Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used “off label” in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis. We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12–47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters. The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group. ClinicalTrials.gov NCT03640377 . Registered on 21 Aug 2018.

中文翻译：

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学龄前儿童中的吡喹酮 (PIP) 试验：针对 4 岁以下儿童进行的 II 期 PK/PD 驱动的吡喹酮随机对照试验的研究方案

全世界有超过 2 亿人感染了血吸虫，其中一半以上的感染发生在儿童身上。许多儿童在生命早期经历过第一次感染，这会影响他们的成长和发育；然而，吡喹酮 (PZQ) 是一种在全球范围内用于治疗血吸虫病的药物，仅在成人和 4 岁以上儿童中获得监管批准，尽管它经常在地方病环境中“超说明书”使用。此外，药代动力学/药效学 (PK/PD) 证据表明 40 mg/kg 的标准 PZQ 剂量不足以用于学龄前儿童 (PSAC)。我们的目标是了解优化 PSAC 与肠道血吸虫病治疗的最佳方法。我们将进行随机化，在乌干达的曼氏血吸虫流行区和菲律宾的日本血吸虫流行区进行的 II 期对照试验。六百名儿童，每个环境 300 名，12-47 个月的血吸虫感染儿童将以 1：1：1：1 的比例随机接受（1）基线时 40 mg / kg PZQ 和 6 个月时安慰剂，（ 2) 基线时 40 mg/kg PZQ 和 6 个月时 40 mg/kg PZQ，(3) 基线时 80 mg/kg PZQ 和 6 个月时安慰剂，或 (4) 基线时 80 mg/kg PZQ 和 80 mg/ 6 个月时公斤 PZQ。基线治疗后，将对儿童进行为期 12 个月的随访。共同主要结果将是 4 周时的治愈率和卵子减少率。次要结果包括 4 周时通过新抗原终点评估的药物疗效、积极收集的不良事件和治疗后 12 小时的毒性，6 个月和 12 个月时的发病率和营养结果、炎症和环境性肠病的生物标志物以及 PZQ PK/PD 参数。该试验将提供有价值的信息，说明 80 mg/kg PZQ 剂量在 PSAC 中的安全性和有效性，以及在这个弱势年龄组中每六个月治疗与每年治疗的影响。临床试验网站 NCT03640377。2018 年 8 月 21 日注册。