Efficacy and Safety of Ascending Dosages of Tribendimidine Against Hookworm Infections in Children: A Randomized Controlled Trial.

Abstract

The global strategy to control soil-transmitted helminthiasis is mainly focused on preventive chemotherapy with albendazole and mebendazole. We assessed the efficacy and safety of ascending tribendimidine doses against hookworm infections in African school-aged children, key information for the development of tribendimidine. We performed a single blind, randomized, controlled trial in Côte d'Ivoire between June and August 2017. Eligible participants were randomly assigned to placebo, 100, 200, or 400 mg tribendimidine. Cure rates (CRs, primary outcome) and egg reduction rates (ERRs) were determined 14-21 days after treatment. Clinical symptoms were assessed before treatment and adverse events monitored 3 and 24 hours posttreatment. CRs calculated for 130 children dose-dependently increased. The observed CRs were 20.6% (7/34), 21.2% (7/33), 38.7% (12/31), and 53.1% (17/32) for placebo, 100, 200, and 400 mg of tribendimidine, respectively. The Emax model predicted a placebo corrected net effect of 34.3 percentage points (95% confidence interval [CI], 13.3-54.4) for the 400-mg tribendimidine dose. The ERRs (geometric mean) were 30.6% (95% CI, -24.7 to 64.1), 65.4% (95% CI, 24.5-85.9), 82.1% (95% CI, 58.4-92.5) and 92.2% (95% CI, 81.0-97.1) for placebo, 100, 200, and 400 mg tribendimidine, respectively. The Emax model predicted an ERR of 95% at 500 mg. Only mild adverse events and no abnormal biochemical parameters were observed. A 400-mg dose of tribendimidine yielded the highest efficacy and was well tolerated. Because children were mostly lightly infected, further investigations with tribendimidine against moderate/heavy hookworm infection are needed. The trial is registered at www.isrctn.com number ISRCTN81391471.