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Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study

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dc.contributor.author Llanos-Cuentas, Alejandro
dc.contributor.author Lacerda, Marcus V.
dc.contributor.author Rueangweerayut, Ronnatrai
dc.contributor.author Krudsood, Srivicha
dc.contributor.author Gupta, Sandeep K.
dc.contributor.author Kochar, Sanjay K.
dc.contributor.author Arthur, Preetam
dc.contributor.author Chuenchom, Nuttagarn
dc.contributor.author Mohrle, Jorg J.
dc.contributor.author Duparc, Stephan
dc.contributor.author Ugwuegbulam, Cletus
dc.contributor.author Kleim, Jorg-Peter
dc.contributor.author Carter, Nick
dc.contributor.author Green, Justin A.
dc.contributor.author Kellam, Lynda
dc.date.accessioned 2020-06-10T18:12:14Z
dc.date.available 2020-06-10T18:12:14Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/8062
dc.description.abstract BACKGROUND: Clinical effectiveness of previous regimens to treat Plasmodium vivax infection have been hampered by compliance. We aimed to assess the dose-response, safety, and tolerability of single-dose tafenoquine plus 3-day chloroquine for P vivax malaria radical cure. METHODS: In this double-blind, randomised, dose-ranging phase 2b study, men and women (aged >/=16 years) with microscopically confirmed P vivax monoinfection (parasite density >100 to <100,000 per muL blood) were enrolled from community health centres and hospitals across seven sites in Brazil, Peru, India, and Thailand. Patients with glucose-6-phosphate dehydrogenase enzyme activity of less than 70% were excluded. Eligible patients received chloroquine (days 1-3) and were randomly assigned (1:1:1:1:1:1) by a computer-generated randomisation schedule to receive single-dose tafenoquine 50 mg, 100 mg, 300 mg, or 600 mg, primaquine 15 mg for 14 days, or chloroquine alone. Randomisation was stratified by baseline parasite count (</=7500 and >7500 per muL blood). The primary efficacy endpoint was relapse-free efficacy at 6 months from initial dose (ie, clearance of initial infection without subsequent microscopically confirmed infection), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01376167. FINDINGS: Between Sept 19, 2011, and March 25, 2013, 329 patients were randomly assigned to a treatment group (chloroquine plus tafenoquine 50 mg [n=55], 100 mg [n=57], 300 mg [n=57], 600 mg [n=56]; or to chloroquine plus primaquine [n=50]; or chloroquine alone [n=54]). Relapse-free efficacy at 6 months was 57.7% (95% CI 43-70) with tafenoquine 50 mg, 54.1% (40-66) with tafenoquine 100 mg, 89.2% (77-95) with tafenoquine 300 mg, 91.9% (80-97) with tafenoquine 600 mg, 77.3% (63-87) with primaquine, and 37.5% (23-52) with chloroquine alone. Tafenoquine 300 mg and 600 mg had better efficacy than chloroquine alone (treatment differences 51.7% [95% CI 35-69], p<0.0001, with tafenoquine 300 mg and 54.5% [38-71], p<0.0001, with tafenoquine 600 mg), as did primaquine (treatment difference 39.9% [21-59], p=0.0004). Adverse events were similar between treatments. 29 serious adverse events occurred in 26 (8%) of 329 patients; QT prolongation was the most common serious adverse event (11 [3%] of 329), occurring in five (2%) of 225 patients receiving tafenoquine, four (8%) of 50 patients receiving primaquine, and two (4%) of 54 patients receiving chloroquine alone, with no evidence of an additional effect on QT of chloroquine plus tafenoquine coadministration. INTERPRETATION: Single-dose tafenoquine 300 mg coadministered with chloroquine for P vivax malaria relapse prevention was more efficacious than chloroquine alone, with a similar safety profile. As a result, it has been selected for further clinical assessment in phase 3. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof urn:issn:1474-547X
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Peru en_US
dc.subject Adolescent en_US
dc.subject Adult en_US
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Young Adult en_US
dc.subject Brazil en_US
dc.subject Aged en_US
dc.subject Middle Aged en_US
dc.subject Treatment Outcome en_US
dc.subject Drug Therapy, Combination en_US
dc.subject Double-Blind Method en_US
dc.subject Dose-Response Relationship, Drug en_US
dc.subject Thailand en_US
dc.subject India en_US
dc.subject Primaquine/therapeutic use en_US
dc.subject Antimalarials/administration & dosage en_US
dc.subject Aminoquinolines/administration & dosage en_US
dc.subject Chloroquine/therapeutic use en_US
dc.subject Malaria, Vivax/drug therapy/prevention & control en_US
dc.subject Secondary Prevention en_US
dc.title Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/S0140-6736(13)62568-4
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00

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