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

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 cardi...

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Autores: Millat Martínez, Pere, Ila, Rhoda, Laman, Moses, Robinson, Leanne J., Karunajeewa, Harin, Abel, Haina, Pulai, Kevin, Sanz, Sergi, Manning, Laurens, Moore, Brioni R., Bassat Orellana, Quique, Mitjà Villar, Oriol
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2018
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/128526
Acesso em linha:https://hdl.handle.net/2445/128526
Access Level:Acceso aberto
Palavra-chave:Electrocardiografia
Malària
Electrocardiography
Malaria
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spelling Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug AdministrationMillat Martínez, PereIla, RhodaLaman, MosesRobinson, Leanne J.Karunajeewa, HarinAbel, HainaPulai, KevinSanz, SergiManning, LaurensMoore, Brioni R.Bassat Orellana, QuiqueMitjà Villar, OriolElectrocardiografiaMalàriaElectrocardiographyMalariaMass 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.American Society for Microbiology2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/128526Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1128/AAC.01153-18Antimicrobial Agents and Chemotherapy, 2018, vol. 62http://dx.doi.org/ 10.1128/AAC.01153-18(c) American Society for Microbiology, 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1285262026-05-27T06:46:51Z
dc.title.none.fl_str_mv 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
spellingShingle Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration
Millat Martínez, Pere
Electrocardiografia
Malària
Electrocardiography
Malaria
title_short 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_sort Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration
dc.creator.none.fl_str_mv Millat Martínez, Pere
Ila, Rhoda
Laman, Moses
Robinson, Leanne J.
Karunajeewa, Harin
Abel, Haina
Pulai, Kevin
Sanz, Sergi
Manning, Laurens
Moore, Brioni R.
Bassat Orellana, Quique
Mitjà Villar, Oriol
author Millat Martínez, Pere
author_facet Millat Martínez, Pere
Ila, Rhoda
Laman, Moses
Robinson, Leanne J.
Karunajeewa, Harin
Abel, Haina
Pulai, Kevin
Sanz, Sergi
Manning, Laurens
Moore, Brioni R.
Bassat Orellana, Quique
Mitjà Villar, Oriol
author_role author
author2 Ila, Rhoda
Laman, Moses
Robinson, Leanne J.
Karunajeewa, Harin
Abel, Haina
Pulai, Kevin
Sanz, Sergi
Manning, Laurens
Moore, Brioni R.
Bassat Orellana, Quique
Mitjà Villar, Oriol
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Electrocardiografia
Malària
Electrocardiography
Malaria
topic Electrocardiografia
Malària
Electrocardiography
Malaria
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/128526
url https://hdl.handle.net/2445/128526
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1128/AAC.01153-18
Antimicrobial Agents and Chemotherapy, 2018, vol. 62
http://dx.doi.org/ 10.1128/AAC.01153-18
dc.rights.none.fl_str_mv (c) American Society for Microbiology, 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Microbiology, 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv Articles publicats en revistes (ISGlobal)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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