Effectiveness of calcium channel blockade for organophosphorus and carbamate pesticide poisoning - study protocol for an open label, pragmatic, 3-arm RCT repurposing two widely available medicines
Effectiveness of calcium channel blockade for organophosphorus and carbamate pesticide poisoning - study protocol for an open label, pragmatic, 3-arm RCT repurposing two widely available medicines
复制标题
DOI：
10.1080/24734306.2023.2272073
复制
发表时间：
2023-12-31
影响因子：
--
通讯作者：
Eddleston，Michael
中科院分区：
文献类型：
--
作者：
Rabbi Chowdhury，Fazle;Shaw，Suvodip;Eddleston，Michael
农药自我中毒是全球三种最重要的自杀方式之一，每年估计有110- 168，000人死亡，其中大部分在贫穷的亚洲农村社区。有机磷（OP）和氨基甲酸酯抗胆碱酯酶杀虫剂是造成这些死亡的三分之二。钙通道阻断药物（CCB）可以减少农药的影响，防止死亡。两项临床前啮齿动物研究和八项分别使用尼莫地平和硫酸镁（MgSO 4）的临床研究显示了混合结果。我们已经建立了一个多中心随机对照试验（RCT）的患者与OP或氨基甲酸盐自我中毒承认在孟加拉国至少六家大医院。该研究计划在4年内招募最多3，243名患者。随机选择的三分之一的患者将接受标准治疗，三分之一将接受额外的尼莫地平治疗，三分之一将接受额外的MgSO 4治疗。额外治疗将持续48 h。我们将检查三组的死亡率（目前估计有11%的人死于标准治疗）和对机械通气的重症监护需求。这可能导致50年来第一种抗胆碱酯酶中毒的新疗法的开发，并将其引入全球常规医院实践。
Pesticide self-poisoning is one of the three most important global means of suicide, killing an estimated 110–168,000 people each year, mostly in poor rural Asian communities. Organophosphorus (OP) and carbamate anticholinesterase insecticides are responsible for about two-thirds of these deaths. Calcium channel blocking medicines (CCB) may reduce the effect of pesticides and prevent deaths. Two preclinical rodents’ studies and eight clinical studies utilising nimodipine and magnesium sulphate (MgSO4), respectively, showed mixed results. We have established a multi-centre randomised controlled trial (RCT) of patients with OP or carbamate self-poisoning admitted to at least six major hospitals in Bangladesh. The study aims to recruit maximum 3,243 patients over four years. One-third of the patients selected at random will receive standard treatment, while one-third will be treated with additional nimodipine and one-third with additional MgSO4. The additional treatments will be given for 48 h. We will check mortality (currently an estimated 11% die with standard treatment) and need for intensive care for mechanical ventilation across the three groups. This could lead to development of the first novel treatment for anticholinesterase poisoning in 50 years and its introduction into routine hospital practice worldwide.