Treatments for soil-transmitted helminthiases face challenges, especially in addressing\ Trichuris trichiura. Combination regimens, particularly of ivermectin and albendazole, are promising. We aimed to assess the safety, efficacy, and palatability of a combination tablet for the treatment of\ T trichiura, hookworm, and\ Strongyloides stercoralis\ infections among school-aged children in Ethiopia, Kenya, and Mozambique.
We conducted an adaptive phase 2/3, randomised, parallel-group, active-controlled, superiority trial in 15 schools in Ethiopia, Kenya, and Mozambique. Eligible participants for both phases were aged 5{\textendash}18 years, weighed at least 15 kg, and were infected with\ T trichiura, hookworms, or\ S stercoralis. Participants were randomly assigned via a computer-generated sequence to either a single dose of a fixed-dose combination (FDC{\texttimes}1) of albendazole (400 mg) plus ivermectin (9 mg or 18 mg), three consecutive daily doses of an FDC (FDC{\texttimes}3) of albendazole (400 mg) plus ivermectin (9 mg or 18 mg), or a single dose of albendazole alone (400 mg) via block randomisation, stratified by soil-transmitted helminth species. Participants and those administering the treatments were not masked to treatment assignment, but those assessing the outcomes were masked. The primary outcome of phase 2 (conducted in Kenya only) was safety during the first 3 h after the intervention and for 7 days, and the primary outcome of phase 3 was efficacy (ie, the proportion of individuals cured at day 21 out of the total number infected at baseline) for\ T trichiura; both primary outcomes were analysed in the intention-to-treat population. This trial is registered with\ ClinicalTrials.gov,\ NCT05124691, and is terminated.
Between Jan 20, 2022, and March 24, 2023, 1001 participants were recruited (465 [46\%] were female and 536 [54\%] were male). 636 (64\%) were infected with\ T trichiura, 360 (36\%) with hookworm, and 104 (10\%) with\ S stercoralis; 94 (9\%) of 1001 participants had co-infections and were included in the analysis of each infecting species. A total of 243 participants were allocated to the albendazole group, 381 to the FDC{\texttimes}1 group, and 377 to the FDC{\texttimes}3 group. In both phase 2 and 3, gastrointestinal symptoms were the most common mild-to-moderate adverse events in the FDC groups, but resolved within 48 h without intervention. At least one treatment-related adverse event occurred in 34 (14\%) of 243 participants in the albendazole group, 75 (20\%) of 381 participants in the FDC{\texttimes}1 group, and 88 (23\%) of 377 participants in the FDC{\texttimes}3 group. No serious adverse events occurred. For\ T trichiura, both FDC groups had a higher cure rate (97{\textperiodcentered}2\% [95\% CI 95{\textperiodcentered}2{\textendash} 99{\textperiodcentered}3] for FDC{\texttimes}3 and 82{\textperiodcentered}9\% [78{\textperiodcentered}2{\textendash}87{\textperiodcentered}5] for FDC{\texttimes}1) than albendazole (35{\textperiodcentered}9\% [27{\textperiodcentered}7{\textendash}44{\textperiodcentered}1]), with absolute differences of 61{\textperiodcentered}3\% (98\% CI 50{\textperiodcentered}2{\textendash}71{\textperiodcentered}2) and 47{\textperiodcentered}0\% (34{\textperiodcentered}7{\textendash}58{\textperiodcentered}1), respectively. For hookworms, FDC{\texttimes}3 had a higher cure rate (95{\textperiodcentered}0\% [95\% CI 91{\textperiodcentered}1{\textendash}98{\textperiodcentered}9]) than albendazole (65{\textperiodcentered}1\% [56{\textperiodcentered}0{\textendash}74{\textperiodcentered}2]), with absolute differences of 29{\textperiodcentered}9\% (98\% CI 17{\textperiodcentered}2{\textendash}42{\textperiodcentered}4), whereas FDC{\texttimes}1 had a similar cure rate (79{\textperiodcentered}8\% [72{\textperiodcentered}8{\textendash}86{\textperiodcentered}9]) to albendazole. The sample size for efficacy evaluation of\ S stercoralis\ was not met.
An FDC of albendazole plus ivermectin has a similar safety profile but superior efficacy to albendazole alone against\ T trichiura\ infection and hookworms. These findings open opportunities for control of all soil-transmitted helminth species of interest, including potentially\ S stercoralis. Evaluation of safety in larger populations and implementation scenarios are the next steps for this innovation to promote its incorporation into programmatic activities.
}, year = {2025}, journal = {The Lancet Infectious Diseases}, volume = {25}, pages = {548-559}, publisher = {Elsevier BV}, issn = {1473-3099}, url = {https://www.sciencedirect.com/science/article/abs/pii/S1473309924006698}, doi = {10.1016/s1473-3099(24)00669-8}, language = {eng}, }