DHA-PQP vs Chloroquine and Primaquine for Radical Cure of Vivax Malaria in Brazil
- Conditions
- TherapeuticsMalaria, Vivax
- Interventions
- Drug: CQ coadministered with PQDrug: DHA-PQP coadministered with PQDrug: DHA-PQP and PQ starting on Day 42Drug: CQ and PQ starting on Day 42
- Registration Number
- NCT03208907
- Lead Sponsor
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
- Brief Summary
Plasmodium vivax can be cause of severe malaria and mortality. There are serious public health implications associated with cases of P. vivax resistant to Chloroquine in the Americas as well there are efforts of many countries to eliminate this disease. In this way, it is critically important to evaluate an alternative radical cure treatment efficient to amazon scenario. The objectives of this trial are to demonstrate the superiority of adequate parasitological response at D42 of Dihydroartemisinin plus Piperaquine (DHA-PQP or Eurartesim®) 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. It is an open, 4 arms, randomised, comparative trial. Total of 460 patients are initially planned to be included. To demonstrate the superiority of DHA-PQP compared to Chloroquine, the 95% confidence interval of the difference observed between both treatment success rates will be determined. Each recurrence will be passively and actively detected for 180 days.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 419
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CQ coadministered with PQ CQ coadministered with PQ Chloroquine was administered for 3 days according to the brazilian protocol and Primaquine was administered for 14 days (0.50mg/kg/day) DHA-PQP coadministered with PQ DHA-PQP coadministered with PQ Dihydroartemisinin/Piperaquine was administered according to the weight and Primaquine (0.50mg/kg/day) DHA-PQP and PQ starting on Day 42 DHA-PQP and PQ starting on Day 42 Dihydroartemisinin/Piperaquine was administered for 3 days according to the weight and Primaquine started on Day 42 for 14 days (0.50mg/kg/day) \[arm halted after preliminary analysis\] CQ and PQ starting on Day 42 CQ and PQ starting on Day 42 Chloroquine was administered for 3 days according to the brazilian protocol and Primaquine started on Day 42 for 14 days (0.50mg/kg/day) \[arm halted after preliminary analysis\]
- Primary Outcome Measures
Name Time Method Number of participants with negative parasitological test (schizonticidal therapy evaluation) Day 42 Schizonticidal efficacy will be assessed based on the absence of Vivax Plasmodium parasites in blood of the participants, confirmed by microscopy.
Number of participants with negative parasitological test (nonrelapse therapy evaluation) Day 180 Nonrelapse therapy efficacy will be assessed based on the absence of Vivax Plasmodium parasites in blood, confirmed by microscopy.
- Secondary Outcome Measures
Name Time Method Number of participants with negative parasitological test 6 months (for this analysis will not be considered the primary outcomes dates (Day42 and D180) Therapy efficacy will be assessed based on the presence or absence of Vivax Plasmodium parasites in blood, confirmed by the presence or absence of parasites in peripheral blood by microscopy.
Number of participants with any treatment-related adverse event of clinical tolerability 6 months The participants will be clinically monitored. In all the scheduled visits a study physician will evaluate and register the clinical exam, and also obtain and update the clinical history to describe any adverse event. The participants will have also a card with a 24h phone number to contact in case of clinical symptoms or others needing.
Number of participants with any biological intolerability Until Day 28 Evolution of haemoglobin levels until D28 will be monitored in all the scheduled visits and also on unscheduled visits.
Number of participants with treatment-related prolonged QT interval. Day 3 Electrocardiogram evaluation will be assessed after completion of schizonticidal treatment
Trial Locations
- Locations (1)
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
🇧🇷Manaus, Amazonas, Brazil