Efficacy and safety of moxidectin-albendazole combination therapy for Trichuris trichiura infections in school-aged children: a double-blind, randomised, controlled, superiority trial.

BACKGROUND

Infection with the soil-transmitted helminth Trichuris trichiura affects up to 300 million people globally, with children in rural areas in less economically developed countries being most at risk. If untreated, infection compromises physical and cognitive development and leads to long-lasting morbidity. We assessed whether moxidectin co-administered with albendazole is superior to the recommended albendazole monotherapy in treating trichuriasis in school-aged children.

METHODS

This randomised, double-blind, parallel-group, superiority, phase 3 trial took place between May 14 and Aug 5, 2024, in the Piki administrative district primary school in the Wete district, Pemba Island, Tanzania. Children aged between 6 and 11 years were screened for the presence of T trichiura eggs in their stool via quadruplicate Kato-Katz thick smears. Using computer-generated group allocation (block randomisation stratified by infection intensity and age), parasitologically and clinically eligible participants (two or more of four slides positive for eggs) were randomly assigned in a 3:2:1 ratio to receive single oral doses of either moxidectin (4 mg [aged 6-7 years] and 8 mg [aged 8-11 years]) plus 400 mg albendazole, moxidectin placebo plus 400 mg albendazole, or moxidectin placebo plus albendazole placebo. The primary endpoint was cure rate, assessed at 14-21 days post-treatment, using the full analysis set population. Safety was formally assessed at 3 h, 24 h, and 14-21 days post-treatment. This trial is registered at ClinicalTrials.gov (NCT06188715) and is complete.

FINDINGS

272 participants were screened, and after 48 participants were excluded for not meeting eligibility criteria, 224 eligible participants were randomly assigned to moxidectin-albendazole (n=114 [51%]), albendazole (n=74 [33%]), or placebo (n=36 [16%]). Of the 224 participants, 129 (58%) were male and 95 (42%) were female, and the mean age was 8·0 years (SD 1·3). For the 213 participants with primary outcome data, we observed a cure rate of 69% (77 of 111) in the moxidectin-albendazole group, which was significantly higher than the cure rate of 16% (11 of 68) in the albendazole group (absolute difference 53·2 percentage points [95% CI 39·6-64·2]). The cure rate in the placebo group was 12% (four of 34). The most common treatment-emergent adverse events were abdominal pain (five [4%] of 114 with moxidectin-albendazole, two [3%] of 74 with albendazole, and one [3%] of 36 with placebo) and headache (two [2%] of 114, none, and one [3%] of 36, respectively), which were all mild and transient.

INTERPRETATION

Moxidectin-albendazole combination therapy was superior to albendazole monotherapy in terms of efficacy in the treatment of trichuriasis in school-aged children. Both treatments presented a similar safety profile to placebo. Our study paves the way for a much-needed well tolerated and effective alternative combination treatment for children with trichuriasis.

FUNDING

Swiss National Science Foundation (reference 320030_175585).