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

Malaria Journal

Guido Calleri¹  José Manuel Ramos²  Nicolas Vignier³  Olivier Bouchaud⁴  Maria Velasco⁵  Gerardo Rojo-Marcos⁶  Christophe Rapp⁷  Matthieu Mechain⁸  Hans-Dieter Nothdurft⁹  Yann Bourhis^1,10  Stephan Duparc^1,11  Emilio Merlo Pich^1,12  Antonella Bacchieri^1,12  Maurizio Iannucelli^1,12  Giovan Giuseppe Mattera^1,12  Silva Tommasini^1,12  Charlotte Martin^1,13  Tomas Jelinek^1,14  Ronald H. Behrens^1,15  Leo G. Visser^1,16  Zeno Bisoffi^1,17  Andrea Angheben^1,17  Azucena Bardají^1,18  Emmanuel Bottieau^1,19  Christoph Hatz^2,20  Joaquín Salas-Coronas^2,21 

[1]Azienda Sanitaria Locale “Cità Di Torino”, Torino, Italy

[2]Consulta de Enfermedades Importadas Y Parasitología Clínica, Unidad de Enfermedades Infecciosas, Hospital General Universitario Alicante, Alicante, Spain

[3]Department of Infectious and Tropical Diseases, and Laboratoire Éducations et Pratiques de Santé (LEPS EA 3412), Sorbonne Paris Nord University, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Bobigny, France

[4]Centre D’Investigation Clinique Antilles-Guyane, Inserm 1424, Centre Hospitalier de Cayenne, Cayenne, France

[5]INSERM, Sorbonne Université, Institut Pierre Louis D’Épidémiologie et de Santé Publique IPLESP, Paris, France

[6]Department of Infectious and Tropical Diseases, and Laboratoire Éducations et Pratiques de Santé (LEPS EA 3412), Sorbonne Paris Nord University, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Bobigny, France

[7]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[8]Hospital Universitario Fundación Alcorcón, Madrid, Spain

[9]Hospital Universitario Príncipe de Asturias, Alcalà de Henares, Madrid, Spain

[10]Hôpital D’Instruction Des Armées Begin, Saint Mandé, France

[11]Hôpital St André, Bordeaux, France

[12]Klinikum Der LMU München, Munich, Germany

[13]Mapi Group, Real World Evidence, Lyon, France

[14]Medicines for Malaria Venture, Geneva, Switzerland

[15]Research & Development, Alfasigma S.P.A, Bologna, Italy

[16]Travel Clinic, CHU St Pierre, Brussels, Belgium

[17]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[18]Berliner Centrum Fürr Reise- Und Tropenmedizin, Berlin, Germany

[19]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[20]Clinical Research Dept, Faculty of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

[21]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[22]Department of Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands

[23]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[24]Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy

[25]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[26]ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

[27]Centro de Investigação Em Saúde de Manhiça, Maputo, Mozambique

[28]Consorcio de Investigación Biomédica en Red de Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain

[29]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[30]Institute of Tropical Medicine, Antwerp, Belgium

[31]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[32]Swiss Tropical and Public Health Institute, Basel, Switzerland

[33]University of Basel, Basel, Switzerland

[34]TropNet, A European Network for Tropical and Travel Medicine, Verona, Italy

[35]Tropical Medicine Unit, Hospital de Poniente, El Ejido, Almería, Spain

关键词: Imported malaria;    Artenimol;    Piperaquine;    Eurartesim;    QTc prolongation;    Safety;    Adverse events;    Artemisinin;    Plasmodium falciparum;   

DOI  :  10.1186/s12936-021-03750-x

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY