Children in resource-limited rural areas are at a high risk of infection with Trichuris trichiura, a soil-transmitted helminth affecting up to 300 million people globally. Heavy infections can result in long-term morbidity, impairing physical and cognitive development. There is insufficient evidence on co-administration of ivermectin–albendazole in children younger than 6 years infected with T trichiura. We aimed to identify the optimal dose of ivermectin given as a new orodispersible tablet formulation (co-administered with 400 mg albendazole) in children aged 2–5 years with trichuriasis.

In this community-based, single-blind, randomised, controlled, parallel-group, dose-ranging, phase 2 trial conducted in communities on Pemba Island, Tanzania, children aged 2–5 years were screened for the presence of T trichiura eggs in their stool via quadruplicate Kato–Katz thick smears. Children who tested positive on at least two of four slides, did not present with any systemic or severe chronic illness, had not been treated with anthelmintic medication since diagnosis, and were willing to not self-treat with anthelmintics throughout the study were eligible for inclusion. With computer-generated group allocation (using block sizes of six and stratified by age and infection intensity), participants were randomly assigned (1:1:1:1:1:1) to single oral doses of placebo plus albendazole (400 mg), orodispersible ivermectin tablets (100 μg/kg, 200 μg/kg, 300 μg/kg, or 400 μg/kg) plus albendazole (400 mg), or standard ivermectin tablets (200 μg/kg) plus albendazole (400 mg). Participants and study team members evaluating outcomes were masked to treatment allocation. The primary endpoint was cure from T trichiura infection, defined as T trichiura egg-positive participants becoming egg-negative at 14–21 days post-treatment, assessed in the full analysis set (ie, all randomly assigned participants providing any primary endpoint data). The ivermectin dose–response curve was estimated with hyperbolic Emax models. Treatment-emergent adverse events were assessed as a secondary endpoint at 3 h, 24 h, and 14–21 days post-treatment in all participants who received study treatment. This trial is registered at ClinicalTrials.gov (NCT06184399), and is completed.

Between June 6 and July 4, 2024, 409 individuals were screened for eligibility, 260 of whom were randomly assigned to placebo plus albendazole, ascending doses of orodispersible ivermectin plus albendazole, or standard ivermectin plus albendazole (ranging from 42 to 44 participants per group). 123 (47%) of the 260 participants were male and 137 (53%) were female. The mean age of participants was 3·6 years (SD 1·1). The full analysis set consisted of 245 participants with primary outcome data. The Emax model predicted that the lowest dose of 100 μg/kg orodispersible ivermectin plus albendazole was superior to placebo plus albendazole, with a predicted cure rate of 54·2% (95% CI 41·1–66·7; 21 of 42 cured) versus 16·7% (8·2–31·0; seven of 40 cured). The dose–response curve increased incrementally across all doses tested, with a predicted cure rate of 90·9% (95% CI 81·8–95·7; 36 of 40 cured) in the 400 μg/kg orodispersible ivermectin plus albendazole group. The most common treatment-emergent adverse event was abdominal pain (in three [7%] of 44 participants with 100 μg/kg, one [2%] of 42 with 200 μg/kg, one [2%] of 44 with 300 μg/kg, and two [5%] of 44 with 400 μg/kg orodispersible ivermectin plus albendazole; three [7%] of 43 with placebo plus albendazole; and one [2%] of 43 with standard ivermectin plus albendazole).

In preschool-aged children with trichuriasis, orodispersible ivermectin showed an increasing cure rate with ascending doses, together with a dose-independent safety profile. Our study paves the way for phase 3 studies of this much needed therapeutic to eventually treat multiple neglected tropical diseases in paediatric populations.

Swiss National Science Foundation.