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.
Centre D'Investigation Clinique Antilles-Guyane, Inserm 1424, Centre Hospitalier de Cayenne, Cayenne, France.
Malar J. 2021 May 8;20(1):214. doi: 10.1186/s12936-021-03750-x.
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.
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.
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/m (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%).
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.
前往流行地区的欧洲旅行者有患疟疾的风险，并且可能患有与流行地区本地人不同的一系列合并症。由于缺乏该人群的纵向研究， Artesunate（二氢青蒿素）-Piperaquine（APQ） Eurartesim 在治疗无并发症的恶性疟原虫疟疾时的安全性概况，特别是心脏问题，尚未得到充分描述。本研究旨在部分填补这一空白。
参与者通过 6 个欧洲国家的 15 个中心的医疗保健提供者安全注册系统在 2013 年至 2016 年期间招募。收集不良事件（AE），特别关注心血管安全性，包括在基线和治疗后使用 Bazett （QTcB）或 Fridericia（QTcF）方法校正后的心电图 QT 间隔，以评估 QTcB 和/或 QTcF 延长。将男性和儿童的 QTcB 值> 450ms 和女性的 QTcB 值> 470ms 定义为延长。
在 294 名参与者中，30.3%为女性，13.7%为白种人，13.5%为当前吸烟者，13.6%为当前饮酒者，42.2%有至少一种病史。平均（SD）年龄和体重指数分别为 39.8 岁（13.2）和 25.9kg/m（4.7）。其中，75 人共报告了 129 起 AE（27 例严重），46 起被怀疑与 APQ 有关（11 例严重），主要与血液、胃肠道或感染有关。女性和非非洲参与者的 AE 明显（p<0.05）更多。在 AE 中，21 起因心脏毒性（7.1%），主要为 QT 延长，6 起因神经毒性（2.0%），主要为头晕。使用 QTcF 校正后，17/143 名参与者（11.9%）出现 QT 延长，其中仅 2 名报告 QTcF>500ms（毫秒），但无临床症状。使用 QTcB 校正后，9 名参与者（6.3%）的>60ms 增加。在 65 岁以上的参与者中观察到延长趋势，但该组仅有少数参与者。未报告新的安全信号。总有效率为 255/257（99.2%）。
APQ 似乎是一种有效且耐受性良好的药物，可用于治疗在欧洲国家招募的疟疾患者。AE 和 QT 延长在来自流行地区的更大队列中获得的范围内。试验注册 本研究已在欧盟事后授权研究登记处注册为 EUPAS6942。
