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    Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration

    Access Status
    Fulltext not available
    Authors
    Millat-Martínez, P.
    Ila, R.
    Laman, M.
    Robinson, L.
    Karunajeewa, H.
    Abel, H.
    Pulai, K.
    Sanz, S.
    Manning, L.
    Moore, Brioni
    Bassat, Q.
    Mitjà, O.
    Date
    2018
    Type
    Journal Article
    
    Metadata
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    Citation
    Millat-Martínez, P. and Ila, R. and Laman, M. and Robinson, L. and Karunajeewa, H. and Abel, H. and Pulai, K. et al. 2018. Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration. Antimicrobial Agents and Chemotherapy.
    Source Title
    Antimicrobial Agents and Chemotherapy
    DOI
    10.1128/AAC.01153-18
    ISSN
    1098-6596
    School
    School of Pharmacy and Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/73373
    Collection
    • Curtin Research Publications
    Abstract

    BACKGROUND: Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered as a tool for malaria elimination. As an effective and long-acting antimalarial, Dihydroartemisinin-piperaquine (DHA/PQP) appears suitable as a candidate for MDA. However, absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA. METHODS: We conducted an interventional study in Lihir Island, Papua New Guinea, with healthy individuals aged 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 pre-dose and 4h after the final dose of each month. The primary safety endpoint was QTc (using Fridericia's correction; QTcF) prolongation from baseline to 4h post-dosing. We compared the difference in prolongation between the third course post-dose and the first course post-dose. RESULTS: Of 84 enrolled participants, 69 (82%) completed all treatment courses and ECG measurements. The average increase in QTcF was 19.6 ms (SD 17.8) and 17.1 ms (SD 17.1) for the first-course and third-course post-dosing ECGs [risk difference -2.4 (95%CI - 6.9 to 2.1), p=0.285], respectively. We recorded QTcF prolongation >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 >500 ms at any time point. CONCLUSIONS: Three consecutive monthly courses of DHA/PQP were as safe as a single course. The absence of cumulative cardiotoxicity with repeated dosing support the use of monthly DHA/PQP as part of malaria elimination strategies.

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