Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon.
Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon.
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DOI：
10.1093/cid/cix1122
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发表时间：
2018-06-01
期刊：
影响因子：
--
通讯作者：
Kremsner PG
中科院分区：
文献类型：
--
作者：
Mombo-Ngoma G;Remppis J;Sievers M;Zoleko Manego R;Endamne L;Kabwende L;Veletzky L;Nguyen TT;Groger M;Lötsch F;Mischlinger J;Flohr L;Kim J;Cattaneo C;Hutchinson D;Duparc S;Moehrle J;Velavan TP;Lell B;Ramharter M;Adegnika AA;Mordmüller B;Kremsner PG
正在开发以氟米多霉素-哌喹为基础的非青蒿素联合疗法，以应对新出现的青蒿素耐药性的挑战。尽管观察到心电图随着QT间期延长而发生短暂变化，但联合用药似乎具有高效率、安全性和良好的耐受性。正在开发以氟米多霉素-哌喹为基础的非青蒿素联合疗法，以应对新出现的青蒿素耐药性的挑战。该研究是一项2期、单臂、概念验证研究，目的是研究氟米多霉素-哌喹治疗加蓬单一恶性疟原虫感染的疗效、耐受性和安全性。初始寄生虫计数在1000 ~ 150000/µL之间的男女成人和儿童分别口服福米霉素（每日2次，剂量为30mg /kg）和哌喹（每日1次，剂量为16mg /kg），疗程3天，随访63天。主要疗效终点是按方案聚合酶链反应（PCR）校正的第28天足够的临床和寄生虫学反应（ACPR）。100名患者入组。pcr校正的第28天ACPR率为83/83，即100%（95%置信区间为96-100）。14例患者在第28 ~ 63天出现无性寄生虫血症；均经PCR分型为新发感染。福斯米霉素-哌喹治疗导致寄生虫快速清除（中位数，36小时；四分位数间距[IQR]， 6-60）和发热清除时间（中位数，12小时；IQR, 6-48）。心电图评估显示2例患者在服用研究药物后QT间期延长至50 ~ 500 msec。大多数不良事件影响胃肠道和呼吸道，并且是短暂的，严重程度为轻至中度。这是首次报道使用氟米多霉素-哌喹联合用药。尽管观察到心电图随着QT间期延长而发生短暂变化，但联合用药似乎具有高效率、安全性和良好的耐受性。临床试验注册，NCT02198807。
Fosmidomycin–piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval. Fosmidomycin–piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. The study was a phase 2, single-arm, proof-of-concept study of the efficacy, tolerability, and safety of fosmidomycin–piperaquine for the treatment of uncomplicated Plasmodium falciparum monoinfection in Gabon. Adults and children of both sexes with initial parasite counts between 1000 and 150000/µL received oral treatment with fosmidomycin (twice daily doses of 30 mg/kg) and piperaquine (once daily dose of 16 mg/kg) for 3 days and followed-up for 63 days. The primary efficacy endpoint was the per-protocol polymerase chain reaction (PCR)–corrected day 28 adequate clinical and parasitological response (ACPR). One hundred patients were enrolled. The PCR-corrected day 28 ACPR rate was 83/83, or 100% (95% confidence interval, 96–100). Fourteen patients had asexual parasitaemia between day 28 and day 63; all were typed by PCR as new infections. Fosmidomycin–piperaquine therapy led to rapid parasite clearance (median, 36 hours; interquartile range [IQR], 6–60) and fever clearance time (median, 12 hours; IQR, 6–48). The electrocardiogram assessments showed 2 patients with prolonged QT interval >500 msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. This is the first report of the use of the combination fosmidomycin–piperaquine. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval. Clinical Trials Registration. NCT02198807.
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影响因子：
6.4
作者：
Guggisberg, Ann M.;Sundararaman, Sesh A.;Odom, Audrey R.
通讯作者：
Odom, Audrey R.
影响因子：
0.7
作者：
Van Ha, N;Dao, LD;Rabinovich, SA
通讯作者：
Rabinovich, SA
影响因子：
4.5
作者：
Manego, R. Zoleko;Mombo-Ngoma, G.;Matsiegui, P. B.
通讯作者：
Matsiegui, P. B.
影响因子：
3
作者：
Liljander, Anne;Wiklund, Lisa;Farnert, Anna
通讯作者：
Farnert, Anna
影响因子：
4.9
作者：
Vanachayangkul, Pattaraporn;Lon, Chanthap;Saunders, David
通讯作者：
Saunders, David