Efficacy and Safety of Co-Administered Ivermectin and Albendazole in School-Aged Children and Adults Infected With <i>Trichuris trichiura</i>: A Multi-Country Randomized Controlled Trial

Abstract

Background: Preventive chemotherapy with albendazole or mebendazole remains the cornerstone of soil-transmitted helminth control. However, these drugs are not effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence from varying settings and age classes is needed. Methods: We conducted three double-blinded, parallel-group, randomized controlled trials in community members aged 6-60 years infected with T. trichiura in Cote d’Ivoire, Laos and Pemba Island, Tanzania. Participants were randomly assigned using a computer-generated, stratified, block randomization code to either ivermectin (200 µg/kg) plus albendazole (400 mg) or the current standard (albendazole 400 mg). The primary outcome was cure rate (CR) against T. trichiura. Secondary outcomes were egg reduction rate (ERR) against T. trichiura, efficacy against co-infecting helminths and safety assessed three and 24 hours post-treatment. Findings: Data on treatment efficacy was available for 467, 407 and 581 participants in Cote d’Ivoire, Laos and Pemba Island, respectively. Ivermectin-albendazole showed significantly higher efficacy against T. trichiura than albendazole in Laos (CRs: 65.7% vs. 8.2%, difference (95% CI): 57.5 (49.5 to 64.5), p<0.001; ERRs: 99.2% vs. 68.8%) and Pemba Island (CRs: 48.6% vs. 6.1%, difference (95% CI): 42.5 (35.9 to 48.7), p<0.001; ERRs: 98.3% vs. 57.1%), but revealed similar efficacy in Cote d’Ivoire (CRs: 13.8% vs. 10.2%, difference (95% CI): 3.6 (-2.3 to 9.5), p=0.24; ERRs: 70.2% vs. 64.1%). Adverse events were reported by 14.0% and 13.6% of assessed participants 3h and 24h after treatment, respectively. Interpretation: Treatment with ivermectin–albendazole resulted in higher efficacy against trichuriasis in Laos and on Pemba Island, but not in Cote d’Ivoire. Further research is warranted on factors influencing ivermectin-albendazole efficacy and to identify more effective treatments. Clinical Trial Registration Details: The trials are registered at ClinicalTrials.gov, NCT03527732. Funding Information: Bill and Melinda Gates Foundation, reference number OPP1153928 Declaration of Interests: None to declare. Ethics Approval Statement: These trials were undertaken in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The protocol was approved by independent ethics committees in Cote d’Ivoire, Laos, Pemba (Zanzibar) and Switzerland. Participating adults or parents/guardians of participating children provided written informed consent. Children provided written (Cote d’Ivoire) or oral assent (Laos, Pemba).