Wendelin Moser1, Said M Ali2, Shaali M Ame2, Benjamin Speich1, Maxim Puchkov3, Jörg Huwyler3, Marco Albonico4, Jan Hattendorf5, Jennifer Keiser6. 1. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland. 2. Laboratory Division, Public Health Laboratory-Ivo de Carneri, Chake Chake, Tanzania. 3. Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland. 4. Ivo de Carneri Foundation, Milan, Italy. 5. Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland. 6. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland. Electronic address: jennifer.keiser@unibas.ch.
Abstract
BACKGROUND: Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura. Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura. We aimed to assess the nature of the dose-response relation to determine the optimum dose. METHODS: We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6-14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5-30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura, both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231. FINDINGS: Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or theplacebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11-36]; egg-reduction rate 85·0%, 64·5-92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44-65) with an egg-reduction rate of 97·5% (94·4-98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43-73) with an egg-reduction rate of 98·8% (96·8-99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment. INTERPRETATION: Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura. An optimum therapeutic dose range of 15-30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7-14 years in sub-Saharan Africa would receive doses of 11·7-32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. FUNDING: Swiss National Science Foundation.
RCT Entities:
BACKGROUND: Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura. Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura. We aimed to assess the nature of the dose-response relation to determine the optimum dose. METHODS: We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6-14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5-30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura, both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231. FINDINGS: Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or the placebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11-36]; egg-reduction rate 85·0%, 64·5-92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44-65) with an egg-reduction rate of 97·5% (94·4-98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43-73) with an egg-reduction rate of 98·8% (96·8-99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment. INTERPRETATION: Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura. An optimum therapeutic dose range of 15-30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7-14 years in sub-Saharan Africa would receive doses of 11·7-32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. FUNDING: Swiss National Science Foundation.
Authors: Frederick A Partridge; Emma A Murphy; Nicky J Willis; Carole J R Bataille; Ruth Forman; Narinder Heyer-Chauhan; Bruno Marinič; Daniel J C Sowood; Graham M Wynne; Kathryn J Else; Angela J Russell; David B Sattelle Journal: PLoS Negl Trop Dis Date: 2017-02-09
Authors: Marta S Palmeirim; Eveline Hürlimann; Stefanie Knopp; Benjamin Speich; Vicente Belizario; Serene A Joseph; Michel Vaillant; Piero Olliaro; Jennifer Keiser Journal: PLoS Negl Trop Dis Date: 2018-04-27
Authors: Benjamin Speich; Wendelin Moser; Said M Ali; Shaali M Ame; Marco Albonico; Jan Hattendorf; Jennifer Keiser Journal: Parasit Vectors Date: 2016-03-02 Impact factor: 3.876