在因 COVID-19 肺炎住院的肾功能受损人群中使用瑞德西韦的疗效和安全性：一项随机临床试验。
Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial.
机构信息
Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Fight Infections Foundation, Service of Infectious Diseases, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
出版信息
Clin Infect Dis. 2024 Nov 22;79(5):1172-1181. doi: 10.1093/cid/ciae333.
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.
背景
针对患有 2019 年冠状病毒病（COVID-19）和肾脏损伤的患者，目前研究的抗病毒疗法寥寥无几。在此，我们评估了瑞德西韦及其代谢物以及磺丁基醚-β-环糊精赋形剂在住院 COVID-19 合并严重肾脏损伤患者中的疗效、安全性和药代动力学。
方法
在 REDPINE 这项 3 期、随机、双盲、安慰剂对照研究中，年龄≥12 岁的因 COVID-19 肺炎合并急性肾损伤、慢性肾脏病或肾衰竭而住院的患者，按 2:1 的比例随机分组，接受静脉注射瑞德西韦（第 1 天 200mg；第 1-5 天每天 100mg）或安慰剂（招募时间为 2021 年 3 月至 2022 年 3 月）。主要疗效终点是第 29 天全因死亡率或有创机械通气率的复合终点。安全性评估至第 60 天。
结果
尽管提前结束了入组，但仍有 243 名患者入组并接受了治疗（瑞德西韦组 n=163；安慰剂组 n=80）。基线时，90 名患者（37.0%）存在急性肾损伤（瑞德西韦组 n=60；安慰剂组 n=30），64 名患者（26.3%）存在慢性肾脏病（瑞德西韦组 n=44；安慰剂组 n=20），89 名患者（36.6%）存在肾衰竭（瑞德西韦组 n=59；安慰剂组 n=30）；31 名患者（12.8%）接种过 COVID-19 疫苗。瑞德西韦组和安慰剂组第 29 天的全因死亡率或有创机械通气率分别为 29.4%和 32.5%（P=0.61）。瑞德西韦组和安慰剂组分别有 80.4%和 77.5%的患者出现治疗出现的不良事件，分别有 50.3%和 50.0%的患者出现严重不良事件。
结论
尽管本研究的效力不足，但治疗组之间未观察到疗效有显著差异。REDPINE 表明瑞德西韦在 COVID-19 合并严重肾脏损伤的患者中是安全的。
临床试验注册
EudraCT 2020-005416-22；ClinicalTrials.gov NCT04745351。
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