Correlated Drug Terms (49)

Correlated MeSH Terms (24)

Correlated HPO Terms (5)

Primary Outcomes

Description: CRS will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.

Secondary Outcomes

Description: ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR) through the study (approximately 3 years), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors and Response Evaluation Criteria in Lymphoma (RECIL) for participants with lymphoma.

Description: DOR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Description: DCR is defined as percentage of participants who achieve stable disease (SD) or better greater than (>) 6 weeks during the study in response-evaluable population, as determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Description: PFS will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Description: TTR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Description: Severity Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 5.0.

Description: CRS will be graded as per ASTCT Consensus Grading for CRS.

Description: NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Description: Percentage of participants will be reported based on severity rating on a 6-point ordinal scale, which will include: 1 (death); 2 (hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, hospitalized); 3 (on non-invasive ventilation or high flow oxygen devices); 4 (hospitalized, requiring supplemental oxygen); 5 (hospitalized, not requiring supplemental oxygen); and 6 (not hospitalized).

Description: Change from Baseline in SARS-CoV-2 viral Load in nasopharyngeal or oropharyngeal samples will be determined by viral response. The nasopharyngeal swab will be collected from both nostrils or from the same nostril every time.

Description: Time from the first dose of TAK-981 to viral load negativity (below level of detection).

Description: Time from first dose of TAK-981 to participant's discharge or to NEWS score <=3. NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Primary Outcomes

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

Secondary Outcomes

Description: Measured in days

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

Description: Blood routine test

Description: Oropharyngeal or anal swabs

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

Description: Serum hsCRP

Description: Serum inflammatory cytokines

Description: Flow cytometry for peripheral whole blood

Primary Outcomes

Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.

Secondary Outcomes

Description: Time to an improvement of one category from admission on an ordinal scale. Time to an improvement of two categories from admission on an ordinal scale. Time to discharge (categories 1 or 2 of ordinal scale) from admission. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.

Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.

Description: • Duration of hospitalization (days).

Description: Rate of mortality

Other Outcomes

Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized

Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized

Primary Outcomes

Description: 28-day survival rate, defined by the proportion of patients still alive 28 days after randomization. The 28-day survival rate will be described in each arm of each cohort.

Secondary Outcomes

Description: Time to clinical improvement defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale (WHO-ISARIC) or live discharge from the hospital, whichever comes first.

Description: Clinical status will be assessed using a 7-point ordinal scale : Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.

Description: Mean change in clinical status from baseline will be assessed using a 7-point ordinal scale.

Description: Overall survival will be defined by the time from date of randomization until date of death, regardless of the cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

Description: The length of stay in Intensive Care Unit (from the date of admission in the Unit to the date of discharge).

Description: The duration of mechanical ventilation or high flow oxygen devices (from the date of intubation to the stop date of mechanical ventilation or high flow oxygen)

Description: The duration of hospitalization (from the date of hospitalization to the date of definitive discharge for live patients)

Description: Changes from baseline in neutrophils count (G/L)

Description: Treatment-Emergent Adverse Events, Serious Adverse Events, Suspected Unexpected Serious Adverse Reactions, New Safety Issues described using the NCI-CTC AE classification v5. Number of participants with a discontinuation or temporary suspension of study drugs (for any reason).

Description: Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.

Description: Changes from baseline in lymphocytes count (G/L)

Description: Changes from baseline in platelets count (G/L)

Description: Changes from baseline in hemoglobin count (g/dL)

Description: Changes from baseline in CRP count (mg/L)

Description: Changes from baseline in pro-inflammatory cytokine (IL6)

Primary Outcomes

Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - 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.

Secondary Outcomes

Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - 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.

Primary Outcomes

Description: Number of participants in each arm who expire.

Description: Number of participants in each arm who are hospitalized and requiring mechanical ventilation and/or high flow nasal cannula and/or ICU/CCU admission (or equivalent) and/or ECMO.

Description: Number of participants in each arm who are hospitalized and requiring supplemental oxygen, not requiring ICU/CCU level care (or interventions listed under Outcome 2).

Description: Number of participants in each arm who develop grade 3 and 4 adverse events during the study period.

Description: Number of participants in each arm who develop serious adverse events during the study period.

Description: Number of participants in each arm who develop symptomatic hypotension (systolic blood pressure <90 mmHg) or hypotension requiring cessation of prazosin.

Secondary Outcomes

Description: Number of participants with laboratory abnormalities in peripheral blood (Lymphopenia, leukocytosis, anemia, thrombocytopenia, creatinine, AST/ALT, troponin I, pro-BNP, D-dimer, ferritin, interleukin (IL-6), soluble IL-2 receptor.

Description: Number of days with laboratory abnormalities in peripheral blood (Lymphopenia, leukocytosis, anemia, thrombocytopenia, creatinine, AST/ALT, troponin I, pro-BNP, D-dimer, ferritin, interleukin (IL-6), soluble IL-2 receptor.

Description: Number of participants with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Description: Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Primary Outcomes

Description: At least 3 parameters are met including CRP and/or Ferritin among: CRP: decrease > 50% Ferritinemia: decrease > 1/3 Serum creatinine: decrease > 1/3 AST/ALT: decrease > 50% Eosinophils > 50 /mm3 Lymphocytes > 1000 /mm3

Secondary Outcomes

Description: Number of days without mechanical ventilation

Description: Number of patients included in stage 2b

Description: Number of days in intensive care units for patients managed in intensive care units

Description: Mortality rate

Description: Total number of days in hospital

Description: Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score); Sofa score's minimum and maximum values are 0 and 24, the lowest score corresponds to a better outcome.

Description: Number of bacterial and/or fungal sepsis

Primary Outcomes

Description: Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 28 days of treatment

Secondary Outcomes

Description: Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 14 days of treatment

Description: Percentage of patients death due to any cause at 28 days of treatment

Description: Number of days without mechanical respirator and without vasopressor treatment for 28 days

Description: Percentage of patients alive without mechanical ventilation and without vasopressors on day 28

Description: Percentage of patients alive and without mechanical ventilation on day 14

Description: Percentage of patients alive and without mechanical ventilation on day 28

Description: Percentage of patients alive and without vasopressors on day 28

Description: Number of days without vasopressors for 28 days

Description: Percentage of patients cured at 15 days

Description: Percentage of patients with each adverse event

Primary Outcomes

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Secondary Outcomes

Description: Number of deaths due to all causes will be assessed.

Description: Time to death due to all causes will be assessed.

Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: Time will be recorded from dosing to last dependence on supplementary oxygen. Participants are dependent on supplementary oxygen if they are in category 4 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.

Description: Defined as the time from dosing to when the participant is discharged from the ICU.

Description: Time from dosing to when a participant is discharged from the hospital.

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence, that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.

Primary Outcomes

Description: The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) Death Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT Hospitalized with intubation and mechanical ventilation Hospitalized on non-invasive ventilation or high flow oxygen. Hospitalized on a mask or nasal prongs. Hospitalized no oxygen therapy. Ambulatory, with limitation of activities. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.

Description: Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.

Description: The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.

Secondary Outcomes

Description: Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.

Description: Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.

Description: Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.

Description: Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.

Description: Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.

Primary Outcomes

Description: Proportion of all-cause mortality

Secondary Outcomes

Description: Mean length of stay in intensive care unit

Description: Mean duration of mechanical ventilation

Description: Mean change from baseline using time series analysis

Description: Mean change from baseline using time series analysis

Description: Mean change from baseline using time series analysis

Description: Mean change from baseline using time series analysis

Description: Mean change from baseline using time series analysis

Description: Mean change from baseline using time series analysis

Description: Mean change from baseline using time series analysis

Description: Number of participants with allergic/ anaphylaxis transfusion reaction

Description: Number of participants with Hemolytic transfusion reaction

Description: Number of participants with Transfusion Related Acute Lung Injury

Description: Number of participants with Transfusion associated Circulatory Overload

Primary Outcomes

Description: Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73m^2), haemofiltration or dialysis

Secondary Outcomes

Description: The clinical status of the patients is assessed using 7-point ordinal scale as follows: 1 = Death, 2 = Mechanical ventilation, 3 = Non-invasive or high flow oxygen, 4 = Low flow oxygen, 5 = Hospitalised - no oxygen, 6 = Discharged - normal activities not resumed, 7 = Discharged - normal activities resumed

Description: The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: venous thromboembolism, new infections requiring antimicrobials

Description: The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days

Description: The amount of time between a patient's first positive SARS-CoV2 PCR test and a patient's first negative SARS-CoV2 PCR test, measured in days

Description: The duration of oxygen therapy given to a patient, measured in days

Description: The duration of hospitalisation of a patient, measured in days

Description: The number of deaths recorded at 28 days irrespective of the cause

Description: The time to clinical improvement for a patient, defined as: >2 point improvement from Day 1 on the 7-point ordinal scale, measured in days

Primary Outcomes

Description: Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes/vassopressors) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73m^2), haemofiltration or dialysis

Secondary Outcomes

Description: Change in patient blood levels of IL-6 compared to baseline, measured in pg/mL

Description: Change in patient blood levels of ferritin compared to baseline, measured in ng/mL

Description: Change in patient blood levels of CRP compared to baseline, measured in mg/L

Description: Change in patient blood levels of D-dimer compared to baseline, measured in ng/mL

Description: Change in patient blood levels of neutrophil/lymphocyte ratio compared to baseline

Description: Change in patient blood levels of lactate dehydrogenase (LDH) compared to baseline, measured in U/L

Description: The clinical status of the patients is assessed using 7-point ordinal scale as follows: 1 = Death, 2 = Mechanical ventilation, 3 = Non-invasive or high flow oxygen, 4 = Low flow oxygen, 5 = Hospitalised - no oxygen, 6 = Discharged - normal activities not resumed, 7 = Discharged - normal activities resumed

Description: Number of days taken for occurrence of each of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes/vassopressors) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73m^2), haemofiltration or dialysis

Description: The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: Diabetic ketoacidosis in patients on Ambrisentan & Dapagliflozin, New peripheral oedema in patients on Ambrisentan & Dapagliflozin arm

Description: The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days (chronically hypoxic individuals will be excluded from this analysis)

Description: The amount of time between a patient's first positive SARS-CoV2 PCR test and a patient's first negative SARS-CoV2 PCR test, measured in days

Description: The duration of oxygen therapy given to a patient, measured in days

Description: The duration of hospitalisation of a patient, measured in days

Description: The number of deaths recorded at 28 days irrespective of the cause

Description: The time to clinical improvement for a patient, defined as: >2 point improvement from Day 1 on the 7-point ordinal scale, measured in days

Primary Outcomes

Description: Titrated every second with automated oxygen titration device (FreeO2)

Description: Clinical improvement until hospital discharge

Secondary Outcomes

Description: Sepsis-related organ failure assessment (SOFA), national early warning score (NEWS2), early warning score for oxygen therapy (EWS.O2), decrease of at least 2 points on the 6-point ordinal scale

Primary Outcomes

Description: Change in composite COVID ordinal scale at day 15. Ordinal scale: 1) not hospitalized with resumption of normal activities; 2) not hospitalized, but unable to resume normal activities; 3) hospitalized, not requiring oxygen; 4) hospitalized, requiring oxygen; 5) hospitalized, requiring high-flow oxygen therapy, or noninvasive ventilation; 6) hospitalized, requiring invasive ventilation; 7) ventilation plus additional organ support such as pressors, renal replacement therapy and ECMO and 8) death. COVID Ordinal Scale ranges from 1 to 8, with score 1 on the scale corresponds to an ambulatory patient with minimal symptoms and score 8 on the scale corresponds to death.

Secondary Outcomes

Description: All-cause mortality assessed on day 15.

Description: All-cause mortality assessed on day 28.

Description: Supplemental Oxygen-free days

Description: Invasive-ventilator-free days

Description: ICU-free days

Description: Hospital-free days

Description: Decrease in the markers D-dimer/ Ferritin/ C-reactive protein

Description: Thromboembolic complications including stroke

Description: COVID ordinal scale

Primary Outcomes

Secondary Outcomes

Primary Outcomes

Description: number of days living without mechanical ventilation at D28

Primary Outcomes

Description: Primary outcome of the study is the number of patients alive without mechanical ventilation at day 15 after hospitalization.

Secondary Outcomes

Description: 0. Uninfected. Non viral RNA detected Ambulatory, Asymptomatic, viral RNA detected Ambulatory, Symptomatic, Independent Ambulatory, Symptomatic, Assistance needed Hospitalized, mild disease, No oxygen therapy needed Hospitalized, mild disease, Oxygen by mask of nasal prongs Hospitalized, severe disease, Oxygen by NIV or High flow Hospitalized, severe disease, Intubation and mechanical ventilation (pO2/FiO2>=150 OR SpO2/FIO2>=200) Hospitalized, severe disease, Mechanical ventilation (pO2/FiO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min) Hospitalized, severe disease, Mechanical ventilation pO2/FiO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO Death, Dead

Primary Outcomes

Description: Plasma viscosity will be measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.

Secondary Outcomes

Description: The number of participants dying from any cause will be compared between study arms.

Description: The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots.

Description: Time to treatment failure will be assessed in hours and is defined as plasma viscosity > 3.5 cP and/or the participant is a candidate for TPE as salvage therapy, as assessed by clinical team.

Description: The number of days spent in the ICU will be compared between study arms.

Description: The number of days spent in the hospital will be compared between study arms.

Description: The number of participants in each study arm discharged to home or to a long-term acute care hospital, versus palliative care or death.

Description: The clinical status of participants will be assessed with a single-item, 12-point ordinal scale. A score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death.

Description: Body temperature will be assessed in degrees Celsius.

Description: Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Description: Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Description: Heart rate will be assessed as beats per minute.

Description: Respiratory rate will be assessed as breaths per minute.

Description: The number of days participants are on a ventilator will be compared between study arms.

Description: The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.

Description: PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.

Description: Whether or not breathing assistance from vasopressors is needed will be compared between study arms.

Description: Whether or not breathing assistance from an RRT is needed will be compared between study arms.

Description: The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction.Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.

Description: The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).

Description: Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).

Description: The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.

Description: Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.

Description: A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%

Description: A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.

Description: MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).

Description: The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.

Description: The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.

Description: For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.

Description: The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.

Description: The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.

Description: A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.

Description: A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.

Description: Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.

Description: An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.

Description: The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.

Description: The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).

Description: Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.

Description: The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.

HP:0004377: Hematological neoplasm

Genes 351

Protein Mutations 0

SNP 0

HP:0001909: Leukemia

Genes 190

Protein Mutations 56

SNP 17

HP:0002664: Neoplasm

Genes 1515

Protein Mutations 75

SNP 8

HP:0002090: Pneumonia

Genes 220