Longitudinal study based on a safety registry for malaria patients treated with artenimol-piperaquine in six European countries

Nicolas Vignier, Olivier Bouchaud, Andrea Angheben, Emmanuel Bottieau, Guido Calleri, Joaquín Salas-Coronas, Charlotte Martin, José Manuel Ramos, Matthieu Mechain, Christophe Rapp, Hans-Dieter Nothdurft, Maria Velasco, Azucena Bardají, Gerardo Rojo-Marcos, Leo G Visser, Christoph Hatz, Zeno Bisoffi, Tomas Jelinek, Stephan Duparc, Yann BourhisSilva Tommasini, Maurizio Iannucelli, Antonella Bacchieri, Giovan Giuseppe Mattera, Emilio Merlo Pich, Ronald H Behrens

Research output: Contribution to journalA1: Web of Science-articlepeer-review

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BACKGROUND: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)-piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap.

METHODS: Participants were recruited through Health Care Provider's safety registry in 15 centres across 6 European countries in the period 2013-2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett's (QTcB) or Fridericia's (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females.

RESULTS: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%).

CONCLUSIONS: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942.

Original languageEnglish
Article number214
JournalMalaria Journal
Issue number1
Number of pages14
Publication statusPublished - 2021


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