Tesfay AbrehaBereket AlemayehuAshenafi AssefaGhulam Rahim AwabJ. Kevin BairdBeay BezabihPhaik Yeong CheahNicholas P. DayAngela DevineMehul DordaArjen M. DondorpSamuel GirmaTran Tinh HienDaddi JimaMoges KassaAmha KebendeNaw Htee KhuToby LeslieBenedikt LeyYoel LubellIsmail MayanZenebe MeakuAyodhia P. PasaribuNguyen Hoan PhuRic N. PriceJulie A. SimpsonHiwot SolomonInge SutantoYehualahet TadesseBob TaylorNgo Viet ThanhKamala ThriemerLorenz von SeidleinNicholas WhiteAdugna WoyessaPrayoon YuentrakulRohullah ZekriaColumbia University Mailman School of Public HealthColumbia University Medical CenterEthiopian Public Health InstituteNangarhar Medical Faculty of Nangarhar UniversityEijkman-Oxford Clinical Research UnitNuffield Department of Clinical MedicineAmhara Regional Health BureauMahidol UniversityWorldwide Antimalarial Resistance Network (WWARN)UCLLondon School of Hygiene & Tropical MedicineHealth Protection and Research OrganizationMenzies School of Health ResearchUniversitas Sumatera UtaraUniversity of MelbourneFederal Ministry of Health - EthiopiaUniversitas Indonesia2018-11-232018-11-232015-12-07BMC Infectious Diseases. Vol.15, No.1 (2015)147123342-s2.0-84952865125https://repository.li.mahidol.ac.th/handle/20.500.14594/36220© 2015 The IMPROV Study Group. Background: Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. Design: This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8 weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. Discussion: This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir. Trial registration: ClinicalTrials.gov Identifier: NCT01814683. Registered March 18, 2013Mahidol UniversityMedicineArticleSCOPUS10.1186/s12879-015-1276-2