University Hospital of North Tees, Hardwick Road, Stockton-On-Tees, TS19 8PE, UK.
National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Headington, Oxford, OX3 7LF, UK.
BMC Pediatr. 2021 Feb 26;21(1):100. doi: 10.1186/s12887-021-02558-7.
The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic.
This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23-28 weeks' gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23-28 weeks' gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks' postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age.
Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks' postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age.
ISRCTN84264977 . Date assigned: 15/09/2010.
是否早期治疗动脉导管未闭（PDA）或等待症状出现，这一问题在新生儿医学的研究议程上仍处于高位。在英国，每年约有 7000 名 29 周以下的极早产儿出生。在 40%的情况下，即使到 4 个月大，PDA 仍不会自然闭合。未经治疗的 PDA 可能与一些严重的、危及生命的短期和长期并发症有关。需要可靠的数据来支持关于 PDA 治疗的临床决策，以预防高危婴儿出现严重并发症，同时尽量减少婴儿的不必要暴露。随着常规床边超声心动图的应用，即使在有症状之前，患有大 PDA 的婴儿也可以得到诊断。
这是一项多中心、盲法、随机、安慰剂对照的平行组试验，旨在确定在 23-28 周胎龄的极早产儿中，用静脉注射布洛芬早期靶向治疗大 PDA 是否能改善短期和长期的健康和经济结局。在获得父母知情同意的情况下，通过超声心动图对入住三级新生儿病房的极早产儿进行筛查。超声心动图显示存在大 PDA（直径至少 1.5 毫米且 PDA 搏动性无限制）的婴儿在出生后 72 小时内随机分配至布洛芬组或安慰剂组。主要终点是在出生后 36 周的经校正的孕龄时死亡或出现中度或重度支气管肺发育不良（BPD）的复合结局。
预防性药物治疗会使所有早产儿不必要地暴露于药物治疗的潜在严重副作用之下，而此时他们的 PDA 可能已经自然闭合。然而，等到婴儿出现症状再进行治疗，可能会因已经发生不可逆转的损害而失去治疗效果。对无症状婴儿进行有针对性的早期药物治疗 PDA 可能会克服预防性（过度治疗）和症状性（可能为时已晚）方法的缺点。这可能会改善在出生后 36 周经校正的孕龄时临床上重要的短期临床（死亡率和中度或重度 BPD）和长期健康结局（中度或重度神经发育障碍和呼吸道发病率）。
ISRCTN84264977。日期分配：2010 年 9 月 15 日。
