent marked dyspnea,use of accessory respiratory muscles, paradoxical respiratory movements), Transfer to the intensive care unit for intubation, Death.

Measure: Proportion of respiratory failure-free survival

Time: Day 44

Measure: Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)

Time: Through day 44

Measure: Cumulative incidence of freedom from oxygen requirement

Time: Through day 44

Measure: Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS

Time: Within 14 days after inclusion in the study

Measure: Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS

Time: Within 14 days after inclusion in the study

Measure: Proportion of patients developing thrombotic microangiopathies

Time: Through day 44

Measure: Changes in PaO2 and PaO2/FIO2

Time: Through day 44

Measure: Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)

Time: Through day 44

Measure: Changes in maximal and minimal cardiovascular parameters: Respiratory rate

Time: Through day 44

Measure: Changes in maximal and minimal cardiovascular parameters: Heart Rate

Time: Through day 44

Measure: Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Length of stay in ICU

Time: Through day 44

Measure: Cumulative incidence of discharge from hospital

Time: Through day 44

Measure: Number of adverse events

Time: Through day 44

Measure: Changes in levels of anti-drug antibodies

Time: On day 0 , 14 and 44

Measure: Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of Club Cell protein CC16 (biomarker of lung damage )

Time: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Measure: Changes in levels of AMY-101 plasma level

Time: On days 1, 2, 4, 7, 10, 14, 15, 21

57 Cellular Immuno-Therapy for COVID-19 ARDS (CIRCA-19) the Vanguard Study

The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). ARDS often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world's first clinical trial using MSC therapy for patients with severe infections (sepsis) which is often associated with ARDS (NCT02421484). This trial demonstrated tolerability, and potential signs of efficacy. In addition, the investigators have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in three different clinical studies. The investigators propose a Phase 1, open label, dose-escalating and safety trial using a 3+3+3 design to determine the safety, and maximum feasible tolerated dose of repeated delivery of Bone Marrow (BM)-MSCs intravenously. This will take advantage of a limited supply of screened BM-MSCs lines which are available now in the GMP facility and will allow to have product ready to deliver to the first patient within weeks. The investigators will enroll up to 9 patients; each receiving repeated unit doses of BM-MSCs delivered by IV infusion on each of 3 consecutive days (24±4 hours apart) according to the following dose-escalation schedule (3 patients per dose panel): (i) Panel 1: 25 million cells/unit dose (cumulative dose: 75 million MSCs), (ii) Panel 2: 50 million cells/unit dose (cumulative dose: 150 million MSCs), (iii) Panel 3: up to 90 million cells/unit dose (cumulative dose: up to 270 million MSCs).

NCT04400032 Acute Respiratory Distress Syndrome Covid19 Biological: Mesenchymal Stromal Cells
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 to determine the maximum feasible tolerated dose (MFTD) of BM-MSCs given to patients with COVID-19

Measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

Time: At time of infusion until one year post-infusion

Secondary Outcomes

Description: Number of Participants alive by Day 28

Measure: Number of Participants alive by Day 28

Time: Day 28

Description: Number of Participants with ventilator-free Days by Day 28

Measure: Number of Participants with ventilator-free Days by Day 28

Time: Day 28


HPO Nodes