An Open Label Randomized Comparative Study to Assess the Efficacy and Tolerability of Eurartesim® Versus Chloroquine and Nonrelapse Therapy With Primaquine for Uncomplicated Plasmodium Vivax Monoinfection Malaria

Brief Summary

Detailed Description

Dihydroartemisinin/Piperaquine (DHA-PQP or Eurartesim®) is recommended by World Health Organization Expert Board for the treatment of P.vivax malaria, in case of chloroquine-resistance (CQR). However, no clinical study has been conducted to assess the efficacy of DHA-PQP in P.vivax malaria in the Americas. According a study performed in Amazonas state, Brazil, Artesunate/Amodiaquine (ASAQ) exhibited high efficacy against CQ resistant Plasmodium vivax and is an adequate alternative in the study area. They recommend other studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Other publication, a meta-analysis of randomized controlled trials, found nine publications from January 1989 to May 2013 in which DHA-PQP was more efficacious than CQ and Artemether/Lumefantrine in treating uncomplicated P. vivax malaria. However, this drug combination is not active against the hypnozoite stage of P. vivax. So, more efforts are required to establish how best combine this treatment with appropriate nonrelapse therapy. In 2015, primaquine was assessed in high dose for 14 days as treatment for the hypnozoite forms with DHA-PQP or artesunate-pyronaridine (AS-PYR). Both the treatment arms offer evidence of good tolerability and efficacy. In other previous study performed in an area with high chloroquine-resistance (Southern Papua, Indonesia), DHA-PQP was compared to ASAQ, but never compared to chloroquine by itself in areas where chloroquine still works. The objectives of this trial are to demonstrate the superiority of adequate parasitological response at D42 of Dihydroartemisinin plus Piperaquine versus Chloroquine and to evaluate the proportion of failure until D180 considering different starting days of Primaquine (0.50 mg/kg/day) for 14 days. This clinical trial will be undertaken in the Amazonas State (Western Brazilian Amazon), in Manaus, at Fundação de Medicina Tropical Dr Heitor Vieira Dourado. The climate is tropical, with mean temperatures between 26°C and 30°C. It is a prospective, open-label, 4-arm, randomized and comparison trial. One hundred and fifteen (115) patients were planned to be enrolled in each treatment arm (after a preliminary analysis this number was increased to 184; total number of participants: 563). In this protocol, all the subjects will be screened to evaluate Glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency and the laboratorial tests (specially haemoglobin) in all the visits will be evaluated, as well. The referred deficiency is estimated to be 3% among men from the Amazon and essentially the A-type (african type), which leads to moderate deficiency and minor clinical complications. Each dose of the schizonticidal treatment will be administered by a study pharmacist, and the patient will be monitored for 30 minutes after administration. The assessment schedule will be done in days 1, 2, 3, 5, 7, 14, 21, 28, 42, 63, 90, 120, 150 and 180 (in addition, patient will be asked to come back to the health centre if fever occurs at any time).

Primary Outcomes

Secondary Outcomes

• Number of participants with negative parasitological test(6 months (for this analysis will not be considered the primary outcomes dates (Day42 and D180))
• Number of participants with any treatment-related adverse event of clinical tolerability(6 months)
• Number of participants with any biological intolerability(Until Day 28)
• Number of participants with treatment-related prolonged QT interval.(Day 3)