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有效警示还是临床传闻:多中心匹配队列中肾功能损害患者使用瑞德西韦的安全性结局评估。

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort.

机构信息

Department of Pharmacy, Yale New Haven Health System, New Haven, Connecticut, USA.

Yale University School of Medicine, Department of Internal Medicine, Section of Infectious Diseases, New Haven, Connecticut, USA.

出版信息

Antimicrob Agents Chemother. 2021 Jan 20;65(2). doi: 10.1128/AAC.02290-20.

Abstract

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of <30 ml/min and an eCrCl of ≥30 ml/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl of <30 ml/min were older {median, 80 years (interquartile range [IQR], 63.8 to 89) versus 62 (IQR, 54 to 74);  < 0.001}, were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%;  = 0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%;  = 0.01) than those with an eCrCl of ≥30 ml/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%;  = 0.283) or early discontinuation due to abnormal liver function tests (LFTs) (0% versus 3.9%;  = 0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30 ml/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. In conclusion, remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl of <30 ml/min compared to patients with an eCrCl of ≥30 ml/min.

摘要

根据规定,鉴于缺乏该患者人群的安全性数据,不建议将瑞德西韦用于有肾脏疾病的 SARS-CoV-2 患者。本研究为一项多中心、回顾性病历研究,纳入了接受瑞德西韦治疗的住院 SARS-CoV-2 患者。比较了估计肌酐清除率(eCrCl)<30ml/min 和 eCrCl≥30ml/min 的患者之间的安全性结局。主要终点是治疗结束时(EOT)的急性肾损伤(AKI)。在接受瑞德西韦治疗的 359 名患者中,347 名符合纳入标准。eCrCl<30ml/min 的患者年龄较大{中位数 80 岁(四分位距[IQR] 63.8 至 89)比 62 岁(IQR 54 至 74); <0.001},在接受瑞德西韦治疗当天更有可能使用血管加压药(30%比 12.7%;  = 0.003),并且在接受瑞德西韦治疗期间更有可能需要机械通气(27.5%比 12.4%;  = 0.01)。尽管存在这些混杂因素,但 eCrCl≥30ml/min 患者 EOT AKI 发生率(5%比 2.3%;  = 0.283)或因异常肝功能检查(LFTs)而早期停药(0%比 3.9%;  = 0.374)并无显著差异。在 eCrCl<30ml/min 的接受瑞德西韦治疗的患者中,有 5%的患者在 EOT 时发生 AKI,但根据治疗医生的评估,没有一例归因于瑞德西韦治疗。应用 1:1 最近邻匹配来校正基线混杂因素后,观察到了类似的安全性结局。结论:与 eCrCl≥30ml/min 的患者相比,eCrCl<30ml/min 的患者接受瑞德西韦治疗与 EOT AKI 发生率增加无关。

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