Study to Evaluate the Efficacy and Safety of Remdesivir in Participants With Severely Reduced Kidney Function Who Are Hospitalized for Coronavirus Disease 2019 (COVID-19)
- Conditions
- COVID-19
- Interventions
- Registration Number
- NCT04745351
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate whether remdesivir (RDV, GS-5734™) reduces the composite risk of death or invasive mechanical ventilation (IMV) through Day 29 in participants with severely reduced kidney function who are hospitalized for coronavirus disease 2019 (COVID-19).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 249
-
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive as determined by Polymerase Chain Reaction (PCR) or other commercially available or public health assay (eg, Nucleic Acid Amplification Test (NAAT) and antigen tests) in any respiratory specimen
-
Hospitalized for COVID-19
-
Weighing at least 40 kilograms (kg)
-
Oxygen (O2) saturation ≤ 94% on room air or requiring O2 supplement or Radiographic evidence of pulmonary infiltrates for COVID-19
-
Have either:
- a) Severely reduced kidney function (estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m^2), including people with end-stage kidney disease (ESKD) requiring chronic dialysis
- b) Ongoing acute kidney injury (AKI): defined as a 50% increase in serum creatinine (SCr) within a 48-hour period that is sustained (ie, requires confirmatory SCr) for ≥ 6 hours despite supportive care
-
The interval between COVID-19 symptoms onset and randomization is no more than 10 days
Key
- Received any investigational drug, RDV, or other antiviral treatment for COVID-19
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal
- Invasive mechanical ventilation, noninvasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO), or renal replacement therapy (RRT) for acute kidney injury (AKI)
- Positive serum pregnancy test at screening for women of childbearing potential or currently breastfeeding
- Known hypersensitivity to the study drug, metabolites, or formulation sulfobutylether-beta-cyclodextrin (SBECD)
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Remdesivir (RDV) Standard of Care Participants will receive continued Standard of Care (SOC) therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg from Day 2 up to Day 5. Placebo RDV Placebo Participants will receive continued SOC therapy together with RDV matching placebo on Day 1 followed by RDV matching placebo from Day 2 up to Day 5. Placebo Standard of Care Participants will receive continued SOC therapy together with RDV matching placebo on Day 1 followed by RDV matching placebo from Day 2 up to Day 5. Remdesivir (RDV) Remdesivir Participants will receive continued Standard of Care (SOC) therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg from Day 2 up to Day 5.
- Primary Outcome Measures
Name Time Method Percentage of Participants With All-cause Death or Invasive Mechanical Ventilation (IMV) Through Day 29 First dose date up to Day 29 This is the combined outcome measure reporting the percentage of participants with all-cause death or IMV through Day 29. The reported percentage was from the Kaplan-Meier estimate.
- Secondary Outcome Measures
Name Time Method Renal Replacement Therapy (RRT)-Free Days (Among Those Without End-Stage Kidney Disease [ESKD] at Baseline) Through Day 29 First dose date up to Day 29 The number of RRT free days were calculated as the number of full days from Day 1 to Day 29 on which the participant was alive and did not receive RRT.
Percentage of Participants With Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) Through Day 29 First dose date up to Day 29 Recovery is defined as the first day on which the participant with a baseline score \>= 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale including: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on IMV or ECMO; 8) Death.
Percentage of Participants With Recovery Independent of Further Worsening Through Day 29 First dose date up to Day 29 Recovery is defined as the first day on which the participant with a baseline score \>= 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale including: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on IMV or ECMO; 8) Death.
Percentage of Participants Experiencing Serious Adverse Events (SAEs) First dose date up to last dose date (Maximum: 5 days) plus 30 days An SAE was defined as an event that, at any dose, results in the following: Death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, a medically important event or reaction which may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other outcomes constituting SAEs.
Percentage of Participants Who Permanently Discontinued Investigational Drug Due to Adverse Events (AEs) First dose date up to last dose date (Maximum: 5 days) An AE is any untoward medical occurrence in a clinical study participant administered an investigational drug, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of an investigational drug, whether or not the AE is considered related to the investigational drug.
Time to Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) by Day 29 First dose date up to Day 29 Time to recovery is the time from first dose to recovery. Recovery is defined as the first day on which the participant with a baseline score ≥ 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. Cumulative incidence was reported.
Time to Recovery Independent of Further Worsening by Day 29 First dose date up to Day 29 Time to recovery is the time from first dose to recovery. Recovery is defined as the first day on which the participant with a baseline score ≥ 4, satisfies categories 1, 2, or 3 from the 8-point ordinal scale: 1) Non-hospitalized, no limitations on activities; 2) Non-hospitalized, limitations on activities/requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19; 5) Hospitalized, supplemental oxygen; 6) Hospitalized, on noninvasive ventilation; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. Cumulative incidence was reported.
All-cause Mortality Through Day 29 First dose date up to Day 29 The reported percentage was from the Kaplan-Meier estimate.
Percentage of Participants Within Each Clinical Status Category as Assessed by an 8-Point Ordinal Scale on Day 15 Day 15 Clinical status is derived from death, hospital discharge, and the ordinal scale. Each day, the worst (highest) score from the previous day was recorded. The 8-point Ordinal scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per-protocol RDV/saline as placebo administration); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19-specific medical care (other than per-protocol RDV administration); 5. Hospitalized, supplemental oxygen; 6. Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on IMV or ECMO; and 8. Death. Higher scores indicate worse clinical status.
Percentage of Participants Within Each Clinical Status Category as Assessed by an 8-Point Ordinal Scale on Day 29 Day 29 Clinical status is derived from death, hospital discharge, and the ordinal scale. Each day, the worst (highest) score from the previous day was recorded. The 8-point Ordinal scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per-protocol RDV/saline as placebo administration); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care for COVID-19-specific medical care (other than per-protocol RDV administration); 5. Hospitalized, supplemental oxygen; 6. Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on IMV or ECMO; and 8. Death. Higher scores indicate worse clinical status.
Percentage of Participants With Initiation of IMV Through Day 29 First dose date up to Day 29 The reported percentage was the cumulative-incidence estimate.
Trial Locations
- Locations (63)
St. Vincent's Health System
🇺🇸Birmingham, Alabama, United States
UAB Hospital
🇺🇸Birmingham, Alabama, United States
Pulmonary Associates of Mobile, P.C.
🇺🇸Mobile, Alabama, United States
St. Joseph Hospital Eureka
🇺🇸Eureka, California, United States
Hoag Memorial Hospital Presbyterian, 16200 Sand Canyon Ave
🇺🇸Irvine, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
MedStar Health Research Institute
🇺🇸Washington, District of Columbia, United States
George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Scroll for more (53 remaining)St. Vincent's Health System🇺🇸Birmingham, Alabama, United States