Covid 19 Research using Clinical Trials (Home Page)
PlacebosWiki
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Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation
Correlated Drug Terms (34)
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug1331 | Leronlimab (700mg) Wiki | 0.34 |
| drug1444 | Mavrilimumab Wiki | 0.28 |
| drug2540 | Toraymyxin PMX-20R (PMX Cartridge) Wiki | 0.24 |
| drug2871 | lopinavir/ritonavir Wiki | 0.24 |
| drug2006 | RS blend Wiki | 0.24 |
| drug700 | DAS181 OL Wiki | 0.24 |
| drug2611 | Use of virus (Covid-19) genome sequence report to inform infection prevention control procedures Wiki | 0.24 |
| drug2015 | RTB101 Wiki | 0.24 |
| drug517 | Canakinumab Injection 600mg Wiki | 0.24 |
| drug167 | Anakinra and Zinc Wiki | 0.24 |
| drug783 | Dociparastat sodium Wiki | 0.24 |
| drug1519 | Montelukast Oral Granules Wiki | 0.24 |
| drug1031 | HOME-CoV rule implementation Wiki | 0.24 |
| drug172 | Angiotensin 1-7 Wiki | 0.24 |
| drug1447 | Measles-Mumps-Rubella Vaccine Wiki | 0.24 |
| drug516 | Canakinumab Injection 300mg Wiki | 0.24 |
| drug1070 | Honey Wiki | 0.24 |
| drug1682 | On-Line Survey Wiki | 0.24 |
| drug699 | DAS181 COVID-19 Wiki | 0.24 |
| drug1022 | HB-adMSCs Wiki | 0.17 |
| drug1230 | Interleukin-7 Wiki | 0.17 |
| drug751 | Dexamethasone injection Wiki | 0.17 |
| drug1952 | Pulmozyme Wiki | 0.17 |
| drug1595 | Nigella Sativa / Black Cumin Wiki | 0.17 |
| drug2766 | blood samples Wiki | 0.17 |
| drug1898 | Prednisone Wiki | 0.11 |
| drug698 | DAS181 Wiki | 0.10 |
| drug1374 | Losartan Wiki | 0.09 |
| drug1822 | Placebo Wiki | 0.07 |
| drug1103 | Hydroxychloroquine Sulfate Wiki | 0.07 |
| drug923 | Favipiravir Wiki | 0.06 |
| drug2527 | Tocilizumab Wiki | 0.05 |
| drug262 | Azithromycin Wiki | 0.04 |
| drug1086 | Hydroxychloroquine Wiki | 0.02 |
Correlated MeSH Terms (24)
| Name (Synonyms) | Correlation | |
|---|---|---|
| D012772 | Shock, Septic NIH | 0.24 |
| D019446 | Endotoxemia NIH | 0.24 |
| D009410 | Nerve Degeneration NIH | 0.24 |
| D004660 | Encephalitis NIH | 0.24 |
| D006505 | Hepatitis NIH | 0.24 |
| D006506 | Hepatitis A NIH | 0.24 |
| D006519 | Hepatitis, Alcoholic NIH | 0.24 |
| D008457 | Measles NIH | 0.14 |
| D018184 | Paramyxoviridae Infections NIH | 0.14 |
| D003428 | Cross Infection NIH | 0.14 |
| D001249 | Asthma NIH | 0.12 |
| D018805 | Sepsis NIH | 0.11 |
| D008231 | Lymphopenia NIH | 0.11 |
| D012769 | Shock, NIH | 0.10 |
| D007249 | Inflammation NIH | 0.10 |
| D003141 | Communicable Diseases NIH | 0.08 |
| D018352 | Coronavirus Infections NIH | 0.07 |
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.06 |
| D007239 | Infection NIH | 0.05 |
| D055370 | Lung Injury NIH | 0.05 |
| D012141 | Respiratory Tract Infections NIH | 0.05 |
| D011014 | Pneumonia NIH | 0.04 |
| D055371 | Acute Lung Injury NIH | 0.02 |
| D012128 | Respiratory Distress Syndrome, Adult NIH | 0.02 |
Correlated HPO Terms (8)
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0002383 | Encephalitis HPO | 0.24 |
| HP:0012115 | Hepatitis HPO | 0.24 |
| HP:0002180 | Neurodegeneration HPO | 0.24 |
| HP:0002099 | Asthma HPO | 0.12 |
| HP:0100806 | Sepsis HPO | 0.11 |
| HP:0001888 | Lymphopenia HPO | 0.11 |
| HP:0011947 | Respiratory tract infection HPO | 0.05 |
| HP:0002090 | Pneumonia HPO | 0.04 |
There are 17 clinical trials
Clinical Trials
1 A Multicenter, Randomized, Double Blinded, Placebo-controlled Clinical Trial of Anakinra (Plus Zinc) or Prednisone in Patients With Severe Alcoholic Hepatitis by the AlcHepNet Consortium
This multicenter, randomized, double blinded, placebo-controlled clinical trial is focused on novel treatments for severe alcoholic hepatitis (AH), a life-threatening stage of alcoholic liver injury that has a short-term mortality rate much higher than that of other liver diseases. The primary objective of the study is to determine the clinical efficacy and safety of Anakinra (plus zinc) compared to the current standard medical treatment consisting of prednisone in participants with clinically severe AH. Key secondary objectives broadly are as follows: (a) to evaluate the use of biomarkers to assess disease severity and treatment response; and (b) to develop novel endpoints to overcome the limitations of current assessment strategies for severe AH.
NCT04072822 Alcoholic Hepatitis Drug: Anakinra and Zinc Drug: Prednisone Drug: Placebos MeSH:Hepatitis A Hepatitis Hepatitis, Alcoholic
HPO:Hepatitis
Primary Outcomes
Description: The primary analysis will be comparisons of 90-day mortality of Prednisone and Anakinra plus zinc vs Prednisone.
Measure: Survival at 90 days Time: 90 days
Secondary Outcomes
Description: Score will be calculated using the following website: https://www.mdcalc.com/lille-model-alcoholic-hepatitis
(exp(-R))/(1 + exp(-R))
where the variables are as follows:
R = 3.19 - 0.101*(age, years) + 0.147*(albumin day 0, g/L) + 0.0165* (evolution in bilirubin level, µmol/L) - 0.206*(renal insufficiency) - 0.0065*(bilirubin day 0, µmol/L) - 0.0096*(PT, sec)
Renal insufficiency = 1 (if Cr >1.3 mg/dL (115 µmol/L)) or 0 (if ≤1.3 mg/dL (115 µmol/L))
Measure: Changes is Lille score Time: 7, 30, and 90 days
Description: The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
Measure: Changes in MELD score Time: 7, 30, and 90 days
Description: Increase in creatinine of 50% above baseline over a period of 7 days
Increase in creatinine of 0.3 mg/dl within a period of 48 hrs
Onset of renal failure requiring dialysis
Measure: Progression of the development of AKI (acute kidney injury) Time: 7, 30, and 90 days
Description: Defined as failure ≥2 organs
Measure: Progression of the development of multi-organ failure Time: 7, 30, and 90 days
Description: Defined as two or more abnormalities in temperature, increased heart rate, respiration, or white blood cell count with increase in SOFA score ≥2 points
Measure: Progression of the development of SIRS (Systemic Inflammatory Response Syndrome) Time: 7, 30, and 90 days
Description: Recording the change of hospital word from regular floor to ICU floor as a marker for worsening illness and care escalation
Measure: Number of Transfers to ICU Time: 7, 30, and 90 days
Description: New onset of ascites if not present on admission to study
New onset of variceal hemorrhage
New onset of hepatic encephalopathy (HE).
Measure: Rate of changes in liver function Time: 7, 30, and 90 days
Description: The SOFA score will be modified and re-evaluated without platelet counts given that these are usually low in AH.
Measure: Measure of changes in sequential organ failure Assessment (SOFA) scores and proportions requiring hemodynamic support for MAP < 65 mm Hg and lactate > 2 mmol/l, renal replacement therapy or mechanical ventilation. Time: 180 days
Description: Pneumonia defined as new infiltrate by CXR or Chest CT scan not explained by "fluid overload"
Positive blood cultures for bacteria or fungus, not suspected as contaminant
Positive urine fungal culture > 50,000 colonies/ml
Positive urine bacterial culture > 100,000 colonies/ml (mixed flora is excluded)
Soft tissue or bone infections including cellulitis or abscess documented by exam or scan
CNS infection defined as positive culture of CSF or > 5 WBC/ml
Ascitic fluid white cell count >500/ml or neutrophils>250/ml. with or without positive bacterial or fungal cultures
Measure: Measuring the types of infections Time: 180 days
Description: Life-threatening organ dysfunction caused by a dysregulated host response to infection
An increase in SOFA score of 2 points of more
Note: most participants with severe AH have 4 points based on bilirubin only
Measure: Rate of the progression of sepsis Time: 180 days
Description: Defined by a creatinine > 2 mg/dl
Measure: Rate of the progression of renal dysfunction Time: 180 days
Description: Proportion of participants requiring transfer to ICU for care, intubation for airway control, need for ventilator support or RRT.
Measure: Need for care escalation Time: 180 days
Measure: Indicators of gut permeability Time: 180 days
Measure: Survival Time: 30 days and 180 days
2 Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic (COVID MED Trial)
Primary Outcomes
Description: The primary analysis will be comparisons of 90-day mortality of Prednisone and Anakinra plus zinc vs Prednisone.
Measure: Survival at 90 days Time: 90 daysSecondary Outcomes
Description: Score will be calculated using the following website: https://www.mdcalc.com/lille-model-alcoholic-hepatitis (exp(-R))/(1 + exp(-R)) where the variables are as follows: R = 3.19 - 0.101*(age, years) + 0.147*(albumin day 0, g/L) + 0.0165* (evolution in bilirubin level, µmol/L) - 0.206*(renal insufficiency) - 0.0065*(bilirubin day 0, µmol/L) - 0.0096*(PT, sec) Renal insufficiency = 1 (if Cr >1.3 mg/dL (115 µmol/L)) or 0 (if ≤1.3 mg/dL (115 µmol/L))
Measure: Changes is Lille score Time: 7, 30, and 90 daysDescription: The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
Measure: Changes in MELD score Time: 7, 30, and 90 daysDescription: Increase in creatinine of 50% above baseline over a period of 7 days Increase in creatinine of 0.3 mg/dl within a period of 48 hrs Onset of renal failure requiring dialysis
Measure: Progression of the development of AKI (acute kidney injury) Time: 7, 30, and 90 daysDescription: Defined as failure ≥2 organs
Measure: Progression of the development of multi-organ failure Time: 7, 30, and 90 daysDescription: Defined as two or more abnormalities in temperature, increased heart rate, respiration, or white blood cell count with increase in SOFA score ≥2 points
Measure: Progression of the development of SIRS (Systemic Inflammatory Response Syndrome) Time: 7, 30, and 90 daysDescription: Recording the change of hospital word from regular floor to ICU floor as a marker for worsening illness and care escalation
Measure: Number of Transfers to ICU Time: 7, 30, and 90 daysDescription: New onset of ascites if not present on admission to study New onset of variceal hemorrhage New onset of hepatic encephalopathy (HE).
Measure: Rate of changes in liver function Time: 7, 30, and 90 daysDescription: The SOFA score will be modified and re-evaluated without platelet counts given that these are usually low in AH.
Measure: Measure of changes in sequential organ failure Assessment (SOFA) scores and proportions requiring hemodynamic support for MAP < 65 mm Hg and lactate > 2 mmol/l, renal replacement therapy or mechanical ventilation. Time: 180 daysDescription: Pneumonia defined as new infiltrate by CXR or Chest CT scan not explained by "fluid overload" Positive blood cultures for bacteria or fungus, not suspected as contaminant Positive urine fungal culture > 50,000 colonies/ml Positive urine bacterial culture > 100,000 colonies/ml (mixed flora is excluded) Soft tissue or bone infections including cellulitis or abscess documented by exam or scan CNS infection defined as positive culture of CSF or > 5 WBC/ml Ascitic fluid white cell count >500/ml or neutrophils>250/ml. with or without positive bacterial or fungal cultures
Measure: Measuring the types of infections Time: 180 daysDescription: Life-threatening organ dysfunction caused by a dysregulated host response to infection An increase in SOFA score of 2 points of more Note: most participants with severe AH have 4 points based on bilirubin only
Measure: Rate of the progression of sepsis Time: 180 daysDescription: Defined by a creatinine > 2 mg/dl
Measure: Rate of the progression of renal dysfunction Time: 180 daysDescription: Proportion of participants requiring transfer to ICU for care, intubation for airway control, need for ventilator support or RRT.
Measure: Need for care escalation Time: 180 daysMeasure: Indicators of gut permeability Time: 180 days
Measure: Survival Time: 30 days and 180 days
Although a number of therapeutics are being utilized by clinicians to treat patients with COVID-19, none have been systematically evaluated in clinical trials. Lopinavir/ritonavir, an antiretroviral medication, showed equivocal but possibly positive efficacy and safety in a RCT conducted in China and published in NEJM in March of 2020. Hydroxychloroquine, an antimalarial and anti-inflammatory medication, has shown potent antiviral activity in vitro and elimination of viral shedding in a small pilot clinical trial. Losartan, an angiotensin II receptor blocker (ARB), has theoretical benefit as SARSCoV-2 appears to bind to lung tissue via Angiotensin-Converting Enzyme 2 (ACE-2) receptors which might be inhibited by ARBs. This pragmatic adaptive trial compares outcome in COVID-19 patients treated with lopinavir/ritonavir, hydroxychloroquine, losartan, and placebo.
NCT04328012 SARS-CoV-2 Infection Drug: lopinavir/ritonavir Drug: Hydroxychloroquine Sulfate Drug: Losartan Drug: Placebos
Primary Outcomes
Description: difference in NCOSS scores between the different treatment groups
Measure: National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS) Time: 60 daysSecondary Outcomes
Description: difference in the total inpatient LOS between the four treatment groups
Measure: Hospital length of stay (LOS) Time: 60 daysDescription: difference in the total ICU level care LOS between the four treatment groups
Measure: Intensive care unit level LOS Time: 60 daysDescription: difference in length of use of mechanical ventilation between the four treatment groups
Measure: Mechanical ventilation Time: 60 daysDescription: difference in all cause mortality between the four treatment groups
Measure: survival Time: 60 days3 Pre-Exposure Prophylaxis With Hydroxychloroquine for High-Risk Healthcare Workers During the COVID-19 Pandemic: A Multicentre, Double-Blinded Randomized Controlled Trial
The investigators aim to evaluate the efficacy of pre-exposure prophylaxis with hydroxychloroquine in healthcare workers with high-risk of SARS-CoV-2 infection.
NCT04331834 COVID-19 Drug: Hydroxychloroquine Drug: Placebos
Primary Outcomes
Description: Confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative PCR for SARS-CoV-2 on day 0 and negative serology for SARS-CoV-2 on day 0.
Measure: Confirmed cases of a COVID-19 Time: Up to 6 months after start of treatmentSecondary Outcomes
Description: SARS-CoV-2 seroconversion in the PrEP group compared to placebo in during 6 months of follow-up in healthcare workers with negative serology at day 0.
Measure: SARS-CoV-2 seroconversion Time: Up to 6 months after start of treatmentDescription: Incidence of clinical and/or laboratory adverse events will be compared in the PrEP group and in the placebo arm.
Measure: Occurrence of any adverse event related with hydroxychloroquine treatment Time: Up to 6 months after start of treatmentDescription: Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers will be estimated by the number of healthcare workers diagnosed with COVID-19 in the placebo group, among the total of healthcare workers included in the non-PrEP group during the study period.
Measure: Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers Time: Up to 6 months after start of treatmentMeasure: Risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19 Time: Up to 6 months after start of treatment
Description: A repository (biobank) of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection.
Measure: COVID-19 Biobank Time: Up to 6 months after start of treatment4 Azithromycin for Prevention of Disease Progression in Patients With Mild or Moderate COVID-19
This individually randomized telemedicine-based trial aims to evaluate the efficacy of a single dose of azithromycin for prevention of progression of COVID-19 in patients with a recent positive SARS-CoV-2 test who are not currently hospitalized.
NCT04332107 COVID-19 SARS-CoV-2 Drug: Azithromycin Drug: Placebos
Primary Outcomes
Description: All-cause hospitalization or emergency room stay of >24 hours
Measure: Hospitalization Time: 14 daysSecondary Outcomes
Description: Viral load by self-collected nasal swab
Measure: Viral load Time: 3 daysDescription: Viral load by self-collected saliva swab
Measure: Viral load Time: 3 daysDescription: All-cause mortality
Measure: Mortality Time: 14 daysDescription: Proportion of participants experiencing adverse events, including gastrointestinal side effects and rash
Measure: Adverse events Time: 3 daysDescription: Prevalence of positive SARS-CoV-2 test by self-collected nasal swab
Measure: Positive SARS-CoV-2 test - nasal swab Time: 3 daysDescription: Prevalence of positive SARS-CoV-2 test by self-collected saliva swab
Measure: Positive SARS-CoV-2 test - saliva swab Time: 3 daysDescription: Prevalence of positive SARS-CoV-2 test by self-collected rectal swab
Measure: Positive SARS-CoV-2 test - rectal swab Time: 3 daysDescription: Prevalence of genetic macrolide resistance determinants by self-collected rectal swab
Measure: Genetic macrolide resistance determinants Time: 3 daysDescription: Prevalence of cough, fever, myalgia, anosmia, shortness of breath, fatigue, conjunctivitis, and orthostatic symptoms
Measure: COVID-19 symptoms Time: 3, 7, 14, 21 daysDescription: Number of emergency room visits <24 hours
Measure: Number of emergency room visits Time: 14 daysDescription: Number of household members with confirmed or symptomatic COVID-19
Measure: Number of household members with COVID-19 (confirmed or symptomatic) Time: 14 daysDescription: Deaths within the study will be attempted to be matched with the US National Death Index
Measure: Death Time: 21 days5 Angiotensin-(1,7) Treatment in COVID-19: the ATCO Trial
Background: A novel Coronavirus (SARS-CoV-2) described in late 2019 in Wuhan, China, has led to a pandemic and to a specific coronavirus-related disease (COVID-19), which is mainly characterized by a respiratory involvement. While researching for a vaccine has been started, effective therapeutic solutions are urgently needed to face this threaten. The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter host 's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also play a key role in the modulation of the inflammatory response that characterizes the lung involvement. Angiotensin-(1-7) is a peptide that is downregulated in COVID-19 patient and it may potentially improve respiratory function in this setting. Methods/Design: The Investigators describe herein the methodology of a randomized, controlled, adaptive Phase II/Phase III trial to test the safety, efficacy and clinical impact of the infusion of angiotensin-(1-7) in COVID-19 patients with respiratory failure requiring mechanical ventilation. A first phase of the study, including a limited number of patients (n=20), will serve to confirm the safety of the study drug, by observing the number of the severe adverse events. In a second phase, the enrollment will continue to investigate the primary endpoint of the study (i.e. number of days where the patient is alive and not on mechanical ventilation up to day 28) to evaluate the efficacy and the clinical impact of this drug. Secondary outcomes will include the hospital length of stay, ICU length of stay, ICU and hospital mortality, time to weaning from mechanical ventilation, reintubation rate, secondary infections, needs for vasopressors, PaO2/FiO2 changes, incidence of deep vein thrombosis, changes in inflammatory markers, angiotensins plasmatic levels and changes in radiological findings. The estimated sample size to demonstrate a reduction in the primary outcome from a median of 14 to 11 days is 56 patients, 60 including a dropout rate of 3% (i.e. 30 per group), but a preplanned recalculation of the study sample size is previewed after the enrollment of 30 patients. Expected outcomes/Discussion: This controlled trial will assess the efficacy, safety and clinical impact of the Angiotensin-(1-7) infusion in a cohort of COVID-19 patients requiring mechanical ventilation. The results of this trial may provide useful information for the management of this disease.
NCT04332666 Coronavirus Respiratory Failure Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere SARS-CoV-2 Drug: Angiotensin 1-7 Drug: Placebos MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency
Primary Outcomes
Description: composite outcome of mortality and necessity of mechanical ventilation
Measure: ventilator free days Time: 28 daysSecondary Outcomes
Description: number of days free from intensive care unit
Measure: ICU free days Time: trough study completion, on average 40 daysDescription: Hospital length of stay
Measure: Hospital length of stay Time: through study completion, on average 60 daysDescription: Time to wean from mechanical ventilation
Measure: Time to wean from mechanical ventilation Time: through study completion, on average 14 daysDescription: PaO2/FiO2 changes during drug administration
Measure: PaO2/FiO2 changes during drug administration Time: 48 hoursDescription: US confirmed deep vein thrombosis
Measure: Deep vein thrombosis incidence Time: through study completion, on average 30 daysDescription: including IL-1, IL-2, IL-6, IL-7, IL-8, IL-10, TNF-alpha, interferon gamma
Measure: Changes in inflammatory markers Time: at randomization, 48 hours after randomization and 72 hours after randomizationDescription: Ang II and Ang-(1-7) plasmatic levels
Measure: RAS effectors levels Time: at randomization, 48 hours after randomization and 72 hours after randomizationDescription: Chest x-ray or CT scan changes
Measure: Radiological findings Time: through study completion, on average 30 daysOther Outcomes
Description: phase 2b = principal safety outcome; phase 3 = secondary outcome
Measure: Rate of serious adverse events Time: study drug administration/day 28 or ICU discharge or death6 A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.
NCT04343651 Coronavirus Disease 2019 Drug: Placebos Drug: Leronlimab (700mg) MeSH:Coronavirus Infections
Primary Outcomes
Description: Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. Higher scores mean a worse outcome.
Measure: Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) Time: Day 14Secondary Outcomes
Measure: Time to clinical resolution (TTCR) Time: Day 14Description: This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). Higher scores mean a worse outcome.
Measure: Change from baseline in National Early Warning Score 2 (NEWS2) Time: Days 3, 7, and 14Measure: Change from baseline in pulse oxygen saturation (SpO2) Time: Days 3, 7, and 14
Description: A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Lower scores mean a worse outcome.
Measure: Change from baseline in the patient's health status on a 7-category ordinal scale Time: Days 3, 7, and 14Measure: Incidence of hospitalization Time: Day 14
Measure: Duration (days) of hospitalization Time: Day 14
Measure: Incidence of mechanical ventilation supply Time: Day 14
Measure: Duration (days) of mechanical ventilation supply Time: Day 14
Measure: Incidence of oxygen use Time: Day 14
Measure: Duration (days) of oxygen use Time: Day 14
Measure: Mortality rate Time: Day 14
Measure: Time to return to normal activity Time: Day 14
Other Outcomes
Measure: Change in size of lesion area by chest radiograph or CT Time: Day 14Measure: Change from baseline in serum cytokine and chemokine levels Time: Days 3, 7, and 14
Measure: Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages Time: Days 3, 7, and 14
Measure: Change from baseline in CD3+, CD4+ and CD8+ T cell count Time: Days 3, 7, and 14
7 A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)
The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease.
NCT04347239 Coronavirus Disease 2019 Drug: Placebos Drug: Leronlimab (700mg) MeSH:Coronavirus Infections
Primary Outcomes
Description: Day 0 refers to the data of randomization/first treatment.
Measure: All-cause mortality at Day 28 Time: Day 28Secondary Outcomes
Description: Day 0 refers to the data of randomization/first treatment.
Measure: All-cause mortality at Day 14 Time: Day 14Description: A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Change in clinical status of subject at Day 14 (on a 7 point ordinal scale) Time: Day 14Description: A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Change in clinical status of subject at Day 28 (on a 7 point ordinal scale) Time: Day 28Description: The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and Serum creatinine
Measure: Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14. Time: Day 148 The Role of Honey and Nigella Sativa in the Management of COVID-19; A Randomized Controlled, Open-label, Add-on Trial in Lahore, Pakistan
To evaluate the effectiveness of Nigella Sativa (1 gm seed powder in a capsule orally) and 30 ml of honey stirred in 250 ml of distilled water 12 hourly till patient becomes asymptomatic or a maximum of 14 days with standard hospital care versus standard hospital care alone with placebo capsule and 250 ml water, in clearing the COVID-19 nucleic acid from throat and nasal swab, lowering disease detrimental effects on HRCT chest/X-ray and severity of symptoms along with duration of hospital stay till day 14th day of follow up and 30 days mortality (primary outcomes).
NCT04347382 Coronavirus Infection Sars-CoV2 Drug: Honey Drug: Nigella Sativa / Black Cumin Drug: Placebos MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: RT-PCR will be done on admission day (0 day) and then after every 4th day for 14 days or till the symptoms resolved and RT-PCR gets negative. RT-PCR will only be shown as positive or negative (as per limitation of Pakistan).
Measure: Days required to get a positive COVID-19 PCR to negative Time: upto max 14 daysDescription: HRCT will be conducted at admission day (0-day) and a total of maximum four CT-scan will be conducted after every 4th day. The minimum and score at which we label covid-19 positive will be 5 and 25 respectively using internationally standard nomenclature as described by Fleischner Society glossary and peer-reviewed literature on viral pneumonia.
Measure: HRCT/ X-ray findings of disease progression Time: upto max 14 daysDescription: Clinically disease progression will be evaluated depending upon the severity of symptoms being classified as mild, moderate and severe.
Measure: Severity of symptoms progression Time: upto max 14 daysDescription: Duration of hospital stay would be categorized as the number of days the patient stayed in the ward during treatment. The date of admission and date of discharge would give us total duration of stay.
Measure: Duration of Hospital Saty Time: upto max 14 dayDescription: 30 days mortality rate in each arm
Measure: 30 day mortality Time: 30 daysSecondary Outcomes
Description: every 4th day oxygen saturation at room air will be checked to evaluate the disease progression
Measure: Oxygen Saturation at room air Time: upto max of 14 daysDescription: Involvement of cardiac complications will be assessed
Measure: Incidence of viral myocarditis Time: upto max 14 daysDescription: Lethal complication like ARDS will be assessed to evaluate disease severity
Measure: Incidence of Acute respiratory Distress Syndrome Time: upto max 14 days9 A Randomized, Double-Blind, Single Center, Efficacy and Safety Study of Allogeneic HB-adMSCs to Provide Immune Support Against COVID-19
Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) to provide immune support against COVID-19. The study purpose is to evaluate the safety and efficacy of five IV infusions of HB-adMSCs in subjects with no signs of COVID-19.
NCT04348435 COVID-19 Drug: HB-adMSCs Drug: Placebos
Primary Outcomes
Description: Number of subjects that must be hospitalized for COVID-19 during the conduct of this study
Measure: Incidence of hospitalization for COVID-19 Time: week 0 through week 26 (end of study)Description: Number of subjects who experience symptoms defined to be associated with COVID-19, such as fever, shortness of breath/difficulty breathing, cough.
Measure: Incidence of symptoms associated with COVID-19 Time: week 0 through week 26 (end of study)Secondary Outcomes
Description: Number of subjects that develop upper/lower respiratory infection with hospitalization criteria
Measure: Absence of upper/lower respiratory infection Time: week 0 through week 26Description: change from baseline in leukocyte differential
Measure: Leukocyte differential Time: weeks 0, 6, 14, 26Description: change from baseline in C Reactive protein
Measure: C Reactive protein Time: weeks 0, 6, 14, 26Description: change from baseline in TNF alpha
Measure: TNF alpha Time: weeks 0, 6, 14, 26Description: change from baseline in IL-6
Measure: IL-6 Time: weeks 0, 6, 14, 26Description: change from baseline in IL-10
Measure: IL-10 Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of glucose in the blood (mg/dL)
Measure: Glucose Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of calcium in the blood (mg/dL)
Measure: Calcium Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of albumin in the blood (g/dL)
Measure: Albumin Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of total protein in the blood (g/dL)
Measure: Total protein Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of sodium in the blood (mol/L)
Measure: Sodium Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)
Measure: Total carbon dioxide Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of potassium in the blood (mmol/L)
Measure: Potassium Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of chloride in the blood (mmol/L)
Measure: Chloride Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of BUN in the blood (mg/dL)
Measure: BUN Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)
Measure: Creatinine Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)
Measure: Alkaline phosphatase Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)
Measure: Alanine aminotransferase Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)
Measure: Total bilirubin Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of white blood cells in the blood (x 10^3/uL)
Measure: white blood cells Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of red blood cells in the blood (x 10^6/uL)
Measure: red blood cells Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)
Measure: hemoglobin Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of level of hematocrit in the blood (%)
Measure: hematocrit Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of mean corpuscular volume in the blood (fL)
Measure: mean corpuscular volume Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of mean corpuscular hemoglobin in the blood (pg)
Measure: mean corpuscular hemoglobin Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of mean corpuscular hemoglobin concentration in the blood (g/dL)
Measure: mean corpuscular hemoglobin concentration Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of red cell distribution width in the blood (%)
Measure: red cell distribution width Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of neutrophils in the blood (%)
Measure: neutrophils Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of lymphocytes in the blood (%)
Measure: Lymphs Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of monocytes in the blood (%)
Measure: Monocytes Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of eosinophils in the blood (%)
Measure: Eosinophils Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of basophils in the blood (%)
Measure: Basophils Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of absolute neutrophils in the blood (x 10^3/uL)
Measure: Absolute neutrophils Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of absolute lymphocytes in the blood (x 10^3/uL)
Measure: Absolute lymphs Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of absolute monocytes in the blood (x 10^3/uL)
Measure: Absolute monocytes Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of absolute eosinophils in the blood (x 10^3/uL)
Measure: Absolute eosinophils Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of absolute basophils in the blood (x 10^3/uL)
Measure: Absolute basophils Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of immature granulocytes in the blood (x 10^3/uL)
Measure: Immature granulocytes Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of platelets in the blood (x 10^3/uL)
Measure: Platelets Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of time for blood to coagulate (seconds)
Measure: Prothrombin time Time: weeks 0, 6, 14, 26Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)
Measure: INR Time: weeks 0, 6, 14, 26Description: Short-form 36 Health Survey; scored on a scale of 0-100; lower score equals more disability
Measure: SF-36 Time: weeks 0, 6, 14, 26Description: Depression module; scores DSM-IV criteria 0-3 to monitor severity of depression
Measure: PHQ-9 Time: weeks 0, 6, 14, 2610 Clinical Study Evaluating the Efficacy of Faviprevir in COVID-19 Treatment
Faviprevir in COVID-19 treatment
NCT04351295 COVID Drug: Favipiravir Drug: Placebos
Primary Outcomes
Description: The total number of patients with viral cure
Measure: Number of patients with viral cure Time: 6 months11 Tocilizumab to Prevent the Progression of Hypoxemic Respiratory Failure in Hospitalized Non-Critically Ill Patients With COVID-19
This is a randomized, double blind, multi-center study to evaluate the effects of tocilizumab compared to placebo on patient outcomes in participants with confirmed SARS-CoV-2 infection and evidence of systemic inflammation. The aim of this study is to test the effect of Tocilizumab on multi-organ dysfunction in a phase 3 randomized controlled trial among hospitalized patients with COVID-19 infection. Specifically, as compared to placebo, we will test whether tocilizumab is associated with a reduction in multi-organ dysfunction among hospitalized COVID-19 adult patients with elevated inflammatory measures. Multi-organ dysfunction will be measured as the incidence of the following composite endpoint (mechanical ventilation, renal replacement therapy, mechanical support, need for inotropes or vasopressors, liver dysfunction (increased bilirubin), and all-cause mortality). We will also assess multiple pre-specified secondary (exploratory) endpoints and safety endpoints. We hypothesize that, as compared to placebo, tocilizumab will reduce transfer to the ICU, need for mechanical ventilation, increase rates of hospital discharge in patients diagnosed with severe COVID-19 infection and evidence of exaggerated inflammatory response.
NCT04356937 SARS-CoV 2 Drug: Tocilizumab Drug: Placebos
Primary Outcomes
Description: The time to event will be the time from administration of the investigational agent (or from randomization if the investigational agent was not administered) to the time of initiation of mechanical ventilation for subjects who are intubated and to the time of death for subjects who die prior to intubation. All subjects who do not have either event by the end of the follow-up period will be censored at 28 days.
Measure: Time to mechanical ventilation or death Time: 28 daysSecondary Outcomes
Description: Time to improvement will be assessed by changes in subjects' status, ranked on the ordinal scale: Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or <= 2L supplemental oxygen) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g. vasopressors, renal replacement therapy) Death Higher scores indicate a worse outcome.
Measure: Time to improvement Time: 28 daysDescription: Time to progression will be measured from the time the investigational medication is administered until the time of progression to non-invasive ventilation or high-flow oxygen. We will compare the groups using a stratified log-rank test and estimate the hazard ratio comparing the groups using a stratified Cox proportional hazards model. For patients requiring non-invasive ventilation or high-flow oxygen at baseline, their time to intubation or death will be assessed for this comparison.
Measure: Time to progression to non-invasive ventilation or high-flow oxygen, defined as >6L Time: 28 daysDescription: The raw ordinal scale scores at days 4, 7, 14, 21, and 28 in subjects treated with tocilizumab therapy versus controls will be compared at each time point using a random intercept proportional odds logistic regression model. This model will be used to model all measurements together to estimate the differences between the treatment groups at each time point.
Measure: Raw ordinal scale scores at days 4, 7, 14, 21, and 28. Time: Days 4, 7, 14, 21, and 28Description: Time to absence of the need for supplemental oxygen will be measured from time of investigational treatment administration. We will use the same approach as that employed for the comparison of time to clinical improvement. Only subjects on supplemental oxygen at the time of randomization will contribute to this analysis. Subjects who die will be censored at 29 days, and the groups will be compared using a stratified log-rank test and stratified Cox proportional hazards model.
Measure: Time to absence of the need for supplemental oxygen Time: 28 daysDescription: The duration of supplemental oxygen will be compared between the groups. For this analysis, we will include all subjects in the analysis by assigning all subjects who did not receive supplemental oxygen a value of 0. Subjects who died following supplemental oxygen will be given a value of the number of days from when supplemental oxygen began until the end of the follow-up period. The groups will be compared using a Wilcoxon rank sum test.
Measure: Duration of supplemental oxygen Time: 28 daysDescription: For time to improvement in the NEWS2 score to ≤ 2 or discharge from the hospital, we will use the same approach as time to clinical improvement. Subjects who die will be censored at the end of the study to indicate that they did not have an improvement event by the end of the study. The groups will be compared using a stratified log-rank test and stratified Cox proportional hazards model.
Measure: Time to improvement in NEWS2 score to ≤ 2 or discharge from the hospital. Time: 28 daysDescription: Time to death will be measured from the time the investigational medication is administered until the time of the subject's death. We will compare the groups using a stratified log-rank test and estimate the hazard ratio comparing the groups using a stratified Cox proportional hazards model.
Measure: Time to death Time: 28 daysDescription: Mortality at 28 days will be compared using a Mantel-Haenszel test to allow stratification on study site. The relative risk will be estimated using the Mantel-Haenszel method. If we have missing mortality data on any subjects, we will estimate the proportion of subjects who died in each treatment group using the estimate from the Kaplan-Meier curve in each group. Then, we will compare the two groups using the approaches described in Klein et al (citation: Klein JP, Logan B, Harhoff M, Anderson PK. Analyzing survival curves at a fixed point in time. Statistics in Medicine. 2007;26:4505-4519.)
Measure: Mortality at 28 days Time: 28 daysDescription: Time to intubation will be measured from time of investigational treatment administration to the time of intubation. For this analysis, death will be treated as a competing risk. The analysis will compare the cause-specific hazard in the treatment groups using a Cox proportional hazards model. We will also compare the cumulative incidence functions between groups using the approach of Fine and Gray.
Measure: Time to intubation Time: 28 daysDescription: The duration of mechanical ventilation will be compared between the groups using two approaches. First, we will include all subjects in the analysis by assigning all subjects who were not intubated a value of 0. Subjects who died following intubation will be given a value of the number of days from when mechanical ventilation began until the end of the follow-up period. The groups will be compared using a Wilcoxon rank sum test. Second, we will analyze only subjects who were intubated and compare the time on mechanical ventilation using a stratified log-rank test. Subjects who die without being taken off the ventilator will be censored at a duration of mechanical ventilation longer than the longest time.
Measure: Duration of mechanical ventilation Time: 28 daysDescription: The proportion of subjects requiring ICU admission between baseline and 28 days will be measured as the number of subjects requiring ICU admission over their hospitalization over the number of evaluable subjects (i.e., the number of subjects not in the ICU at the time of investigational treatment administration). The groups will be compared using a Mantel-Haenszel test to allow stratification on study site. The relative risk will be estimated using the Mantel-Haenszel method.
Measure: Proportion of subjects requiring ICU admission Time: 28 daysDescription: The time to discharge from the hospital in subjects, measured from the time of investigational treatment administration to time of discharge, will be compared using a stratified log-rank test. Subjects who die will be censored at Day 29 to indicate that they never left the hospital during the study.
Measure: Time to discharge Time: 28 daysDescription: Safety and tolerability, defined as adverse events graded by CTCAE v5.0, will be compared using a Mantel-Haenszel test to allow stratification on study site. The relative risk will be estimated using the Mantel-Haenszel method.
Measure: Safety and tolerability Time: 28 days12 Effectiveness of Measles Vaccine in Health Care Professionals During COVID-19 Outbreak (Randomized Controlled Trial)
Till now, mortality reports among children below 9 years remains extremely low despite that the incidence of death toll is high and exceeding 50,000 patients among older population, One speculation for lower SARS infectivity is that cross-protective antibodies against measles vaccine ( MV). In mice susceptible to measles virus, recombinant MV induced the highest titers of neutralizing antibodies and fully protected immunized animals from intranasal infectious challenge with SARS-CoV, The primary objective of the present study is to determine the benefit of measles vaccine in health care professional to decrease the incidence of COVID-19. We Hypothesized that, measles vaccine may lower the incidence of serologically proven SARS-CoV-2 infection and reported respiratory illness
NCT04357028 Covid19 Drug: Measles-Mumps-Rubella Vaccine Drug: Placebos MeSH:Measles
Primary Outcomes
Description: Number of participants with asymptomatic or mild COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: COVID-19 disease incidence Time: Time Frame: Measured over the 6 months following randomizationSecondary Outcomes
Description: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: SARS-CoV-2 pneumonia Time: Time Frame: Measured over the 6 months following randomizationDescription: Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Critical care admission duration with SARS-CoV-2 Time: Time Frame: Measured over the 6 months following randomizationDescription: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Oxygen therapy with SARS-CoV-2 Time: Time Frame: Measured over the 6 months following randomization13 Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
This trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.
NCT04360876 COVID-19 ARDS Drug: Dexamethasone injection Drug: Placebos MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.
Measure: Ventilator Free Days (VFD) at Day 28 Time: 28 Days
Secondary Outcomes
Description: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
Measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale. Time: 14 Days
Measure: Clinical Status at day 28 as measured by WHO 7-point ordinal scale Time: 28 Days
Measure: In-Hospital Mortality at day 28 Time: 28 Days
Measure: In-Hospital Mortality at day 90 Time: 90 Days
Measure: Time to Mortality to day 28 Time: 28 Days
Measure: ICU-free days to day 28 Time: 28 Days
Measure: Hospital Length of Stay among survivors to day 90 Time: 90 Days
Measure: Severity of ARDS to day 10 Time: 10 Days
Measure: Days to resolution of fever Time: 28 Days
Measure: Change in C-Reactive Protein (CRP) level from baseline to day 10 Time: 10 Days
Measure: Vasopressor-free days to day 28 Time: 28 Days
Measure: Renal replacement-free days to day 28 Time: 28 Days
Measure: Duration of mechanical ventilation to day 28 Time: 28 Days
Measure: Oxygenation-free days to day 28 Time: 28 Days
Measure: Incidence of New Mechanical Ventilation to day 28 Time: 28 Days
Measure: Change in sequential organ failure assessment (SOFA) score from baseline to day 10 Time: 10 Days
Measure: In-hospital adverse events to day 28 Time: 28 Days
Measure: Discontinuation of study drug infusion Time: 10 Days
14 Canakinumab to Reduce Deterioration of Cardiac and Respiratory Function in SARSCoV2 Associated Acute Myocardial Injury With Heightened Inflammation
Primary Outcomes
Description: Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.
Measure: Ventilator Free Days (VFD) at Day 28 Time: 28 DaysSecondary Outcomes
Description: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
Measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale. Time: 14 DaysMeasure: Clinical Status at day 28 as measured by WHO 7-point ordinal scale Time: 28 Days
Measure: In-Hospital Mortality at day 28 Time: 28 Days
Measure: In-Hospital Mortality at day 90 Time: 90 Days
Measure: Time to Mortality to day 28 Time: 28 Days
Measure: ICU-free days to day 28 Time: 28 Days
Measure: Hospital Length of Stay among survivors to day 90 Time: 90 Days
Measure: Severity of ARDS to day 10 Time: 10 Days
Measure: Days to resolution of fever Time: 28 Days
Measure: Change in C-Reactive Protein (CRP) level from baseline to day 10 Time: 10 Days
Measure: Vasopressor-free days to day 28 Time: 28 Days
Measure: Renal replacement-free days to day 28 Time: 28 Days
Measure: Duration of mechanical ventilation to day 28 Time: 28 Days
Measure: Oxygenation-free days to day 28 Time: 28 Days
Measure: Incidence of New Mechanical Ventilation to day 28 Time: 28 Days
Measure: Change in sequential organ failure assessment (SOFA) score from baseline to day 10 Time: 10 Days
Measure: In-hospital adverse events to day 28 Time: 28 Days
Measure: Discontinuation of study drug infusion Time: 10 Days
TThe purpose of this prospective, Phase 2, single center, blinded, randomized controlled study is to demonstrate as a proof of concept that early treatment with canakinumab prevents progressive heart and respiratory failure in patients with COVID-19 infection. These results will lead to and inform a Phase III randomized placebo-controlled trial.
NCT04365153 COVID-19 SARS-CoV 2 Drug: Canakinumab Injection 600mg Drug: Canakinumab Injection 300mg Drug: Placebos
Primary Outcomes
Description: Number of days
Measure: Time to clinical improvement up to day 14, defined as the time in days from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever occurs first. Time: Up to day 14Secondary Outcomes
Description: Number of days
Measure: Mortality at day 28 Time: Up to day 2815 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in UK
Comparison of the effects of CYT107 vs Placebo administered IM at 10µg/kg twice a week for two weeks on immune reconstitution of lymphopenic COVID-19 patients.
NCT04379076 COVID-19 Lymphocytopenia Drug: Interleukin-7 Drug: Placebos MeSH:Lymphopenia
HPO:Lymphopenia
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whicheve Time: 1 month
Secondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: To obtain "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: 1 month
Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: one month
Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45 Time: 45 days
Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: To compare the effect of CYT107 versus placebo on the length of hospitalization Time: 45 days
Description: Number of days in ICU during index hospitalization
Measure: To compare the effect of CYT107 versus placebo on the length of stay in ICU Time: 45 days
Description: Readmissions to ICU through Day 45
Measure: To compare the effect of CYT107 versus placebo on readmissions to ICU Time: 45 days
Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.)
Measure: To compare the effect of CYT107 versus placebo on organ support free days Time: 45 days
Description: Number of readmissions to the hospital through Day 45
Measure: To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45 Time: 45 days
Description: All-cause mortality through Day 45
Measure: To assess the impact of CYT107 on all-cause mortality through day 45 Time: 45 days
Description: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
Measure: To determine the effect of CYT107 on CD4+ and CD8+ T cell counts Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: To track and evaluate other known biomarkers of inflammation: Ferritin Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Measure: To track and evaluate other known biomarkers of inflammation: CRP Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: To track and evaluate other known biomarkers of inflammation: D-dimer Time: 30 days
Description: Evaluate improvement of the NEWS2 score value
Measure: Evaluation of physiological status through NEWS2 score Time: 30 days
Other Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)
Measure: Safety assessment Time: 45 days
16 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whicheve Time: 1 monthSecondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: To obtain "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: 1 monthDescription: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: one monthDescription: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45 Time: 45 daysDescription: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: To compare the effect of CYT107 versus placebo on the length of hospitalization Time: 45 daysDescription: Number of days in ICU during index hospitalization
Measure: To compare the effect of CYT107 versus placebo on the length of stay in ICU Time: 45 daysDescription: Readmissions to ICU through Day 45
Measure: To compare the effect of CYT107 versus placebo on readmissions to ICU Time: 45 daysDescription: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.)
Measure: To compare the effect of CYT107 versus placebo on organ support free days Time: 45 daysDescription: Number of readmissions to the hospital through Day 45
Measure: To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45 Time: 45 daysDescription: All-cause mortality through Day 45
Measure: To assess the impact of CYT107 on all-cause mortality through day 45 Time: 45 daysDescription: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
Measure: To determine the effect of CYT107 on CD4+ and CD8+ T cell counts Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: To track and evaluate other known biomarkers of inflammation: Ferritin Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Measure: To track and evaluate other known biomarkers of inflammation: CRP Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: To track and evaluate other known biomarkers of inflammation: D-dimer Time: 30 daysDescription: Evaluate improvement of the NEWS2 score value
Measure: Evaluation of physiological status through NEWS2 score Time: 30 daysOther Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)
Measure: Safety assessment Time: 45 daysThe purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
NCT04399980 COVID 19 SARS-CoV 2 Pneumonia Drug: Mavrilimumab Drug: Placebos MeSH:Pneumonia Respiratory Insufficiency Inflammation
HPO:Pneumonia
Primary Outcomes
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: Day 14
Secondary Outcomes
Description: Number of subjects that are alive
Measure: Proportion of subjects alive at 28 days Time: Day 28
Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: Day 28
17 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation
Primary Outcomes
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: Day 14Secondary Outcomes
Description: Number of subjects that are alive
Measure: Proportion of subjects alive at 28 days Time: Day 28Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: Day 28The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
NCT04463004 COVID-19 Sars-CoV2 Pneumonia Drug: Mavrilimumab Drug: Placebos MeSH:Pneumonia Respiratory Insufficiency Inflammation
HPO:Pneumonia
Primary Outcomes
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: 14 days
Secondary Outcomes
Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: 28 days
Related HPO nodes (Using clinical trials)
HP:0012115: Hepatitis
Genes 91
SERPINA1 RFXANK RFXAP SPIB HSD3B7 CD3D MET TP53 PGM1 IL17F IL17RC BLNK CD79A CD247 STAT1 IL21R FOXP3 IL12RB1 KRT8 FASLG ATP7B IGF2R CYP7A1 CD3E TBX19 BTK RFXANK ALMS1 CASP10 ATP7B C1S GUSB XIAP FAS IL17RA PIK3CA IGHM RASGRP1 MMEL1 TTC7A TCF3 CIITA GPR35 PIK3R1 MST1 CIITA AIRE SLC25A15 TPP2 GLIS3 IRF5 XIAP POU2AF1 C4B VPS33B CYP7B1 SKIV2L BTK PIEZO1 RFX5 TTC7A BTK FAS TNPO3 CD40LG CASP8 ATP7A RFXAP SH2D1A VIPAS39 LRRC8A CTNNB1 PDGFRL CLEC7A SHPK TNFSF15 AXIN1 RFX5 APC PRKCD TCF4 AMACR TRAF3IP2 COG8 ITCH CD79B SLC25A15 IGLL1 KRT18 IL12A COG6 HP:0001888: Lymphopenia
Genes 132
DOCK8 SMARCAL1 ICOS NHEJ1 RAG1 PIK3R1 G6PC3 ELANE PSMB9 WIPF1 IL2RG SRP54 SGPL1 NFKB1 TERT CORO1A STAT1 RAG2 WAS EPG5 IKZF1 PTEN CASP10 EXTL3 FOXN1 UNC119 MS4A1 GATA2 FOXN1 RASGRP1 RAG1 STAT4 CD81 SAMD9 ATM WAS TTC37 SKIV2L ATM CDCA7 TRNT1 CHD7 FOXN1 RAG1 TTI2 DNMT3B CD19 LEP ADAMTS3 ZBTB24 JAK3 PGM3 TNFRSF13B RAG1 STK4 CD3E CTLA4 IRAK1 ICOS CD8A TNFRSF13C TCIRG1 IL7R SEMA3E RFXAP XRCC4 SMARCAL1 MSN RMRP LEPR CTPS1 MYSM1 RAG2 HELLS TINF2 FASLG CD3G SP110 PIK3CD RFXANK CXCR4 FAS ACP5 TERC PTPRC ZAP70 CCBE1 NFKB2 DCLRE1C PSMB4 GFI1 CIITA MTHFD1 TNFSF12 AK2 TPP2 MAGT1 RAG2 TCN2 TFR2 CR2 IL2RA MYC LCK DNMT3B BCL11B DOCK2 CD3D EXTL3 TCF3 NBN NFKB2 ADA IL7R TNFSF12 IGHM TNFAIP3 SPP1 FAS WIPF1 PNP PTEN PRKCD RFX5 PRKCD FAT4 STAT1 ADA CD247 PGM3 IL2RG GFI1 Protein Mutations 0
SNP 0
HP:0002090: Pneumonia
Genes 220
KMT2D OSTM1 GBA RSPH1 DOCK8 NKX2-1 RNU4ATAC SPAG1 RAG1 MCIDAS AFF4 TNFRSF13C DNAH1 NOTCH3 CD19 ALMS1 NADK2 UNC119 SFTPC FOXN1 CD79B CFAP221 CD81 SAMD9 MED25 ZAP70 RAG2 IGLL1 DNAAF1 RPGR STK36 LTBP3 PLOD1 DNAH9 BTK TERT COL11A2 OFD1 TNFRSF11A LRBA RSPH4A CD19 NME8 SMARCD2 GAS8 CFTR TNFRSF13B CCDC65 CFAP298 COL11A2 RAG1 ORC6 P4HTM MAN2B1 CFAP300 JAK3 CACNA1C ICOS SETBP1 TNFRSF13C SPEF2 LIG4 NIPBL STAT3 ZMYND10 IL7R MAN2B1 HLA-DQA1 IL21R SELENON SP110 ACADVL CCDC39 ARMC4 NSMCE3 NFIX DNAI2 ACP5 PTPRC ZAP70 KIAA0586 FCGR2A NFKB2 NEK10 MTHFD1 EGFR RYR1 ADA DNAI1 TGFB1 DNAAF6 IL2RG KCNJ6 DCLRE1C CCDC103 IGHM GNPTAB DNAAF4 PNP CFB DCLRE1C TAF1 CARD11 USB1 ADA ICOS FMO3 IL2RG HLA-DQB1 GFI1 SFTPA2 ICOS CD3D FOXJ1 CRLF1 ELANE IL2RG SRP54 NFKB1 PANK2 GAS2L2 CD247 IRF8 GAS8 RAG2 CCDC151 WAS ZBTB24 CD3E DNAL1 EXTL3 SLC35A1 NCF1 TK2 MS4A1 IFNGR1 RNF168 RMRP RSPH9 NHLRC1 MUC5B TNFRSF13C DNAH5 DNMT3B RNF125 EPM2A TTC12 JAK3 LEP RAC1 CYBA PGM3 NOS1 DDR2 AFF4 TBC1D24 CHD7 TNFRSF13B OFD1 DNAI1 RANBP2 TCIRG1 DNAJB13 CR2 CCDC40 IL2RG NCF2 RAG2 SLC25A24 SGCG WDR19 FOXP3 RNU4ATAC ACTA1 UBB CFAP410 BTK TTC25 CARD11 DNAAF2 CXCR4 MASP2 DRC1 TBCD DCLRE1C CYBB RSPH3 LRRC6 PIGN TNFSF12 DNAAF5 CCNO CSPP1 CR2 SLC35C1 HYDIN TIMM8A NBN NFKB2 CCDC114 CASP8 ADA IL7R CCDC114 TNFSF12 BTK LRRC56 PEPD BLNK CD55 GRHL3 NBN PRKCD KPTN PMM2 DNAAF3 KDM6A POLA1 RAG1 DNAH11 SNP 0
Primary Outcomes
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: 14 daysSecondary Outcomes
Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: 28 days