REDPINE: 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)

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT04745351

Collaborator

(none)

249

Enrollment

Locations

Arms

13.8

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Remdesivir Drug: RDV Placebo Drug: Standard of Care	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

249 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 31, 2021

Actual Primary Completion Date :

Apr 20, 2022

Actual Study Completion Date :

May 24, 2022

Arms and Interventions

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: GS-5734™ Veklury® Drug: Standard of Care Standard of Care Treatment for COVID-19 Infection
Placebo Comparator: Placebo Participants will receive continued SOC therapy together with RDV placebo on Day 1 followed by RDV placebo from Day 2 up to Day 5.	Drug: RDV Placebo Administered as IV saline once daily Drug: Standard of Care Standard of Care Treatment for COVID-19 Infection

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:

GS-5734™

Veklury®

Drug: Standard of Care

Standard of Care Treatment for COVID-19 Infection

Placebo Comparator: Placebo

Participants will receive continued SOC therapy together with RDV placebo on Day 1 followed by RDV placebo from Day 2 up to Day 5.

Drug: RDV Placebo

Administered as IV saline once daily

Drug: Standard of Care

Standard of Care Treatment for COVID-19 Infection

Outcome Measures

Primary Outcome Measures

Composite of All-Cause Mortality or Invasive Mechanical Ventilation (IMV) Through Day 29 [First dose date up to Day 29]
The composite of all-cause mortality or IMV is the combined endpoint of the percentage of participants who die or initiate on IMV through Day 29.

Secondary Outcome Measures

All-Cause Mortality Through Day 29 [First dose date up to Day 29]
The percentage of participants who die through Day 29 will be assessed.
Invasive Mechanical Ventilation Through Day 29 [First dose date up to Day 29]
The percentage of participants who initiate on IMV through Day 29 will be assessed.
Time to Recovery [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 satisfies one of the following three categories from the 8-point ordinal scale: 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).
Clinical Status 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 will be recorded. The 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 invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8. Death. Higher scores indicate worst clinical status.
Clinical Status 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 will be recorded. The 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 invasive mechanical ventilation or ECMO; and 8. Death. Higher scores indicate worst clinical status.
Renal Replacement Therapy (RRT)-Free Days (Among Those Without End-Stage Kidney Disease [ESKD] at Randomization) Through Day 29 [First dose date up to Day 29]
Recovery Through Day 29 [First dose date up to Day 29]
Recovery is defined as the participant satisfying one of the following three categories from the 8-point ordinal scale: 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).
Percentage of Participants Experiencing Serious Adverse Events (SAEs) [First dose date up to last dose date (Maximum: Day 5) plus 30 days]
Percentage of Participants who Permanently Discontinue Investigational Drug due to Adverse Events (AEs) [First dose date up to last dose date (Maximum: Day 5) plus 30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:
1. 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
1. 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, ECMO, or 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Gilead Clinical Trials Website

Publications

None provided.

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT04745351

Other Study ID Numbers:

GS-US-540-5912
2020-005416-22
DOH-27-012022-4779

First Posted:

Feb 9, 2021

Last Update Posted:

Jun 3, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

COVID-19

Remdesivir

Study Results

No Results Posted as of Jun 3, 2022