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

Authors
  • Vignier, Nicolas1, 2, 3
  • Bouchaud, Olivier1, 4
  • Angheben, Andrea4, 5
  • Bottieau, Emmanuel4, 6
  • Calleri, Guido7
  • Salas-Coronas, Joaquín4, 8
  • Martin, Charlotte9
  • Ramos, José Manuel10
  • Mechain, Matthieu11
  • Rapp, Christophe12
  • Nothdurft, Hans-Dieter13
  • Velasco, Maria14
  • Bardají, Azucena4, 15, 16, 17
  • Rojo-Marcos, Gerardo18
  • Visser, Leo G.4, 19
  • Hatz, Christoph4, 20, 21
  • Bisoffi, Zeno4, 5
  • Jelinek, Tomas4, 22
  • Duparc, Stephan23
  • Bourhis, Yann24
  • And 6 more
  • 1 Sorbonne Paris Nord University, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Bobigny, France , Bobigny (France)
  • 2 Centre Hospitalier de Cayenne, Cayenne, France , Cayenne (France)
  • 3 Sorbonne Université, Institut Pierre Louis D’Épidémiologie et de Santé Publique IPLESP, Paris, France , Paris (France)
  • 4 TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy , Verona (Italy)
  • 5 IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy , Negrar (Italy)
  • 6 Institute of Tropical Medicine, Antwerp, Belgium , Antwerp (Belgium)
  • 7 Azienda Sanitaria Locale “Cità Di Torino”, Torino, Italy , Torino (Italy)
  • 8 Hospital de Poniente, El Ejido, Almería, Spain , El Ejido (Spain)
  • 9 Travel Clinic, CHU St Pierre, Brussels, Belgium , Brussels (Belgium)
  • 10 Hospital General Universitario Alicante, Alicante, Spain , Alicante (Spain)
  • 11 Hôpital St André, Bordeaux, France , Bordeaux (France)
  • 12 Hôpital D’Instruction Des Armées Begin, Saint Mandé, France , Saint Mandé (France)
  • 13 Klinikum Der LMU München, Munich, Germany , Munich (Germany)
  • 14 Hospital Universitario Fundación Alcorcón, Madrid, Spain , Madrid (Spain)
  • 15 ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain , Barcelona (Spain)
  • 16 Centro de Investigação Em Saúde de Manhiça, Maputo, Mozambique , Maputo (Mozambique)
  • 17 Consorcio de Investigación Biomédica en Red de Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain , Madrid (Spain)
  • 18 Hospital Universitario Príncipe de Asturias, Alcalà de Henares, Madrid, Spain , Alcalà de Henares, Madrid (Spain)
  • 19 Leiden University Medical Centre, Leiden, Netherlands , Leiden (Netherlands)
  • 20 Swiss Tropical and Public Health Institute, Basel, Switzerland , Basel (Switzerland)
  • 21 University of Basel, Basel, Switzerland , Basel (Switzerland)
  • 22 Berliner Centrum Fürr Reise- Und Tropenmedizin, Berlin, Germany , Berlin (Germany)
  • 23 Medicines for Malaria Venture, Geneva, Switzerland , Geneva (Switzerland)
  • 24 Mapi Group, Real World Evidence, Lyon, France , Lyon (France)
  • 25 Alfasigma S.P.A, Bologna, Italy , Bologna (Italy)
  • 26 London School of Hygiene and Tropical Medicine, London, UK , London (United Kingdom)
Type
Published Article
Journal
Malaria Journal
Publisher
Springer (Biomed Central Ltd.)
Publication Date
May 08, 2021
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12936-021-03750-x
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundEuropean 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.MethodsParticipants 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.ResultsAmong 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%).ConclusionsAPQ 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

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