National Malaria Center, Phnom Penh, Cambodia.
PLoS One. 2011 Jan 18;6(1):e14501. doi: 10.1371/journal.pone.0014501.
New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria.
This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection were randomized (1:1) to receive pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; p<0.0001), as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate.
Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug.
Clinicaltrials.gov NCT00440999.
需要新的抗疟药物来治疗间日疟原虫和恶性疟原虫疟疾。本研究比较了派隆那林-青蒿琥酯与氯喹治疗无并发症间日疟原虫疟疾的疗效和安全性。
这是一项在柬埔寨、泰国、印度和印度尼西亚的五个中心进行的 III 期随机、双盲、非劣效性试验。采用双盲设计，对经显微镜确认的间日疟原虫单感染患者（年龄>3-≤60 岁）进行随机分组（1:1），分别接受派隆那林-青蒿琥酯（目标剂量 7.2:2.4mg/kg 至 13.8:4.6mg/kg）或氯喹（标准剂量）每日一次，连续三天。每组各有 228 名随机患者。主要终点为第 14 天的治愈率（方案人群），派隆那林-青蒿琥酯为 99.5%（217/218；95%CI 97.5，100），氯喹为 100%（209/209；95%CI 98.3，100）。派隆那林与氯喹相当：治疗差异-0.5%（95%CI-2.6，1.4），即治疗差异的 2 侧 95%CI 的下限大于-10%。派隆那林-青蒿琥酯的治愈率在第 21、28、35 和 42 天与氯喹相当。派隆那林-青蒿琥酯的寄生虫清除时间（中位数 23.0 小时）短于氯喹（32.0 小时；p<0.0001），退热时间（中位数分别为 15.9 小时和 23.8 小时；p=0.0017）也短于氯喹。派隆那林-青蒿琥酯治疗后至第 42 天的恶性疟原虫感染发生率的 Kaplan-Meier 估计值为 2.5%，氯喹为 6.1%（p=0.048，对数秩检验）。第 42 天之前的间日疟原虫或恶性疟原虫感染发生率分别为 6.8%和 12.4%（p=0.022，对数秩检验）。无死亡病例。派隆那林-青蒿琥酯组有 92/228（40.4%）例患者发生不良事件，氯喹组有 72/228（31.6%）例患者发生不良事件。派隆那林-青蒿琥酯组出现轻度和短暂的肝酶升高。
派隆那林-青蒿琥酯治疗急性无并发症间日疟原虫疟疾的疗效至少与氯喹相当。由于派隆那林-青蒿琥酯对恶性疟原虫也有效，因此该联合用药具有作为全球抗疟药物的潜力。
Clinicaltrials.gov NCT00440999。
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