Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration

Pere Millat-Martínez, Rhoda Ila, Moses Laman, Leanne Robinson, Harin Karunajeewa, Haina Abel, Kevin Pulai, Sergi Sanz, Laurens Manning, Brioni Moore, Quique Bassat, Oriol Mitjà

Research output: Contribution to journalArticle

Abstract

Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered for use as a tool for malaria elimination. As an effective and long-acting antimalarial, dihydroartemisinin-piperaquine (DHA-PQP) appears to be suitable as a candidate for MDA. However, the absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA. We conducted an interventional study in Lihir Island, Papua New Guinea, using healthy individuals age 3 to 60 years who received a standard 3-day course of DHA-PQP on 3 consecutive months. Twelve-lead electrocardiography (ECG) readings were conducted predose and 4 h after the final dose of each month. The primary safety endpoint was QT interval correction (QTc using Fridericia's correction [QTcF]) prolongation from baseline to 4 h postdosing. We compared the difference in prolongations between the third course postdose and the first course postdose. Of 84 enrolled participants, 69 (82%) participants completed all treatment courses and ECG measurements. The average increase in QTcF was 19.6 ms (standard deviation [SD], 17.8 ms) and 17.1 ms (SD, 17.1 ms) for the first-course and third-course postdosing ECGs risk difference, -2.4 (95% confidence interval [95% CI], -6.9 to 2.1; P = 0.285), respectively. We recorded a QTcF prolongation of >60 ms from baseline in 3 (4.3%) and 2 (2.9%) participants after the first course and third course (P = 1.00), respectively. No participants had QTcF intervals of >500 ms at any time point. Three consecutive monthly courses of DHA-PQP were as safe as a single course. The absence of cumulative cardiotoxicity with repeated dosing supports the use of monthly DHA-PQP as part of malaria elimination strategies.

Original languageEnglish
Article numbere01153-18
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

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dihydroartemisinin
Electrocardiography
Antimalarials
Safety
Malaria
Pharmaceutical Preparations
Papua New Guinea
Islands
Reading
Appointments and Schedules
Confidence Intervals
piperaquine

Cite this

Millat-Martínez, Pere ; Ila, Rhoda ; Laman, Moses ; Robinson, Leanne ; Karunajeewa, Harin ; Abel, Haina ; Pulai, Kevin ; Sanz, Sergi ; Manning, Laurens ; Moore, Brioni ; Bassat, Quique ; Mitjà, Oriol. / Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration. In: Antimicrobial Agents and Chemotherapy. 2018 ; Vol. 62, No. 12.
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Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration. / Millat-Martínez, Pere; Ila, Rhoda; Laman, Moses; Robinson, Leanne; Karunajeewa, Harin; Abel, Haina; Pulai, Kevin; Sanz, Sergi; Manning, Laurens; Moore, Brioni; Bassat, Quique; Mitjà, Oriol.

In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 12, e01153-18, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration

AU - Millat-Martínez, Pere

AU - Ila, Rhoda

AU - Laman, Moses

AU - Robinson, Leanne

AU - Karunajeewa, Harin

AU - Abel, Haina

AU - Pulai, Kevin

AU - Sanz, Sergi

AU - Manning, Laurens

AU - Moore, Brioni

AU - Bassat, Quique

AU - Mitjà, Oriol

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