Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration
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 saf...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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American Society for Microbiology
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/73373 |
| _version_ | 1848762997526233088 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Millat-Martínez, P. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:56:27Z |
| format | Journal Article |
| id | curtin-20.500.11937-73373 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:56:27Z |
| publishDate | 2018 |
| publisher | American Society for Microbiology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-733732019-04-09T08:05:20Z Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration 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. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/73373 10.1128/AAC.01153-18 American Society for Microbiology restricted |
| spellingShingle | 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. Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| title | Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| title_full | Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| title_fullStr | Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| title_full_unstemmed | Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| title_short | Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| title_sort | electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration |
| url | http://hdl.handle.net/20.500.11937/73373 |