SCHISTOACT: A protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of Praziquantel plus Artemisinin-based combinations in the treatment of Schistosoma mansoni infection

Abstract

Abstract Background: Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya. Methods: The SCHISTOACT study is an open-label, head-to-head, five-arm, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-age children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine; or artesunate-amodiaquine; or artesunate plus mefloquine; or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at -10 for the risk difference in cure rates between praziquantel and the combined treatment. Discussion: This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases. Trial registration: Pan-African Clinical Trials Registry: PACTR202001919442161. Retrospectively registered on 6 January 2020. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9591