Fixed-dose albendazole–ivermectin combo shows promise in T. trichiura, hookworm infections

A single-pill combination that contains albendazole and ivermectin is superior to albendazole alone for treating Trichuris trichiura and hookworm infections, with similar safety profiles, according to data from a phase II/III trial.

The trial included 1,001 participants (54 percent male) aged 5–18 years and weighing at least 15 kg who were infected with T. trichiura, hookworms, or S. stercoralis. These participants were randomly assigned to receive a single dose of a fixed-dose combination (FDC×1) of albendazole (400 mg) plus ivermectin (9 mg or 18 mg), three consecutive daily doses of an FDC (FDC×3) of albendazole (400 mg) plus ivermectin (9 mg or 18 mg), or a single dose of albendazole alone (400 mg). Clinicians assessing the outcomes were blinded to the treatment assignment, but participants and those administering the treatments were not.

The primary outcome in phase II was safety during the first 3 hours after the intervention and for 7 days, while the primary outcome in phase III was efficacy (ie, the number of participants cured at day 21 out of the total number infected at baseline) for T. trichiura. Both outcomes were assessed in the intention-to-treat population.

Of the participants, 636 (64 percent) were infected with T. trichiura, 360 (36 percent) with hookworm, and 104 (10 percent) with S. stercoralis. The remaining 94 (9 percent) participants had co-infections and were included in the analysis of each infecting species. The albendazole arm consisted of 243 participants, the FDC×1 arm comprised 381, and the FDC×3 arm included 377.

In both phase II and III, the most common mild-to-moderate adverse events in the FDC groups was gastrointestinal symptoms, which resolved within 48 hours without intervention. At least one treatment-related adverse was recorded in 34 participants (14 percent) in the albendazole arm, 75 (20 percent) in the FDC×1 arm, and 88 (23 percent) in the FDC×3 arm. There were no reports of any serious adverse events.

For T. trichiura, the cure rate was higher in both FDC arms than in the albendazole arm (97.2 percent with FDC×3 and 82.9 percent with FDC×1 vs 35.9 percent; absolute differences, 61.3 percent and 47.0 percent, respectively). For hookworms, the cure rate was higher with FDC×3 vs albendazole (95.0 percent vs 65.1 percent; absolute difference, 29.9 percent) but did not differ between FDC×1 and albendazole (79.8 percent vs 65.1 percent).

The sample size for efficacy evaluation of S. stercoralis was not met.