A fixed-dose combination (FDC) of albendazole and ivermectin has shown promising results in treating soil-transmitted helminths (STH), offering a more effective tool against intestinal infections, according to a Phase II/III clinical trial. The study, published in The Lancet Infectious Diseases, highlights the potential of this combination to improve control of neglected tropical diseases.
Superior Efficacy Against Key Worm Species
The trial, conducted by the STOP consortium and led by the Barcelona Institute of Global Health (ISGlobal), assessed the safety and efficacy of the FDC in school-aged children across Ethiopia, Kenya, and Mozambique. Participants were infected with Trichuris trichiura, hookworm (Ancylostoma duodenale and Necator americanus), Strongyloides stercoralis, or a combination of these.
Of the 1,001 participants, approximately 64% were infected with T. trichiura, 36% with hookworm, and 10% with S. stercoralis. The study compared a single dose of albendazole alone, a single dose of the FDC (albendazole 400 mg plus ivermectin 9 mg or 18 mg), and three consecutive daily doses of the FDC.
Key Findings from the ALIVE Trial
The results indicated that for T. trichiura, the FDC groups had significantly higher cure rates compared to albendazole alone (97.2% for the three-dose FDC and 82.9% for the single-dose FDC vs. 35.9% for albendazole). Similarly, for hookworms, the three-dose FDC showed a higher cure rate (95.0%) than albendazole alone (65.1%), while the single-dose FDC had a comparable cure rate (79.8%).
"Treatments for soil-transmitted helminthiases face challenges, especially in addressing Trichuris trichiura. Combination regimens, particularly of ivermectin and albendazole, are promising," noted the research team, led by ISGlobal in Spain.
Addressing Limitations of Current Treatments
The current strategy against STH infections primarily involves regular deworming treatments with albendazole. However, albendazole's efficacy against T. trichiura has been declining, potentially due to emerging drug resistance. Furthermore, albendazole is not effective against Strongyloides stercoralis. The albendazole-ivermectin combination addresses these gaps, with ivermectin demonstrating greater efficacy against T. trichiura when combined with albendazole and serving as the drug of choice for S. stercoralis.
Implications for Public Health
Alejandro Krolewiecki, clinical trial leader, stated, "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."
The EMA’s human medicines committee (CHMP) has adopted a positive scientific opinion for Ivermectin/Albendazole for the treatment of infections caused by several types of worm parasites including lymphatic filariasis, a neglected tropical disease. The development of Ivermectin/Albendazole holds a high public health value as it will bring concrete advantages to the effectiveness of mass administration programmes in countries where these diseases are endemic. It will help reduce the risk of incorrect dosage, improve adherence, and reduce manufacturing and transport costs, ultimately allowing more people to be treated.
The trial's findings suggest that a single-dose regimen of the FDC could simplify mass deworming activities, while the three-day regimen, offering superior efficacy, may be more suitable for individual treatment decisions or programs aiming for complete elimination of STH from the population. Further studies are underway to evaluate the safety of the FDC in mass deworming campaigns.
