| 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. |
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