Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome. In most preterm infants, a PDA will eventually close spontaneously, hence PDA treatment potentially increases the risk of iatrogenic adverse effects. Therefore, expectant management is gaining interest, even in the absence of convincing evidence to support this strategy. The BeNeDuctus trial is a multicentre, randomised, non-inferiority trial assessing early pharmacological treatment (24–72 h postnatal age) with ibuprofen versus expectant management of PDA in preterm infants in Europe. Preterm infants with a gestational age of less than 28 weeks and an echocardiographic-confirmed PDA with a transductal diameter of > 1.5 mm are randomly allocated to early pharmacological treatment with ibuprofen or expectant management after parental informed consent. The primary outcome measure is the composite outcome of mortality, and/or necrotizing enterocolitis Bell stage ≥ IIa, and/or bronchopulmonary dysplasia, all established at a postmenstrual age of 36 weeks. Secondary short-term outcomes are comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. This statistical analysis plan focusses on the short-term outcome and is written and submitted without knowledge of the data. ClinicalTrials.gov NTR5479. Registered on October 19, 2015, with the Dutch Trial Registry, sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28.

中文翻译：

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早产儿动脉导管未闭早期治疗与期待治疗的多中心、随机非劣效性试验（BeNeDuctus 试验）：统计分析计划

关于早产儿动脉导管未闭 (PDA) 的最佳管理存在争议。持续性 PDA 与新生儿死亡率和发病率有关，但因果关系仍未得到证实。尽管药物和/或手术治疗对 PDA 闭合有效，但这并没有改善新生儿的结局。在大多数早产儿中，PDA 最终会自行关闭，因此 PDA 治疗可能会增加医源性不良反应的风险。因此，即使在没有令人信服的证据支持这一策略的情况下，期待治疗也引起了人们的兴趣。BeNeDuctus 试验是一项多中心、随机、非劣效性试验，评估欧洲早产儿使用布洛芬与期待治疗 PDA 的早期药物治疗（出生后 24-72 小时）。胎龄小于 28 周且经超声心动图证实的 PDA 转导管直径 > 1.5 mm 的早产儿在父母知情同意后随机分配接受布洛芬早期药物治疗或期待治疗。主要结局指标是死亡率、和/或坏死性小肠结肠炎 Bell 分期 ≥ IIa 和/或支气管肺发育不良的复合结局，所有这些结局均在 36 周的经后年龄确定。次要短期结果是住院期间评估的合并症和不良事件，以及在 2 岁矫正年龄评估的长期神经发育结果。该统计分析计划侧重于短期结果，是在不了解数据的情况下编写和提交的。ClinicalTrials.gov NTR5479。2015年10月19日注册，