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 |
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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 |
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drug126 | BLD-2660 Wiki | 0.13 |
drug712 | MultiStem Wiki | 0.13 |
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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 |
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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 |
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drug928 | Questionnaires for specific phobia Wiki | 0.13 |
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drug111 | Azithromycin 500 mg Wiki | 0.13 |
drug505 | Hydroxychloroquine Wiki | 0.13 |
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drug977 | Ruxolitinib Wiki | 0.10 |
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drug379 | Doxycycline Wiki | 0.09 |
drug839 | Peripheral blood draw Wiki | 0.09 |
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drug1135 | Telmisartan Wiki | 0.09 |
drug1397 | standard care Wiki | 0.09 |
drug905 | Prone positioning Wiki | 0.09 |
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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 |
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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 |
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 |
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
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
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.
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.
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.
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.
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 7Description: Incidence of SAEs
Measure: Incidence of Serious Adverse Events (SAEs) Time: 28 daysDescription: SOFA score is a measure of organ failure
Measure: Sequential Organ Failure Assessment (SOFA) score Time: Days 4, 7 and 14Description: Crs is a physiological measure of pulmonary function in ARDS
Measure: Respiratory compliance (Crs) Time: Days 4, 7 and 14Description: 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 14This 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
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.
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 vaccinationDescription: 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 monthsBackground: 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 recruitmentDescription: 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 recruitmentDescription: number of patients who required tracheostomy
Measure: Tracheostomy rate Time: During ICU stay up to one month after the start of recruitmentThe 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 90Description: 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 valuesThe 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 90Description: 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 28A 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
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 vaccinationDescription: 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 regimenThe 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).
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 treatmentDescription: Composite outcome in which: Death=0, Days of treatment =1
Measure: SARS-free days at 28 days Time: 28 daysDescription: Composite outcome in which: Death=0, Days of treatment =1
Measure: SARS -free days at 90 days Time: 90 daysDescription: Incidence
Measure: Renal Replacement Therapy Time: 28 daysDescription: Incidence
Measure: Liver Failure Time: 28 daysDescription: Incidence of patients requiring VA-ECMO, LVAD, IABP
Measure: Mechanical Support of Circulation Time: 28 daysDescription: In ambient air if possible
Measure: PaO2/FiO2 ratio in ambient air Time: daily for 28 daysCurrently, 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.
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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksSevere 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
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 hoursDescription: 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 daysDescription: 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 daysDescription: Proportion of patients surviving at 28 days within each group and comparison between groups.
Measure: Survival at 28 days from enrollment Time: 28 daysDescription: Proportion of patients surviving at 90 days within each group and comparison between groups.
Measure: Survival at 90 days from enrollment Time: 90 daysDescription: Expressed as PaO2/FiO2 ratio within each group and comparison between groups.
Measure: Daily oxygenation in the two groups until day 28 Time: 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Average days without need for mechanical ventilation within each group and comparison between groups.
Measure: Ventilator-free day at 28 days Time: 28 daysDescription: 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 daysDescription: Average days out of ICU within each group and comparison between groups.
Measure: ICU-free days at 28 days Time: 28 daysDescription: Average days of ICU admission within each group and comparison between groups.
Measure: ICU length of stay Time: 90 daysEvaluation of the efficacy and safety of TCM differential treatment of COVID-19 in Jiangsu Province based on a prospective multicenter cohort study.
Description: disappearance of fever, cough and shortness of breath/ the rate of complete relief /.
Measure: The relief / disappearance rate of main symptoms Time: 9dayDescription: 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: 9dayDescription: detection negative rat of nasopharyngeal swab, conjunctival sac secretion virus nucleic acid e
Measure: Virus antigen negative conversion rate Time: 9dayDescription: 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: 9dayDescription: the number of severe and critical cases occurred after the start of intervention.
Measure: The number of severe and critical conversion cases Time: 9dayDescription: 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: 9dayDescription: 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: 9dayDescription: Changes in c-reactive protein.
Measure: CRP changes Time: 9dayDescription: Changes in erythrocyte sedimentation rate.
Measure: ESR changes Time: 9dayDescription: Changes in procalcitonin.
Measure: PCTchanges Time: 9dayDescription: Changes of CD4+ and CD8+
Measure: The index of T cell subsets changed Time: 9daySome 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.
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 daysDescription: Measured in days
Measure: Duration of hospitalization Time: Up to 28 daysDescription: 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 daysDescription: Blood routine test
Measure: Change from baseline in white blood cell and differential count Time: Day 1 through Day 28Description: Oropharyngeal or anal swabs
Measure: Time to first negative in 2019 novel Corona virus RT-PCR test Time: Up to 28 daysDescription: Date and cause of death (if applicable).
Measure: All-cause mortality Time: up to 12 weeksDescription: Serum hsCRP
Measure: Change from baseline in hsCRP Time: Day 1 through Day 28Description: 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 28Description: 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)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.
Description: Mortality
Measure: Mortality Time: 5 Days with followup through 30 daysDescription: Index of Respiratory Distress
Measure: PaO2:FiO2 ratio Time: 5 Days with followup through the end of telemetry monitoringDescription: TNF alpha levels as measured in hospital laboratory
Measure: TNF alpha Time: 5 DaysDescription: Multi-system organ failure free days
Measure: Multi-system organ failure free days Time: 5 days with followup through 30 daysThe study aims to investigate organ dysfunction and biomarkers in patients with suspected or verified COVID-19 during intensive care at Uppsala University Hospital.
Description: KDIGO AKI score
Measure: Acute Kidney Injury Time: During Intensive Care, an estimated average of 10 days.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 daysDescription: Death within 1 year of ICU admission
Measure: 1 year mortality Time: 1 yearDescription: Development of Chronic Kidney Disease
Measure: Chronic Kidney Disease Time: 60 days and 1 year after ICU admissionDescription: Sequential Organ Failure Score as a continuous variable
Measure: SOFA-score Time: During Intensive Care, an estimated average of 10 days.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.
Description: proportion of deaths at day 28 between groups compared
Measure: Mortality rate reduction of 50% by day 28 Time: 28 days after randomizationDescription: 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 doseDescription: 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 doseDescription: clinical status
Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization Time: during and after intervention, up to 28 daysDescription: supplemental oxygen
Measure: Duration of supplemental oxygen (if applicable) Time: during and after intervention, up to 28 daysDescription: mechanical ventilation
Measure: Duration of mechanical ventilation (if applicable) Time: during and after intervention, up to 28 daysDescription: hospitalization
Measure: Absolute duration of hospital stay in days Time: during and after intervention, up to 28 daysDescription: adverse events grade 3 and 4
Measure: Prevalence of grade 3 and 4 adverse events Time: during and after intervention, up to 28 daysDescription: adverse events
Measure: Prevalence of serious adverse events Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum creatinine compared to baseline
Measure: Change in serum creatinine level Time: during and after intervention, up to 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: virus clearance from respiratory tract secretion
Measure: Change in detectable viral load in respiratory tract swabs Time: during and after intervention, up to 28 daysDescription: viremia in blood detected through RT-PCR
Measure: Viral concentration in blood samples Time: during and after intervention, up to 28 daysDescription: death
Measure: Absolute number of causes leading to participant death (if applicable) Time: during and after intervention, up to 28 daysCOVID-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.
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 daysDescription: Yes/no
Measure: death Time: 28 daysDescription: yes/no
Measure: Admission to ICU Time: 28 daysDescription: yes/no
Measure: Endotracheal intubation (invasive mechanical ventilation) Time: 28 daysDescription: mg/L
Measure: reduction of C-reactive protein or CRP Time: 14 days and 28 daysDescription: number of days free from mechanical ventilation (invasive or not)
Measure: Reduction of mechanical ventilation Time: 28 daysManagement 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.
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 monthsDescription: 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 monthsDescription: Will be the number of sessions per patient multiplied with the number of patients included
Measure: Number of consultations/sessions given Time: 6 monthsThis 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).
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 enrolmentDescription: 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 enrolmentDescription: 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 therapyDescription: PCR-confirmed COVID-19 diagnosis
Measure: Incidence rates of COVID-19 through study completion Time: 28 days from enrolmentA 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.
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 treatmentDescription: Evaluation by chest CT
Measure: Changes of lung imaging examinations Time: Within 28 days after treatmentDescription: Marker for SARS-CoV-2
Measure: Time to SARS-CoV-2 RT-PCR negative Time: Within 28 days after treatmentDescription: The duration of a fever above 37.3 degrees Celsius
Measure: Duration of fever (Celsius) Time: Within 28 days after treatmentDescription: Marker for efficacy
Measure: Changes of blood oxygen (%) Time: Within 28 days after treatmentDescription: Marker for efficacy
Measure: Rate of all-cause mortality within 28 days Time: Within 28 days after treatmentDescription: Counts of lymphocyte in a litre (L) of blood
Measure: Lymphocyte count (*10^9/L) Time: Within 28 days after treatmentDescription: Alanine aminotransferase in unit (U)/litre(L)
Measure: Alanine aminotransferase (U/L) Time: Within 28 days after treatmentDescription: Creatinine in micromole (umol)/litre(L)
Measure: Creatinine (umol/L) Time: Within 28 days after treatmentDescription: Creatine kinase in U/L
Measure: Creatine kinase (U/L) Time: Within 28 days after treatmentDescription: C-reactive in microgram (mg)/litre(L)
Measure: C-reactive protein (mg/L) Time: Within 28 days after treatmentDescription: Procalcitonin in nanogram (ng)/litre(L)
Measure: Procalcitonin (ng/L) Time: Within 28 days after treatmentDescription: Lactate in millimole(mmol)/litre(L)
Measure: Lactate (mmol/L) Time: Within 28 days after treatmentDescription: IL-1beta in picogram(pg)/millilitre(mL)
Measure: IL-1beta (pg/mL) Time: Within 28 days after treatmentDescription: IL-2 in pg/mL
Measure: IL-2 (pg/mL) Time: Within 28 days after treatmentDescription: IL-6 in pg/mL
Measure: IL-6 (pg/mL) Time: Within 28 days after treatmentDescription: IL-8 in pg/mL
Measure: IL-8 (pg/mL) Time: Within 28 days after treatmentWhereas 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.
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.
Description: Presence of recovery of pneumonia characterized by cease of respiratory symptoms
Measure: Recovery of Pneumonia Time: 14 daysDescription: Increment or decrease in mg/ml of C-reactive protein
Measure: Response of C-reactive protein Time: 14 daysDescription: Increment or decrease in ng/ml of ferritin
Measure: Response of Ferritin Time: 14 daysDescription: Increment or decrease in mg/ml of D-dimer
Measure: Response of D-dimer Time: 14 daysDescription: Requirement of Intensive Care Unit on the patients under treatment
Measure: Rate of ICU admission Time: 14 daysDescription: Requirement of mechanical ventilation on the patients under treatment
Measure: Rate of mechanical ventilation Time: 14 daysDescription: Time since the diagnosis to the last follow up (recovery or death)
Measure: Overall Survival Time: 1 monthDescription: Rate of adverse events associated with ruxolitinib
Measure: Toxicity Rate Time: 1 monthRationale: 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.
Description: Death is defined as all-cause mortality
Measure: first occurrence of intensive care unit admission, mechanical ventilation or death Time: within 14 daysDescription: All-cause mortality; and time to all-cause mortality
Measure: Death Time: Within 14 days, 30 days, 90 days and at 1 yearDescription: Occurrence of mechanical ventilation and time to ventilation
Measure: Mechanical ventilation Time: within 14 daysDescription: Occurrence of ICU admission and time to admission
Measure: Intensive care unit admission Time: within 14 daysDescription: 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 daysThis 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).
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 randomizationDescription: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization
Measure: Mortality rate Time: after randomization, up to 28 daysDescription: 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 daysDescription: Viral load change in blood and oropharyngeal swab samples
Measure: Viral concentration Time: After randomization, up to 7 daysDescription: Incidence of serious adverse events during and after treatment
Measure: Cumulative incidence of serious adverse events Time: During and after intervention, up to 28 daysDescription: 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 daysDescription: proportion of discontinuation or temporary suspension of treatment (for any reason)
Measure: Proportion of patients with discontinued treatment Time: after randomization, up to 28 daysDescription: proportion of patients with increased levels of troponin I
Measure: Incidence of cardiac lesions Time: after randomization, up to 120 daysDescription: proportion and magnitude of QTcF interval increases higher than 500ms
Measure: Incidence of cardiac disfunctions Time: after randomization, up to 120 daysDescription: Changes measured on day 120 will be compared to baseline, through spirometry.
Measure: Change in respiratory capacity Time: Day 120 after randomizationThis 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).
Description: Mortality rate on day 28, after randomization
Measure: Mortality rate at day 28 Time: on day 28, after randomizationDescription: 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.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.
Description: Mortality rate evaluated 28 days after randomization
Measure: Day-28 mortality Time: 28 days after randomizationDescription: 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 randomizationDescription: Mortality rate evaluated during Intensive care unit stay
Measure: Intensive Care Unit mortality Time: Up to 60 days after randomizationDescription: Mortality rate evaluated 60 days after randomization
Measure: Day-60 mortality Time: 60 days after randomizationDescription: Number of patients with pneumonia diagnosed during intensive care unit stay
Measure: Nosocomial pneumonia Time: Up to 60 days after randomizationDescription: Number of patients with bacteremia diagnosed during intensive care unit
Measure: Bacteremia Time: Up to 60 days after randomizationDescription: Placement of ECMO during intensive care unit stay
Measure: Extra corporeal membrane oxygenation (ECMO) Time: Up to 60days after randomizationDescription: Number of patients who underwent tracheostomy during intensive care unit stay
Measure: Tracheostomy Time: Up to 60 days after randomizationDescription: Number of Prone position session
Measure: Prone Position Time: Up to 60 days after randomizationAs 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.
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 daysDescription: 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 28Description: 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 28Description: Severity scoring of lung oedema on the chest radiograph
Measure: Radiological score Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in mg/L
Measure: Biological efficacy endpoints - C-reactive protein Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in microgram/L
Measure: Biological efficacy endpoints - Procalcitonin Time: Days 1, 3, 7, 14, 21 and 28Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: Up to 28 daysDescription: Use of corticosteroids, antiretroviral, chloroquine
Measure: Number of patients using other treatments for COVID-19 related ARDS Time: Up to 28 daysDescription: 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 daysDescription: 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 daysDescription: Medical research council sum score on awakening
Measure: Occurrence of critical illness neuromyopathy Time: Up to 28 daysDescription: 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 daysThe 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.
Description: no unit
Measure: Recruitment-to Inflation ratio (R/I ratio) Time: Day 1Description: no unit
Measure: Recruitment-to Inflation ratio (R/I ratio) Time: Day 5Description: no unit
Measure: Recruitment-to Inflation ratio (R/I ratio) Time: Day 10Description: Arterial blood gases
Measure: PaO2/FiO2 (mmHg) Time: Day 1Description: Arterial blood gases
Measure: PaO2/FiO2 (mmHg) Time: Day 5Description: Arterial blood gases
Measure: PaO2/FiO2 (mmHg) Time: Day 10Description: mL
Measure: Lung volume recruited (VRec) Time: Day 1Description: mL
Measure: Lung volume recruited (VRec) Time: Day 5Description: mL
Measure: Lung volume recruited (VRec) Time: Day 10Description: Obtained by inspiratory pause of 5 seconds
Measure: Plateau pressure (cm H2O) Time: Day 1Description: Obtained by inspiratory pause of 5 seconds
Measure: Plateau pressure (cm H2O) Time: Day 5Description: Obtained by inspiratory pause of 5 seconds
Measure: Plateau pressure (cm H2O) Time: Day 10Description: Obtained by expiratory pause of 5 seconds
Measure: PEEP total (cm H2O) Time: Day 1Description: Obtained by expiratory pause of 5 seconds
Measure: PEEP total (cm H2O) Time: Day 5Description: Obtained by expiratory pause of 5 seconds
Measure: PEEP total (cm H2O) Time: Day 10Description: 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 1Description: 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 5Description: 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 10Description: 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 1Description: 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 5Description: 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 10Study 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.
Description: Mortality at Day 43
Measure: Primary endpoint Time: 43 daysDescription: Subjects who die will be assigned "0" ventilator-free days
Measure: Number of ventilator-free days. Time: Day 43This 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.
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 7This protocol provides access to eculizumab treatment for participants with severe COVID-19.
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).
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 5Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 90 daysDescription: 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 daysDescription: 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 earlierDescription: 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 daysDescription: Measuring respiratory mechanics in ventilated patients [plateau pressure (Pplat)-positive end-expiratory pressure]
Measure: Plat-PEEP Time: 28 daysDescription: 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 daysDescription: 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 daysDescription: As assessed via serum blood samples.
Measure: C-Reactive Protein levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: D-dimer levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: 25-Hydroxy Vitamin D levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Alloantibodies levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Blood white cell count Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Platelets count Time: Baseline, 28 daysThe 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.
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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 48 hour mortality for hospitalized patients
Measure: 48 hour in-hospital mortality Time: at 48 hours post randomizationDescription: 14 days mortality for hospitalized patients
Measure: 14 days in-hospital mortality Time: 14 days post randomizationDescription: 28 days mortality for hospitalized patients
Measure: 28 days in-hospital mortality Time: 28 days post randomizationDescription: 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 extubationDescription: 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 paralyticsDescription: 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)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
Description: (Presence/Absence) requirement of mechanical ventilation
Measure: Mechanical ventilation Time: expected within first three days (non conclusive due to lack of evidence yet)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 sedationThe 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.
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 positioningDescription: Changes in intrapulmonary shunt fraction
Measure: Intrapulmonary shunt Time: One hour before turning to prone or supine positioningDescription: Changes in the phase three slope of the volumetric capnogram
Measure: Volumetric capnography Time: One hour before turning to prone or supine positioningIt 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: every 24 hours fibrinogen value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - fibrinogen Time: 15 daysDescription: every 24 hours transaminases value in U/L
Measure: Evaluation of known adverse events related to the use of the drug - transaminases Time: 15 daysDescription: every 24 hours aPTT value in seconds
Measure: Evaluation of known adverse events related to the use of the drug - aPTT Time: 15 daysDescription: every 24 hours INR value in %
Measure: Evaluation of known adverse events related to the use of the drug - INR Time: 15 daysDescription: every 24 hours glycemia value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - glycemia Time: 15 daysDescription: 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 daysDescription: Total leucocyte as CBC x10e)/L
Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes count Time: 15 daysDescription: formula % on total leucocyte
Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes formula Time: 15 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Number of AE grade 1 to 4
Measure: Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy Time: 15 daysIdeal 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.
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 monthDescription: 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 monthDescription: 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 monthDescription: 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 monthDescription: Count of participants who die from COVID-19
Measure: Mortality Time: up to 1 month post hospital dischargeDescription: Length of hospital stay in days
Measure: Length of hospital stay Time: up to 1 monthDescription: Count of patients admitted to the ICU at any time during index hospitalization
Measure: Intensive Care Unit (ICU) admission Time: up to 1 monthDescription: Length of ICU stay in days
Measure: Intensive Care Unit (ICU) duration Time: up to 1 monthDescription: Count of participants requiring intubation
Measure: Intubation Time: up to 1 monthDescription: Length of intubation, measured in days
Measure: Intubation duration Time: up to 1 monthDescription: Time measured in days from hospital admission to determination patient is stable for discharge
Measure: Time until recovery Time: up to 1 monthThe 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).
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.
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.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.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.
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.
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 daysAcute 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.
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 3Description: 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 3Description: 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 3This study compare the efficacy and safety of tocilizumab versus methylprednisolone in the cytokine release syndrome of patients with COVID-19
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 randomizationDescription: Improvement in PaO2/FIO2
Measure: Improving oxygenation Time: 15 daysDescription: Improvement in the computed tomography between D0 and D10 after randomization
Measure: Thorax CT improvement Time: 10 daysDescription: Duration o ICU stay in days
Measure: ICU length of stay Time: 28 daysDescription: Days of mechanical ventilation
Measure: Duration of mechanical ventilation Time: 28 daysDescription: AKI according to Kidney Disease Improving Global Outcomes (KDIGO)
Measure: Incidence of acute kidney (AKI) with necessity of renal replacement therapy Time: 15 daysThe 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.
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 monthsDescription: 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 monthsDescription: 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 monthsDescription: 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 monthsDescription: 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 monthsThe 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).
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 inclusionDescription: All-cause mortality
Measure: All-cause mortality Time: Days 7, 14, and 28 after inclusionDescription: 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 inclusionDescription: Number of days alive and not in the ICU from inclusion to day 28
Measure: ICU-free days Time: Day 28 after inclusionDescription: Total duration of controlled mechanical ventilation to day 28
Measure: Duration of invasive mechanical ventilation Time: Day 28 after inclusionDescription: Total duration of controlled mechanical ventilation to day 28
Measure: Duration of controlled mechanical ventilation Time: Day 28 after inclusionDescription: 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 inclusionDescription: Partial pressure of arterial carbon dioxide (PaCO2)
Measure: Physiological measures of lung function Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusionDescription: Inspiratory plateau pressure
Measure: Physiological measures of lung function Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusionDescription: Driving pressure
Measure: Physiological measures of lung function Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusionDescription: Mode of mechanical ventilation (assisted versus controlled)
Measure: Physiological measures of lung function Time: Days 1, 2, 3, 4, 5, 6, and 7 from inclusionDescription: 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 inclusionDescription: Development of pneumothorax
Measure: Development of complications Time: Day 7 from inclusionDescription: Supraventricular tachycardia
Measure: Development of complications Time: Day 7 from inclusionDescription: New onset atrial fibrillation
Measure: Development of complications Time: Day 7 from inclusionDescription: Total duration (in days) of vasopressor use
Measure: Duration of vasopressor use Time: Day 28 after inclusionDescription: Total duration (in days)of renal replacement therapy
Measure: Duration of renal replacement therapy Time: Day 28 after inclusionDescription: 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 inclusionDescription: Number of days with continuous neuromuscular blockade
Measure: Duration of continuous neuromuscular blockade Time: Day 28 from inclusionDescription: Sedation drug(s) used (name(s))
Measure: Type of sedation practices Time: Day 28 from inclusionDescription: Number of days with sedation
Measure: Duration of sedation practices Time: Day 28 from inclusionDescription: If inhaled sedation, device used to deliver it
Measure: Modalities of sedation practices Time: Day 28 from inclusionRenal 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)
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.
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 monthsDescription: 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 monthsDescription: 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 collectionTo 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).
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 29Description: Improvement on the WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale)
Measure: WHO clinical Improvement Time: Day15 Day 22 and Day 29Description: Proportion of subjects with normalization of fever and oxygen saturation through
Measure: Normalization of Fever and Oxygen Time: Day 15, Day 22, and Day 29Description: Percentage of subjects discharged from hospital
Measure: Discharge from Hospital Time: Day 15 and Day 22Description: Proportion of patients alive and free of respiratory failure
Measure: Patients alive and free of respiratory failure Time: Day 15, and Day 22Randomized, 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.
Description: Number of patients who died, by treatment group
Measure: All-cause mortality at day 28 Time: Day 28Description: Number of patients with treatment-emergent adverse events, by treatment group
Measure: Safety of WJ-MSC Time: Day 28Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group
Measure: Need for treatment with rescue medication Time: Day 28Description: 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 28Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.
Measure: Ventilator free days Time: Day 28Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.
Measure: Evolution of PaO2 / FiO2 ratio Time: Day 28Description: 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 28Description: 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 28Description: 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 28Description: 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 28Description: 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 28Description: 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 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: D-dimer Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: Ferritin Time: Day 28Description: Blood sample analysis
Measure: Analysis of subpopulations of lymphocytes and immunoglobulins Time: Day 28Description: 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 28Description: Reactivity will be assessed using ELISPOT
Measure: Study of reactivity against SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis
Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis for the patient's genomic sequencing
Measure: Genetic variability of patient's genotype in response to treatment Time: Day 28Description: 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 28Recent 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.
Description: Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.
Measure: Intergroup mortality difference with treatment Time: 28 days.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 daysDescription: 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 daysDescription: 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 daysDescription: 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 dischargeDescription: 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 dischargeDescription: 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 dischargeDescription: 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 dischargeDescription: 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 dischargeDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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.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 monthsDescription: 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 monthsDescription: 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 monthsDescription: 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 monthsCOVID-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.
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 dischargeDescription: 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 dischargeDescription: 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 dischargeDescription: 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.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.
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 randomizationDescription: Daily evolution of oxygenation
Measure: Oxygenation (SpO2/FiO2 ratio) Time: Until HFNC weaning, or up to 14 days after randomization, whichever is firstThe 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.
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 daysDescription: 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 44Description: 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 44The 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).
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-infusionDescription: Number of Participants alive by Day 28
Measure: Number of Participants alive by Day 28 Time: Day 28Description: Number of Participants with ventilator-free Days by Day 28
Measure: Number of Participants with ventilator-free Days by Day 28 Time: Day 28