Prospective Study of Treatment with Ensitrelvir for COVID-19 in Patients Undergoing Hemodialysis (PROTECT-HD).

IF 5.3 3区医学 Q1 INFECTIOUS DISEASES

Infectious Diseases and Therapy Pub Date : 2026-05-01 Epub Date: 2026-04-01 DOI:10.1007/s40121-026-01327-2

Mineaki Kitamura, Takahiro Takazono, Naoki Hosogaya, Shimpei Morimoto, Masahiro Kinoshita, Eriko Hamada, Ryosuke Shimizu, Shogo Miyazawa, Shintaro Tanaka, Tomoya Nishino, Hiroshi Mukae

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引用次数: 0

Abstract

Introduction: Patients on hemodialysis (HD) are vulnerable to COVID-19 and often excluded from pivotal antiviral trials. Ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor approved in Japan, remains unevaluated in patients undergoing HD. This study assesses the pharmacokinetics, antiviral activity, safety, and clinical effectiveness of ensitrelvir in participants with mild COVID-19 undergoing HD.

Methods: In this prospective, single-arm, open-label study (December 2024-April 2025), participants with mild COVID-19 undergoing HD received ensitrelvir 375 mg on Day 1, followed by 125 mg once daily on Days 2-5. On Visit 2 (Day 3), plasma ensitrelvir concentrations were measured at three time points prior to ensitrelvir administration-before, during, and after dialysis. On Visit 3 (Day 5), blood samples were collected after dialysis and prior to ensitrelvir administration. Clinical outcomes, body temperature, SARS-CoV-2 viral load, and viral titers were monitored through Day 8. The primary endpoint was plasma concentration of ensitrelvir relative to dialysis; secondary endpoints included clinical outcomes, body temperature, and changes in viral load.

Results: Eight participants were evaluated: mean age, 68.1 years; mean body weight, 58.0 kg; and mean body mass index, 24.1 kg/m². Plasma ensitrelvir concentrations (geometric mean) remained stable, with similar levels before (18.0 µg/mL) and after dialysis (16.4 µg/mL). All participants were judged clinically effective by the investigator by Day 8. Body temperature normalized within 16.6-48.0 h in four participants, and in one participant after 59.2 h. SARS-CoV-2 viral load (mean ± standard deviation) declined by 2.85 ± 1.52 log₁₀ copies/mL from baseline to Day 8. No treatment-emergent adverse events, hospitalizations, or severe COVID-19-related complications occurred.

Conclusion: No dose adjustment was required regardless of HD. In participants with mild COVID-19 undergoing HD, plasma ensitrelvir concentrations were similar to those previously reported in healthy individuals. Ensitrelvir showed favorable antiviral and clinical responses, supporting its safe use without dose adjustments.

Trial registration: Japan Registry of Clinical Trials ID: jRCTs071240069.

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Ensitrelvir治疗血液透析患者COVID-19 （PROTECT-HD）的前瞻性研究

血液透析（HD）患者易感染COVID-19，通常被排除在关键抗病毒试验之外。Ensitrelvir是一种口服sars - cov - 23c样蛋白酶抑制剂，已在日本获得批准，但仍未对HD患者进行评估。本研究评估了ensitrelvir在患有轻度COVID-19的HD患者中的药代动力学、抗病毒活性、安全性和临床有效性。方法：在这项前瞻性、单组、开放标签研究（2024年12月- 2025年4月）中，患有轻度COVID-19的HD患者在第1天接受ensitrelvir 375 mg，随后在第2-5天每天一次125 mg。在第2次访问（第3天），在给予恩司替韦之前的三个时间点（透析前、透析中和透析后）测量血浆恩司替韦浓度。第3次访问（第5天），在透析后和给予恩司他韦之前采集血液样本。在第8天监测临床结果、体温、SARS-CoV-2病毒载量和病毒滴度。主要终点是相对于透析的血浆ensitrelvir浓度；次要终点包括临床结果、体温和病毒载量的变化。结果：共纳入8例受试者，平均年龄68.1岁；平均体重58.0 kg；平均体重指数为24.1 kg/m2。血浆ensitrelvir浓度（几何平均值）保持稳定，透析前（18.0µg/mL）和透析后（16.4µg/mL）的水平相似。所有参与者在第8天被研究者判定为临床有效。4名参与者的体温在16.6-48.0小时内恢复正常，1名参与者的体温在59.2小时后恢复正常。从基线到第8天，SARS-CoV-2病毒载量（平均值±标准差）下降了2.85±1.52 log10拷贝/mL。未发生治疗后出现的不良事件、住院或与covid -19相关的严重并发症。结论：与HD无关，不需要调整剂量。在患有轻度COVID-19的HD患者中，血浆ensitrelvir浓度与先前报道的健康个体相似。Ensitrelvir显示出良好的抗病毒和临床反应，支持其无需剂量调整的安全使用。试验注册：日本临床试验注册中心ID: jRCTs071240069。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infectious Diseases and Therapy Medicine-Microbiology (medical)

CiteScore

8.60

自引率

1.90%

发文量

136

审稿时长

6 weeks

期刊介绍： Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.