A new tablet that combines albendazole and ivermectin has shown to be both safe and more effective than albendazole alone in treating soil-transmitted helminths, according to the ALIVE clinical trial. This study was conducted by the STOP consortium and led by the Barcelona Institute of Global Health (ISGlobal), a center supported by 'la Caixa' Foundation, and the findings were recently published in The Lancet Infectious Diseases.
Soil-transmitted helminthiases (STH) are caused by four species of parasitic worms—Ascaris lumbricoides, Trichuris trichiura, Ancylostoma duodenale, and Necator americanus—and are transmitted through contact with contaminated soil or water. These infections affect around 1.5 billion people worldwide, impacting nutrition and health, particularly in children and women of reproductive age. The current control strategy relies on regular deworming with albendazole and improvements in water, sanitation, and hygiene. Yet albendazole’s efficacy against Trichuris trichiura has been declining, likely due to emerging drug resistance, and it is not effective against Strongyloides stercoralis, another helminth that requires control measures.
To address these gaps, the EDCTP-funded STOP consortium tested a fixed-dose co-formulation (FDC) of albendazole and ivermectin in the ALIVE trial, which took place in Ethiopia, Kenya, and Mozambique. Phase 2 of the trial focused on safety, enrolling a small number of participants in a staggered approach to monitor any adverse effects from higher-than-usual doses of ivermectin. No serious adverse effects were observed, and side effects resembled those in the albendazole group. Phase 3 then assessed efficacy and safety in a larger group of school-aged children (5 to 18 years old) with Trichuris trichiura, hookworms, Strongyloides stercoralis, or a combination of these parasites.
Children received either a single dose of albendazole, one dose of the new FDC (FDCx1), or three doses of the same FDC (FDCx3) over three consecutive days. Treatment efficacy was measured via cure rates—defined as no eggs found in stool samples post-treatment—and by reduction in egg counts. For Trichuris trichiura, FDCx3 achieved a cure rate of 97%, and FDCx1 reached 83%, compared to 36% with albendazole alone. For hookworms, the FDCx3 regimen showed a 95% cure rate, while FDCx1 was similar to albendazole.
“This fixed-dose co-formulation (FDC) has several advantages. It is easy to administer, as it is one single pill and does not require dose adjustments based on the child’s weight,” said Jose Muñoz, project leader and ISGlobal researcher. “Also, we hope that combining two drugs with different mechanisms of action will reduce the risk of the parasites becoming drug-resistant,” he added.
Even though the sample size was too small to assess efficacy conclusively for Strongyloides stercoralis, existing evidence suggests that ivermectin is far more effective than albendazole against this parasite. “This is a pivotal trial that opens up the possibility of controlling all species of STH, including Strongyloides, and may lead to reconsider elimination goals that were deemed unattainable with albendazole alone,” commented clinical trial coordinator Alejandro Krolewiecki.
Plans are underway to conduct larger-scale studies, such as the ongoing trial led by STOP2030, to further evaluate the safety of the FDC in mass deworming campaigns. Defining optimal implementation strategies for national programs will be key. A single-dose regimen may be simple to use in large-scale deworming efforts, while the three-day regimen—offering higher efficacy—could be useful for targeted treatment decisions or for programs seeking to eliminate STH entirely. “With its child-friendly formulation—orodispersible and mango-flavored—and its high acceptance, this tablet holds great potential for advancing health outcomes in regions affected by these diseases,” noted Stella Kepha from the Kenya Medical Research Institute (KEMRI).
This article was written in collaboration with generative AI company Alchemiq