BRAVO 临床研究方案：口服瓦瑞沙班抑制蛇毒中毒时的分泌型磷脂酶 A2。
The BRAVO Clinical Study Protocol: Oral Varespladib for Inhibition of Secretory Phospholipase A2 in the Treatment of Snakebite Envenoming.
机构信息
Ophirex, Inc., Corte Madera, CA 94295, USA.
Department of Emergency Medicine, Duke University, Durham, NC 27708, USA.
出版信息
Toxins (Basel). 2022 Dec 28;15(1):22. doi: 10.3390/toxins15010022.
INTRODUCTION
Snakebite is an urgent, unmet global medical need causing significant morbidity and mortality worldwide. Varespladib is a potent inhibitor of venom secretory phospholipase A (sPLA) that can be administered orally via its prodrug, varespladib-methyl. Extensive preclinical data support clinical evaluation of varespladib as a treatment for snakebite envenoming (SBE). The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies.
METHODS AND ANALYSIS
BRAVO (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care (SoC) vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned 1:1 to varespladib-methyl or placebo. The primary outcome is the Snakebite Severity Score (SSS) that has been modified for international use. This composite outcome is based on the sum of the pulmonary, cardiovascular, nervous, hematologic, and renal systems components of the updated SSS.
ETHICS AND DISSEMINATION
This protocol was submitted to regulatory authorities in India and the US. A Clinical Trial No Objection Certificate from the India Central Drugs Standard Control Organisation, Drug Controller General-India, and a Notice to Proceed from the US Food and Drug Administration have been obtained. The study protocol was approved by properly constituted, valid institutional review boards or ethics committees at each study site. This study is being conducted in compliance with the April 1996 ICH Guidance for Industry GCP E6, the Integrated Addendum to ICH E6 (R2) of November 2016, and the applicable regulations of the country in which the study is conducted. The trial is registered on Clinical trials.gov, NCT#04996264 and Clinical Trials Registry-India, 2021/07/045079 000062.
简介
蛇咬伤是一种紧急且未得到满足的全球性医疗需求，在全球范围内造成了大量的发病率和死亡率。Varespladib 是一种强效的毒液分泌型磷脂酶 A（sPLA）抑制剂，可通过其前药 varespladib-methyl 口服给药。广泛的临床前数据支持对 varespladib 作为蛇咬伤治疗药物（SBE）进行临床评估。本报告中介绍的方案旨在评估来自任何蛇种的多种地理位置的 varespladib-methyl 治疗 SBE 的效果。
方法与分析
BRAVO（广谱快速解毒剂：varespladib 口服治疗蛇咬伤）是一项多中心、随机、双盲、安慰剂对照、2 期研究，旨在评估口服 varespladib-methyl 联合标准治疗（SoC）与 SoC 联合安慰剂治疗任何毒蛇咬伤的患者的安全性、耐受性和疗效。符合入选标准的 5 岁及以上男性和女性患者将按 1:1 随机分配至 varespladib-methyl 组或安慰剂组。主要结局是为国际使用而修改的蛇咬伤严重程度评分（SSS）。该综合结局基于更新后的 SSS 的肺、心血管、神经、血液和肾脏系统成分的总和。
伦理与传播
本方案已提交给印度和美国的监管机构。印度中央药品标准控制组织、印度药品管制总局的临床研究无异议证书和美国食品和药物管理局的开展通知已获得。该研究方案已获得每个研究地点的适当组成、有效的机构审查委员会或伦理委员会的批准。该研究符合 1996 年 4 月 ICH 行业 GCP E6 指南、2016 年 11 月 ICH E6（R2）综合附录以及研究开展国家的适用法规。该试验在 ClinicalTrials.gov 注册，NCT#04996264 和 Clinical Trials Registry-India，2021/07/045079 000062。
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