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Tafenoquine versus primaquine to prevent relapse of plasmodium vivax malaria

dc.contributor.authorAlejandro Llanos-Cuentasen_US
dc.contributor.authorMarcus V.G. Lacerdaen_US
dc.contributor.authorTran T. Hienen_US
dc.contributor.authorIván D. Vélezen_US
dc.contributor.authorChayadol Namaik-Larpen_US
dc.contributor.authorCindy S. Chuen_US
dc.contributor.authorMaria F. Villegasen_US
dc.contributor.authorFernando Valen_US
dc.contributor.authorWuelton M. Monteiroen_US
dc.contributor.authorMarcelo A.M. Britoen_US
dc.contributor.authorMônica R.F. Costaen_US
dc.contributor.authorRaul Chuquiyaurien_US
dc.contributor.authorMartín Casapíaen_US
dc.contributor.authorChau H. Nguyenen_US
dc.contributor.authorSandra Aruachanen_US
dc.contributor.authorRatchadaporn Papwijitsilen_US
dc.contributor.authorFrançois H. Nostenen_US
dc.contributor.authorGermana Banconeen_US
dc.contributor.authorBrian Angusen_US
dc.contributor.authorStephan Duparcen_US
dc.contributor.authorGraham Craigen_US
dc.contributor.authorVictoria M. Rousellen_US
dc.contributor.authorSiôn W. Jonesen_US
dc.contributor.authorElizabeth Hardakeren_US
dc.contributor.authorDonna D. Cloveren_US
dc.contributor.authorLindsay Kendallen_US
dc.contributor.authorKhadeeja Mohameden_US
dc.contributor.authorGavin C.K.W. Kohen_US
dc.contributor.authorViviana M. Wilchesen_US
dc.contributor.authorJohn J. Bretonen_US
dc.contributor.authorJustin A. Greenen_US
dc.contributor.otherGlaxoSmithKline, USAen_US
dc.contributor.otherUniversidad Peruana Cayetano Herediaen_US
dc.contributor.otherUniversidad de Antioquiaen_US
dc.contributor.otherUniversity of Oxforden_US
dc.contributor.otherFundacao Oswaldo Cruzen_US
dc.contributor.otherGlaxoSmithKline plc.en_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherMedicines for Malaria Ventureen_US
dc.contributor.otherIMAT Onco-medicaen_US
dc.contributor.otherCentro de Investigaciones Clínicasen_US
dc.contributor.otherOxford University Clinical Research Uniten_US
dc.date.accessioned2020-01-27T10:13:00Z
dc.date.available2020-01-27T10:13:00Z
dc.date.issued2019-01-17en_US
dc.description.abstractCopyright © 2019 Massachusetts Medical Society. BACKGROUND Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed “radical cure.” METHODS We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (3.0 g per deciliter or ≥30% from baseline or to a level of 6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin. RESULTS A protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, −4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96). CONCLUSIONS Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine.en_US
dc.identifier.citationNew England Journal of Medicine. Vol.380, No.3 (2019), 229-241en_US
dc.identifier.doi10.1056/NEJMoa1802537en_US
dc.identifier.issn15334406en_US
dc.identifier.issn00284793en_US
dc.identifier.other2-s2.0-85060127274en_US
dc.identifier.urihttps://repository.li.mahidol.ac.th/handle/123456789/51960
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060127274&origin=inwarden_US
dc.subjectMedicineen_US
dc.titleTafenoquine versus primaquine to prevent relapse of plasmodium vivax malariaen_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060127274&origin=inwarden_US

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