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

Abstract

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.

Keywords:

• Organophosphate
• carbamate
• randomized control trial
• magnesium sulphate
• nimodipine

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the ACCORD, University of Edinburgh (Sponsor) and MRC JGHT [Reference: MR/S004947/1].