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)

COVID-19 Clinical Trial

— REDPINE  

Official title:

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Remdesivir in Participants With Severely Reduced Kidney Function Who Are Hospitalized for COVID-19

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04745351
• Other study ID #: GS-US-540-5912
• Secondary ID: 2020-005416-22DO
• Status: Terminated
• Phase: Phase 3
• Start date: March 31, 2021
• Est. completion date: May 24, 2022

Study information

• Verified date: April 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 249
• Est. completion date: May 24, 2022
• Est. primary completion date: April 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Remdesivir
Administered as Intravenous (IV) infusion once daily
• RDV Placebo
Administered as IV saline once daily
• Standard of Care
Standard of Care Treatment for COVID-19 Infection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Brazil,  Portugal,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With All-cause Death or Invasive Mechanical Ventilation (IMV) Through 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.	First dose date up to Day 29
Secondary	All-cause Mortality Through Day 29	The reported percentage was from the Kaplan-Meier estimate.	First dose date up to Day 29
Secondary	Percentage of Participants With Initiation of IMV Through Day 29	The reported percentage was the cumulative-incidence estimate.	First dose date up to Day 29
Secondary	Time to Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) by 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.	First dose date up to Day 29
Secondary	Time to Recovery Independent of Further Worsening by 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.	First dose date up to Day 29
Secondary	Percentage of Participants Within Each Clinical Status Category as Assessed by an 8-Point Ordinal Scale on 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.	Day 15
Secondary	Percentage of Participants Within Each Clinical Status Category as Assessed by an 8-Point Ordinal Scale on 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.	Day 29
Secondary	Renal Replacement Therapy (RRT)-Free Days (Among Those Without End-Stage Kidney Disease [ESKD] at Baseline) Through 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.	First dose date up to Day 29
Secondary	Percentage of Participants With Recovery Without Subsequent Worsening (Defined as an Ordinal Scale Score of > 4) Through 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.	First dose date up to Day 29
Secondary	Percentage of Participants With Recovery Independent of Further Worsening Through 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.	First dose date up to Day 29
Secondary	Percentage of Participants Experiencing Serious Adverse Events (SAEs)	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.	First dose date up to last dose date (Maximum: 5 days) plus 30 days
Secondary	Percentage of Participants Who Permanently Discontinued Investigational Drug Due to Adverse Events (AEs)	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.	First dose date up to last dose date (Maximum: 5 days)

External Links

•   Gilead Clinical Trials Website