Efficacy and safety of praziquantel plus Artemisinin-based combinations in the treatment of Kenyan children withSchistosoma mansoniinfection: an open-label, randomized, head-to-head, non-inferiority (SCHISTOACT) trial

Abstract

ABSTRACTBackgroundPraziquantel alone is insufficient for the control of schistosomiasis. Unlike praziquantel, artemisinin derivatives are effective for treating juvenile schistosome worms but not adult worms. Few studies have assessed the role of combination therapy, including praziquantel and artemisinin-based combinations, in treating schistosomiasis.MethodsA randomized, open-label, noninferiority trial was conducted in central Kenya to assess the efficacy and safety of praziquantel plus one of four artemisinin-based combination therapies in treating intestinal schistosomiasis. 540 children aged 9-15 years withSchistosoma mansoniinfection were randomly assigned (1:1:1:1:1) to receive a single oral dose of praziquantel (40mg/kg/day) alone or in combination with a 3-day course of artesunate plus sulfalene/pyrimethamine or artesunate plus amodiaquine or artesunate plus mefloquine or dihydroartemisinin-piperaquine. The primary endpoint was the cure rate assessed at six weeks in a per-protocol population. The noninferiority margin was defined as the lower limit of 95%CI of the risk difference in cure rates less than -10%.ResultsCure rates were available for 523 children. Overall, 82.5%, 81.7%, 76.2%, 88.7% and 85.7% of patients on praziquantel, praziquantel-artesunate-sulfalene/pyrimethamine, praziquantel-artesunate-amodiaquine, praziquantel-artesunate-mefloquine, and praziquantel-dihydroartemisinin-piperaquine, respectively, were cured. Non-inferiority was declared for praziquantel-artesunate-mefloquine (difference 6.2 [95%CI -3.3 to 15.6]) and praziquantel-dihydroartemisinin-piperaquine (3.2 [-6.7 to 13.1]) but not for praziquantel-artesunate-sulfalene/pyrimethamine (-0.8 [-11.2 to 9.6]) or praziquantel-artesunate-amodiaquine (-6.3 [-17.3 to 4.6]). A significantly lower number of adverse events were reported in the praziquantel arm than in the combined treatment arm. No serious adverse events were observed.ConclusionsPraziquantel-dihydroartemisinin-piperaquine and praziquantel-artesunate-mefloquine are suitable alternatives to praziquantel monotherapy. The role of artemisinin-based combinations in the treatment of intestinal schistosomiasis remains unclear.Clinical trials registrationPan-African Clinical Trials Registry, PACTR202001919442161.