Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Malar J. 2024 Feb 28;23(1):61. doi: 10.1186/s12936-024-04885-3.
Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine-artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM).
An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether-lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered.
In the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320).
Anti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study. Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876.
儿童特别容易感染疟疾。本分析整合了三项随机临床试验和一项真实世界研究（CANTAM）中吡喹酮-青蒿琥酯（PA）儿科颗粒的临床数据。
对三项随机临床试验中至少接受一剂研究药物的患者（儿科安全性人群）进行个体患者数据的综合安全性分析。PA 每日一次给药 3 天；两项试验包括对照药青蒿琥酯-甲氟喹。评估 PCR 校正第 28 天充分的临床和寄生虫学反应（ACPR）。还考虑了真实世界中 PA 儿科颗粒的安全性和有效性。
在综合安全性分析中，63.9%（95%CI 60.2，67.4；426/667）的患者在接受 PA 后出现不良事件，62.0%（95%CI 56.9，66.9；222/358）的患者在接受 AL 后出现不良事件。PA（7.8%[95%CI 6.0，10.1；52/667]）比 AL（3.4%[95%CI 1.9，5.8；12/358]）更常见呕吐，相对风险为 2.3（95%CI 1.3，4.3；P=0.004），主要发生在第一次 PA 剂量后（6.7%，45/667），不影响再次给药或依从性。PA（3.1%[95%CI 2.1，4.8；21/667]）比 AL（8.1%[95%CI 5.7，11.4；29/358]）更罕见发生 QT 间期延长，相对风险为 0.39（95%CI 0.22，0.67；P=0.0007）。在 CANTAM 中，17.7%（95%CI 16.3，19.2；460/2599）的患者报告了不良事件，最常见的是呕吐（5.4%[95%CI 4.6，6.4；141/2599]），主要发生在第一次剂量后（4.5%，117/2599），所有患者均成功再次给药，发热（5.4%[95%CI 4.6，6.3；140/2599]）。在两项比较性临床试验中，PA 儿科颗粒在方案人群中的第 28 天 ACPR 为 97.1%（95%CI 94.6，98.6；329/339）和 100%（95%CI 99.3，100；514/514），分别与 AL 的 98.8%（95%CI 95.7，99.9；165/167）和 98.4%（95%CI 95.5，99.7；188/191）相比。在 CANTAM 中，PA 的临床疗效为 98.0%（95%CI 97.3，98.5；2273/2320）。
PA 儿科颗粒每日一次给药 3 天治疗抗疟药物在儿童中耐受性良好，在临床试验中显示出良好的临床疗效，在真实世界研究中得到了证实。
Clinicaltrials.gov：SP-C-003-05：标识符 NCT00331136；SP-C-007-07：标识符 NCT0541385；SP-C-021-15：标识符 NCT03201770。泛非临床试验注册中心：SP-C-013-11：标识符 PACTR201105000286876。
