Efficacy and Safety of Moxidectin-Albendazole and Ivermectin-Albendazole Combination Therapy Compared to Albendazole Monotherapy in Adolescents and Adults Infected with Trichuris trichiura: A Randomized, Controlled Superiority Trial

Abstract

Background: The currently recommended benzimidazole monotherapy is insufficiently effective to control infection with the soil-transmitted helminth Trichuris trichiura. Ivermectin-albendazole combination has shown promising, but setting-dependent efficacy, with therapeutic underperformance in Côte d'Ivoire. We evaluated whether moxidectin-albendazole could serve as an alternative to albendazole monotherapy in Côte d'Ivoire.

Methods: In this community-based, randomized, placebo-controlled, parallel-group superiority trial, individuals aged 12-60 years were screened for T. trichiura eggs in their stool using quadruplicate Kato-Katz thick smears. Diagnostically and clinically eligible participants were randomly assigned (1:1:1) to receive single oral doses of moxidectin (8 mg) and albendazole (400 mg), ivermectin (200 µg/kg) and albendazole (400 mg), or albendazole (400 mg) and placebo. The primary outcome was proportion cured, ie, cure rate (CR), assessed at 2-3 weeks post-treatment. Safety endpoints were assessed pre-treatment and at 3 and 24 hours post-treatment.

Results: For the 210 participants with primary outcome data, we observed CRs of 15.3% in the moxidectin-albendazole arm and 22.5% in the ivermectin-albendazole arm, which did not differ significantly from the CR of 13.4% in the albendazole arm (differences: 1.8%-points [95% confidence interval: -10.1 to 13.6] and 9.1%-points [-3.9 to 21.8], respectively). Most common adverse events were abdominal pain (range across arms: 11.9%-20.9%), headache (4.7%-14.3%), and itching (5.8%-13.1%), which were predominantly mild and transient.

Conclusions: All therapies showed similar low efficacy in treating trichuriasis in Côte d'Ivoire. Alternative treatment options need to be evaluated, and further analyses should be conducted to understand the lack of enhanced activity of the combination therapies in Côte d'Ivoire.

Clinical trials registration: NCT04726969.

Keywords: Trichuris trichiura; albendazole; ivermectin; moxidectin; soil-transmitted helminths.