Prevention of Acute Adverse Reactions to Antivenom in Snakebite: Interim Report of Blinded Data from a Randomised, Controlled Trial

De Silva HA1, Ranasinha CD1, Pathmeswaran A1, Lalloo D2, Armitage J3, Aronson JK3, De Silva HJ1 1Clinical Trials Unit, University of Kelaniya, Sri Lanka. 2Liverpool School of Tropical Medicine, Liverpool, UK, 3University of Oxford, UK.

The annual incidence of snakebite in Sri Lanka exceeds 400/100,000 population. Polyvalent antivenom (AV) is widely available in Sri Lanka, but acute adverse reactions to it are common.

A multicentre, double-blind, randomised, placebo-controlled clinical trial is underway in three hospitals to determine whether low-dose adrenaline, promethazine, and hydrocortisone, alone and in different combinations, are significantly better than placebo in the prevention of severe reactions to antivenom in snakebite patients (NCT00270777). The study is designed to recruit 1000 patients. Eligible patients are randomised in a factorial (2 x 2 x 2) blinded design between one of eight combinations of trial medicines/placebo prior to AV administration. All trial patients are given 10 vials of AV by intravenous infusion, and monitored for acute adverse reactions for at least 96 hours.

Blinded trial data made available to the trial steering committee after three interim analyses are presented. Of 2943 snakebite victims presenting to study hospitals, 600 have been recruited in the first 18 months. The major reason for exclusion was absence of indication for AV (>90%). 74% recruited were transfers from rural hospitals; of these 35% had already received AV. The snake was identified in only 25% of cases; Russell’s viper accounted for >80% of these. Nine patients have died during the trial. Severe adverse reactions to AV occurred in 46%, moderate reactions in 31%, and only 18% had no reaction.

About 20% of snakebites presenting to the study hospitals require AV. Only a third who need AV receive it early at rural hospitals. Low species identification makes polyvalent AV more appropriate than monovalent AV in our setting. However, adverse reactions to polyvalent AV available here are extremely common. These highlight the importance of this trial that aims to improve safety of the available polyvalent AV.