普罗芦卡胺（GT0918）治疗 COVID-19 重症或危重症患者的疗效和安全性：一项前瞻性、开放标签、单臂、单中心探索性试验的研究方案。

Efficacy and safety of proxalutamide (GT0918) in severe or critically ill patients with COVID-19: study protocol for a prospective, open-label, single-arm, single-center exploratory trial.

机构信息

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai, China.

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.

出版信息

BMC Pharmacol Toxicol. 2023 Jun 15;24(1):38. doi: 10.1186/s40360-023-00678-7.

DOI:10.1186/s40360-023-00678-7

PMID:37322522

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10268455/

Abstract

BACKGROUND

The rapid worldwide spread of COVID-19 has caused a global health challenge with high mortality of severe or critically ill patients with COVID-19. To date, there is no specific efficient therapeutics for severe or critically ill patients with COVID-19. It has been reported that androgen is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Proxalutamide as an androgen receptor antagonist has shown potential treatment effects on COVID-19 patients. Thus, this trial is designed to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19.

METHODS

This single-arm, open-label, single-center prospective exploratory trial is planned to recruit 64 severe or critically ill patients with COVID-19 in China. Recruitment started on 16 May 2022 and is foreseen to end on 16 May 2023. Patients will be followed-up until 60 days or death, whichever comes first. The primary outcome is the 30-day all-cause mortality. Secondary endpoints included 60-day all-cause mortality, rate of clinical deterioration within 30 days after administration, time to sustain clinical recovery (determined using an 8-point ordinal scale), mean change in the Acute Physiology and Chronic Health Evaluation II scores, change in oxygenation index, changes in chest CT scan, percentage of patients confirmed negative for SARS-CoV-2 by nasopharyngeal swab, change in Ct values of SARS-CoV-2 and safety. Visits will be performed on days 1 (baseline), 15 or 30, 22, and 60.

DISCUSSION

The trial is the first to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. The findings of this study might lead to the development of better treatment for COVID-19 and provide convincing evidence regarding the efficacy and safety of proxalutamide.

TRIAL REGISTRATION

This study was registered on 18 June 2022 at the Chinese Clinical Trial Registry (ChiCTR2200061250).

摘要

背景

COVID-19 在全球范围内迅速传播，给全球带来了严峻的健康挑战，导致大量重症或危重症 COVID-19 患者死亡。迄今为止，针对重症或危重症 COVID-19 患者尚无特效疗法。有报道称雄激素与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染有关。作为雄激素受体拮抗剂的普罗芦胺在 COVID-19 患者中显示出了一定的治疗效果。因此，本试验旨在研究普罗芦胺治疗 COVID-19 重症或危重症患者的疗效和安全性。

方法

这是一项单臂、开放标签、单中心前瞻性探索性试验，计划在中国招募 64 例 COVID-19 重症或危重症患者。招募工作于 2022 年 5 月 16 日开始，预计于 2023 年 5 月 16 日结束。患者将随访至 60 天或死亡，以先发生者为准。主要结局指标为 30 天全因死亡率。次要结局指标包括 60 天全因死亡率、治疗后 30 天内临床恶化率、临床恢复持续时间（采用 8 分序贯量表确定）、急性生理学与慢性健康状况评分系统Ⅱ评分的平均变化、氧合指数变化、胸部 CT 扫描变化、鼻咽拭子 SARS-CoV-2 检测转阴患者百分比、SARS-CoV-2 的 Ct 值变化和安全性。访视时间点为第 1 天（基线）、第 15 天或第 30 天、第 22 天和第 60 天。