Duke University School of Medicine, Durham, North Carolina, USA.
Ophirex, Inc, Corte Madera, California, USA.
BMJ Glob Health. 2024 Oct 22;9(10):e015985. doi: 10.1136/bmjgh-2024-015985.
Snakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component of snake venoms. We conducted a phase II clinical trial to assess efficacy and safety of oral varespladib methyl in patients bitten by venomous snakes.
This double-blind, randomised, placebo-controlled trial enrolled patients in emergency departments in India and the USA. Patients with SBE were randomly assigned (1:1) to receive varespladib methyl or placebo two times per day for 1 week. All patients received standard of care, including antivenom. The primary outcome was change in the composite Snakebite Severity Score (SSS) measuring the severity of envenoming, from baseline to the average composite SSS at 6 and 9 hours.
Among 95 patients randomised August 2021 through November 2022, the most common snakebites were from Russell's vipers (n=29), copperheads (n=18) and rattlesnakes (n=14). The SSS improved from baseline to the average at 6 and 9 hours by 1.1 (95% CI, 0.7 to 1.6) in the varespladib group versus 1.5 (95% CI, 1.0 to 2.0) in the placebo group (difference -0.4, 95% CI, -0.8 to 0.1, p=0.13). While key secondary outcomes were not statistically different by treatment group, benefit was seen in the prespecified subgroup initiating study drug within 5 hours of bite (n=37). For this early treatment group, clinically important differences were observed for illness severity over the first week, patient-reported function on days 3 and 7 and complete recovery. No death or treatment emergent serious adverse event occurred.
For emergency department treatment of snakebites, the addition of varespladib to antivenom did not find evidence of difference for the primary outcome based on the SSS. A potentially promising signal of benefit was observed in patients initiating treatment within 5 hours of snakebite.
蛇伤（SBE）每年导致超过 50 万人死亡或致残。瓦瑞沙帕丁甲基，一种口服分泌型磷脂酶 A2 抑制剂，是蛇毒中几乎无处不在的成分。我们进行了一项 II 期临床试验，以评估口服瓦瑞沙帕丁甲基在被毒蛇咬伤的患者中的疗效和安全性。
这项双盲、随机、安慰剂对照试验在印度和美国的急诊室招募了患者。SBE 患者被随机（1:1）分为瓦瑞沙帕丁甲基组或安慰剂组，每天两次，疗程为 1 周。所有患者均接受标准治疗，包括抗蛇毒血清。主要结局是从基线到 6 小时和 9 小时的平均复合蛇伤严重程度评分（SSS）测量的蛇伤严重程度的变化。
在 2021 年 8 月至 2022 年 11 月期间随机分配的 95 名患者中，最常见的蛇咬伤来自罗素的毒蛇（n=29）、铜头蛇（n=18）和响尾蛇（n=14）。与安慰剂组相比，瓦瑞沙帕丁组从基线到 6 小时和 9 小时的 SSS 平均改善了 1.1（95%CI，0.7 至 1.6），而安慰剂组改善了 1.5（95%CI，1.0 至 2.0）（差异-0.4，95%CI，-0.8 至 0.1，p=0.13）。虽然治疗组的关键次要结局没有统计学差异，但在预先指定的接受研究药物治疗组（n=37）中观察到了益处。对于这个早期治疗组，在第一周内观察到疾病严重程度、第 3 天和第 7 天的患者报告功能以及完全康复方面有临床意义的差异。没有死亡或治疗中出现的严重不良事件。
对于急诊室治疗蛇咬伤，在抗蛇毒血清的基础上添加瓦瑞沙帕丁并没有发现基于 SSS 的主要结局的差异证据。在被蛇咬伤后 5 小时内开始治疗的患者中观察到了潜在的有益信号。
