This project will test the safety and efficacy of combining two drugs (ivermectin and albendazole) for the treatment of parasitic worms that live in the intestine of up to one fifth of the world’s population.
Children infected with SSTH suffer from malnutrition and growth impairment. Additionally, hookworm and whipworm infections can cause anaemia, which is detrimental not only for children, but also pregnant women and women of reproductive age.
The current strategy to control STH in endemic areas is mass drug administration of albendazole or mebendazole, mainly to pre-school and school-aged children and regardless of their infection status. Although treatment works well for some species including roundworm (Ascaris lumbricoides) and hookworms (Necator americanus and Ancylostoma duodenale), its efficacy against whipworm (Trichuris trichiura) is poor and it is not effective against threadworm (Strongyloides stercoralis).
Therefore, new drugs, or drug combinations, are an urgent priority to increase the effectiveness of control programmes. The World Health Organization has recently recommended that ivermectin might be used in combination with albendazole to increase effectiveness against whipworm and threadworm. Both drugs are safe, and can be taken at the same time.
We propose to combine ivermectin with albendazole in a single tablet, suitable for all age groups (known as a fixed dose co-formulation or FDC).
The central pillar of this four-year project is the ALIVE clinical trial, which will compare the safety and efficacy of this new combination, given on one day or on three consecutive days, as compared to the current standard of care (albendazole).
The clinical trial will be conducted in Kenya, Mozambique and Ethiopia, three African countries with moderate to high prevalence of these parasitic worm diseases. We plan to enrol and treat 1800 children.
Combining albendazole and ivermectin would not only increase overall efficacy, but would also help prevent the emergence of drug resistance in these worms, for which we currently do not have an alternative treatment.
Furthermore, combining two drugs at a fixed dose in one single pill has a series of advantages over giving two separate pills: it reduces the risk of incorrect dosage, it helps ensure adherence to treatment, and it simplifies drug administration and transport. The FDC also has lower manufacturing and packaging costs. All these benefits could translate into treating more people.
If successful, the new combination could greatly contribute to reducing the disease burden of these neglected diseases.