Publication:
Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial

Issued Date

2019-09-14

Resource Type

Article

ISSN

1474547X
01406736

DOI

10.1016/S0140-6736(19)31285-1

Other identifier(s)

2-s2.0-85071980923

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet. Vol.394, No.10202 (2019), 929-938

Suggested Citation

Walter R.J. Taylor, Kamala Thriemer, Lorenz von Seidlein, Prayoon Yuentrakul, Thanawat Assawariyathipat, Ashenafi Assefa, Sarah Auburn, Krisin Chand, Nguyen Hoang Chau, Phaik Yeong Cheah, Le Thanh Dong, Mehul Dhorda, Tamiru Shibru Degaga, Angela Devine, Lenny L. Ekawati, Fahmi Fahmi, Asrat Hailu, Mohammad Anwar Hasanzai, Tran Tinh Hien, Htee Khu, Benedikt Ley, Yoel Lubell, Jutta Marfurt, Hussein Mohammad, Kerryn A. Moore, Mohammad Nader Naddim, Ayodhia Pitaloka Pasaribu, Syahril Pasaribu, Cholrawee Promnarate, Awab Ghulam Rahim, Pasathron Sirithiranont, Hiwot Solomon, Herawati Sudoyo, Inge Sutanto, Ngo Viet Thanh, Nguyen Thi Tuyet-Trinh, Naomi Waithira, Adugna Woyessa, Fazal Yamin Yamin, Arjen Dondorp, Julie A. Simpson, J. Kevin Baird, Nicholas J. White, Nicholas P. Day, Ric N. Price Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial. The Lancet. Vol.394, No.10202 (2019), 929-938. doi:10.1016/S0140-6736(19)31285-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51415

Research Projects

Organizational Units

Authors

Journal Issue

Thesis

Title

Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial

Author(s)

Walter R.J. Taylor
 Kamala Thriemer
 Lorenz von Seidlein
 Prayoon Yuentrakul
 Thanawat Assawariyathipat
 Ashenafi Assefa
 Sarah Auburn
 Krisin Chand
 Nguyen Hoang Chau
 Phaik Yeong Cheah
 Le Thanh Dong
 Mehul Dhorda
 Tamiru Shibru Degaga
 Angela Devine
 Lenny L. Ekawati
 Fahmi Fahmi
 Asrat Hailu
 Mohammad Anwar Hasanzai
 Tran Tinh Hien
 Htee Khu
 Benedikt Ley
 Yoel Lubell
 Jutta Marfurt
 Hussein Mohammad
 Kerryn A. Moore
 Mohammad Nader Naddim
 Ayodhia Pitaloka Pasaribu
 Syahril Pasaribu
 Cholrawee Promnarate
 Awab Ghulam Rahim
 Pasathron Sirithiranont
 Hiwot Solomon
 Herawati Sudoyo
 Inge Sutanto
 Ngo Viet Thanh
 Nguyen Thi Tuyet-Trinh
 Naomi Waithira
 Adugna Woyessa
 Fazal Yamin Yamin
 Arjen Dondorp
 Julie A. Simpson
 J. Kevin Baird
 Nicholas J. White
 Nicholas P. Day
 Ric N. Price

Other Contributor(s)

Melbourne School of Population and Global Health
 Arba Minch University
 Federal Ministry of Health - Ethiopia
 Addis Ababa University
 Universitas Sumatera Utara
 Eijkman Institute for Molecular Biology
 Universitas Indonesia
 Menzies School of Health Research
 UCL
 Mahidol University
 Nuffield Department of Clinical Medicine
 Burnet Institute
 Krong-Pa Health Centre
 Ethiopian Public Health Institute
 Nangarhar University
 Eijkman Institute of Molecular Biology
 Health Protection and Research Organisation
 Health and Social Development Organization
 Institute of Malariology, Parasitology and Entomology

Abstract

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria. Methods: We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683). Findings: Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (−0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group). Interpretation: In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria. Funding: UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/51415

Collections

Scopus 2019