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)
Holy Cross Hospital
🇺🇸Silver Spring, Maryland, United States
MedStar Health Research Institute
🇺🇸Washington, District of Columbia, United States
George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Complejo Asistencial Universitario de Salamanca - H. Clinico
🇪🇸Salamanca, Spain
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Hospital Nélio Mendonça,
🇵🇹Funchal, Portugal
St. Joseph Hospital Eureka
🇺🇸Eureka, California, United States
Northwestern Medicine Central DuPage Hospital
🇺🇸Winfield, Illinois, United States
Hospital General Universitario de Elche
🇪🇸Elche, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Barts Health NHS Trust, The Royal London Hospital
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Centro Hospitalar de Vila Nova de Gaia
🇵🇹Vila Nova de Gaia, Portugal
Kings College Hospital
🇬🇧London, United Kingdom
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
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
Hoag Memorial Hospital Presbyterian, 16200 Sand Canyon Ave
🇺🇸Irvine, California, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Holy Cross Hospital, 19801 Observation Dr
🇺🇸Germantown, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Newton-Wellesley Hospital
🇺🇸Newton, Massachusetts, United States
St. Clair Nephrology Research
🇺🇸Grosse Pointe Woods, Michigan, United States
G.V. (Sonny) Montgomery VAMC
🇺🇸Jackson, Michigan, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
New York - Presbyterian Hospital/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
PMG Infectious Disease Consultants (administrative)
🇺🇸Portland, Oregon, United States
Memorial Hermann Hospital at TMC
🇺🇸Houston, Texas, United States
Providence Regional Medical Center Everett
🇺🇸Everett, Washington, United States
Providence Health Care
🇺🇸Spokane, Washington, United States
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
🇧🇷São José do Rio Preto, Brazil
Providence Health Care, 5633 N Lidgerwood
🇺🇸Spokane, Washington, United States
MultiCare Good Samaritan Hospital
🇺🇸Tacoma, Washington, United States
Hospital e Maternidade Celso Pierro/ Sociedade Campineira de Educacao e Instrucao/ PUC Campinas
🇧🇷Campinas, Brazil
Centro Hospitalar Cova da Beira EPE
🇵🇹Covilhã, Portugal
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, Brazil
Centro Hospitalar Lisboa Ocidental
🇵🇹Lisbon, Portugal
Centro Hospitalar do Porto - Hospital de Santo Antonio
🇵🇹Odivelas, Portugal
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Germans Trias I Pujol
🇪🇸Badalona, Spain
George Regional Hospital
🇿🇦George, South Africa
Mediclinic Vergelegen
🇿🇦Somerset West, South Africa
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Nossa Senhora das Gracas
🇧🇷Curitiba, Brazil
North Florida/ South Georgia Veterans Health System
🇺🇸Gainesville, Florida, United States
Mayo Clinic Hospital
🇺🇸Rochester, Minnesota, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
Genesis Clinical Research
🇺🇸Tampa, Florida, United States
Tulane Medical Center, 2000 Canal St.
🇺🇸New Orleans, Louisiana, United States
Wake Forest University Health Sciences
🇺🇸Bethesda, Maryland, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
VCU Health Medical Center
🇺🇸Richmond, Virginia, United States