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) (REDPINE)

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

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).

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Remdesivir; Drug: Standard of Care; Drug: RDV Placebo

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Brazil
  • Campinas, Brazil, 13060-904
    • Hospital e Maternidade Celso Pierro/ Sociedade Campineira de Educacao e Instrucao/ PUC Campinas
  • Curitiba, Brazil, 80810-040
    • Hospital Nossa Senhora das Graças
  • Sao Paulo, Brazil, 01323-020
    • Hospital Alemao Oswaldo Cruz
  • São José do Rio Preto, Brazil, 15090-000
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
• Portugal
  • Covilhã, Portugal, 6200-251
    • Centro Hospitalar Cova da Beira EPE
  • Funchal, Portugal, 9000-514
    • Hospital Nélio Mendonça,
  • Lisbon, Portugal, 1449-005
    • Centro Hospitalar Lisboa Ocidental
  • Odivelas, Portugal, 2620-144
    • Centro Hospitalar do Porto - Hospital de Santo António
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia
• South Africa
  • George, South Africa, 6529
    • George Regional Hospital
  • Somerset West, South Africa, 7130
    • Mediclinic Vergelegen
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitario Germans Trias i Pujol
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Elche, Spain, 3203
    • Hospital General Universitario de Elche
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca - H. Clinico
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust, The Royal London Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Hospital
    • Birmingham, Alabama, United States, 35205
      • St. Vincent's Health System
    • Mobile, Alabama, United States, 36608
      • Pulmonary Associates of Mobile, P.C.
  • California
    • Eureka, California, United States, 95501
      • St. Joseph Hospital Eureka
    • Irvine, California, United States, 92618
      • Hoag Memorial Hospital Presbyterian, 16200 Sand Canyon Ave
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Torrance, California, United States, 90505
      • Torrance Memorial Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Health Research Institute
    • Washington, District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates
  • Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/ South Georgia Veterans Health System
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research
  • Illinois
    • Winfield, Illinois, United States, 60190
      • Northwestern Medicine Central DuPage Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center, 2000 Canal St.
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Wake Forest University Health Sciences
    • Germantown, Maryland, United States, 20876
      • Holy Cross Hospital, 19801 Observation Dr
    • Silver Spring, Maryland, United States, 20910
      • Holy Cross Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Newton, Massachusetts, United States, 02462
      • Newton-Wellesley Hospital
  • Michigan
    • Grosse Pointe Woods, Michigan, United States, 48236
      • St. Clair Nephrology Research
    • Jackson, Michigan, United States, 39216
      • G.V. (Sonny) Montgomery VAMC
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Hospital
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Hospital
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • New York, New York, United States, 10065
      • New York - Presbyterian Hospital/Weill Cornell Medical Center
    • Stony Brook, New York, United States, 11716
      • Stony Brook University Hospital
  • Oregon
    • Portland, Oregon, United States, 92775
      • PMG Infectious Disease Consultants (administrative)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 92037
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital at TMC
  • Virginia
    • Richmond, Virginia, United States, 23298
      • VCU Health Medical Center
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
    • Spokane, Washington, United States, 99204
      • Providence Health Care
    • Spokane, Washington, United States, 99208
      • Providence Health Care, 5633 N Lidgerwood
    • Tacoma, Washington, United States, 98405
      • MultiCare Good Samaritan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remdesivir (RDV); 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.	Drug: Remdesivir; Administered as Intravenous (IV) infusion once daily; Other Names: Veklury®; GS-5734™; Drug: Standard of Care; Standard of Care Treatment for COVID-19 Infection
Placebo Comparator: 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.	Drug: Standard of Care; Standard of Care Treatment for COVID-19 Infection; Drug: RDV Placebo; Administered as IV saline once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality Through Day 29	The reported percentage was from the Kaplan-Meier estimate.	First dose date up to Day 29
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
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
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
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
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
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
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
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
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
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)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): April 20, 2022
• Study Completion (Actual): May 24, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: GS-US-540-5912; 2020-005416-22 (EudraCT Number); DOH-27-012022-4779 (Registry Identifier: South African Clinical Trials Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No