Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial

Abstract

Background: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment.

Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60.

Results: Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function.

Conclusions: Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment.

Clinical trials registration: EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351.

Keywords: COVID-19; SARS-CoV-2; kidney impairment; remdesivir.

Figure 1.

Participant disposition. If participants did not meet all eligibility criteria, they were not randomized; the individual reasons for ineligibility were not captured. Two participants met all eligibility criteria and were not randomized at the investigator's discretion. The number of participants who completed the study corresponded to the number randomized and treated, excluding those who prematurely discontinued the study.

Figure 2.

Kaplan-Meier estimate of time to all-cause death or invasive mechanical ventilation (IMV). The number at risk represents the number of participants remaining at risk at the beginning of the interval. Participants who did not begin to receive IMV or die by day 29 were censored on their last study day or day 29, whichever was earlier. Abbreviations: AKI, acute kidney injury; CI, confidence interval; CKD, chronic kidney disease; HR, hazard ratio.

Figure 3.

Median (interquartile range) serum creatinine change in participants with (A) acute kidney injury (AKI) or (B) chronic kidney disease (CKD). Reference line represents no change from baseline (ie, y = 0). Kidney disease status categories are mutually exclusive; for participants without dialysis-treated chronic kidney failure at screening, the status was AKI in participants with ongoing AKI and CKD in those with a history of CKD.