A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning

Date

2009-08-20

Authors

Perera, Polwattage MS
Jayamanna, Shaluka F
Hettiarachchi, Raja
Abeysinghe, Chandana
Karunatilake, Harindra
Dawson, Andrew H
Buckley, Nicholas

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BioMed Central

Abstract

BACKGROUND An estimated 2-3 million people are acutely poisoned by organophosphorus pesticides each year, mostly in the developing world. There is a pressing need for new affordable antidotes and clonidine has been shown to be effective in animal studies. Our aim was to determine the safety of clonidine given as an antidote in adult patients presenting with signs or symptoms of acute organophosphate ingestion. METHODS This study was a dose finding, open-label, multicentre, phase II trial. Forty eight patients with acute organophosphate poisoning were randomized to receive either clonidine or placebo: Four to receive placebo and twelve to receive clonidine at each dose level. The first dose level was an initial loading dose of 0.15 mg followed by an infusion of 0.5 mg of clonidine over 24 hours. The initial loading dose was increased to 0.3 mg, 0.45 and 0.6 mg. at all dosing levels however the subsequent infusion remained at 0.5 mg of clonidine over 24 hours. RESULTS The baseline characteristics of both groups were similar. The trial was stopped after completion of the 3rd dosing level. At the 1st and 2nd dosing level there were no reported adverse drug reactions. At the 3rd dosing level 5 patients (42%) developed significant hypotension during clonidine treatment that responded to intravenous fluids. There were no statistical differences in ventilation rate, pre and post GCS, and mortality rates over all levels. CONCLUSION Our findings suggest use of moderate doses of clonidine in acute organophosphate poisoning can be used without causing frequent clinical problems but that higher doses are associated with a high incidence of hypotension requiring intervention. Further studies are needed to study the efficacy of clonidine as an antidote in organophosphate poisoning.

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Keywords

acute disease, adult, antidotes, clonidine, female, humans, male, middle aged, pesticides, organophosphate poisoning

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Trials

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Journal article

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