Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia.
Tropical Diseases Research Centre, Ndola, Zambia.
Clin Infect Dis. 2022 Jan 29;74(2):180-188. doi: 10.1093/cid/ciab425.
Pyronaridine-artesunate (PA) is a registered artemisinin-based combination therapy, potentially useful for mass drug administration campaigns. However, further data are needed to evaluate its efficacy, safety and tolerability as full or incomplete treatment in asymptomatic Plasmodium falciparum-infected individuals.
This phase II, multi-center, open label, randomized clinical trial was conducted in The Gambia and Zambia. Participants with microscopically confirmed asymptomatic P. falciparum infection were randomly assigned (1:1:1) to receive a 3-day, 2-day, or 1-day treatment regimen of PA (180:60 mg), dosed according to bodyweight. The primary efficacy outcome was polymerase chain reaction (PCR)-adjusted adequate parasitological response (APR) at day 28 in the per-protocol population.
A total of 303 participants were randomized. Day 28 PCR-adjusted APR was 100% for both the 3-day (98/98) and 2-day regimens (96/96), and 96.8% (89/94) for the 1-day regimen. Efficacy was maintained at 100% until day 63 for the 3-day and 2-day regimens but declined to 94.4% (84/89) with the 1-day regimen. Adverse event frequency was similar between the 3-day (51.5% [52/101]), 2-day (52.5% [52/99]), and 1-day (54.4% [56/103]) regimens; the majority of adverse events were of grade 1 or 2 severity (85% [136/160]). Asymptomatic, transient increases (>3 times the upper limit of normal) in alanine aminotransferase/aspartate aminotransferase were observed for 6/301 (2.0%) participants.
PA had high efficacy and good tolerability in asymptomatic P. falciparum-infected individuals, with similar efficacy for the full 3-day and incomplete 2-day regimens. Although good adherence to the 3-day regimen should be encouraged, these results support the further investigation of PA for mass drug administration campaigns.
NCT03814616.
派隆那林-青蒿琥酯（PA）是一种已注册的青蒿素类复方疗法，有可能用于大规模药物治疗活动。然而，需要进一步的数据来评估其在无症状感染疟原虫恶性疟患者中作为全疗程或不完整疗程的疗效、安全性和耐受性。
这是一项在冈比亚和赞比亚进行的 II 期、多中心、开放性标签、随机临床试验。参与者经显微镜确认患有无症状感染疟原虫恶性疟，随机（1:1:1）接受 3 天、2 天或 1 天疗程的 PA（180:60mg）治疗，根据体重给药。主要疗效终点是方案人群中第 28 天聚合酶链反应（PCR）校正的充分寄生虫学应答（APR）。
共纳入 303 名参与者。3 天和 2 天疗程的第 28 天 PCR 校正 APR 均为 100%（98/98），1 天疗程为 96.8%（89/94）。3 天和 2 天疗程的疗效持续至第 63 天，1 天疗程的疗效下降至 94.4%（84/89）。3 天（51.5%[52/101]）、2 天（52.5%[52/99]）和 1 天（54.4%[56/103]）疗程的不良反应频率相似；大多数不良反应为 1 级或 2 级（85%[136/160]）。6/301（2.0%）名参与者出现无症状、短暂性（超过正常值上限 3 倍以上）的丙氨酸氨基转移酶/天冬氨酸氨基转移酶升高。
PA 对无症状感染疟原虫恶性疟患者具有高疗效和良好的耐受性，全疗程 3 天和不完整疗程 2 天的疗效相似。虽然应鼓励良好的依从性 3 天疗程，但这些结果支持进一步研究 PA 用于大规模药物治疗活动。
NCT03814616。
