Department of Neonatalogy, Nantes University Hospital, Nantes, France; Centre d'Investigation Clinique CIC1413, INSERM-Nantes University Hospital, Nantes, France.
Neonatal Medicine, Montpellier University Hospital, Montpellier, France.
J Pediatr. 2021 Jun;233:33-42.e2. doi: 10.1016/j.jpeds.2020.12.008. Epub 2020 Dec 9.
To examine the effects of early echocardiography-targeted ibuprofen treatment of large patent ductus arteriosus (PDA) on survival without cerebral palsy at 24 months of corrected age.
We enrolled infants born at <28 weeks of gestation with a large PDA on echocardiography at 6-12 hours after birth to ibuprofen or placebo by 12 hours of age in a multicenter, double blind, randomized-controlled trial. Open-label ibuprofen was allowed for prespecified criteria of a hemodynamically significant PDA. The primary outcome was survival without cerebral palsy at 24 months of corrected age.
Among 337 enrolled infants, 109 had a small or closed ductus and constituted a reference group; 228 had a large PDA and were randomized. The primary outcome was assessed at 2 years in 108 of 114 (94.7%) and 102 of 114 (89.5%) patients allocated to ibuprofen or placebo, respectively. Survival without cerebral palsy occurred in 77 of 108 (71.3%) after ibuprofen, 73 of 102 (71.6%) after placebo (adjusted relative risk 0.98, 95% CI 0.83-1.16, P = .83), and 77 of 101 (76.2%) in reference group. Infants treated with ibuprofen had a lower incidence of PDA at day 3. Severe pulmonary hemorrhage during the first 3 days occurred in 2 of 114 (1.8%) infants treated with ibuprofen and 9 of 114 (7.9%) infants treated with placebo (adjusted relative risk 0.22, 95% CI 0.05-1.00, P = .05). Open-label rescue treatment with ibuprofen occurred in 62.3% of infants treated with placebo and 17.5% of infants treated with ibuprofen (P < .001), at a median (IQR) age of 4 (3, 5) and 4 (4, 12) days, respectively.
Early echocardiography-targeted ibuprofen treatment of a large PDA did not change the rate of survival without cerebral palsy.
Eudract 2011-003063-30 and ClinicalTrials.gov: NCT01630278.
研究生后 6-12 小时内给予布洛芬或安慰剂治疗早产儿大动脉导管未闭（PDA）对 24 月龄时无脑瘫生存率的影响。
我们纳入了胎龄<28 周且生后 6-12 小时心脏超声显示存在大 PDA 的婴儿，在 12 小时内通过多中心、双盲、随机对照试验给予布洛芬或安慰剂。对于存在血流动力学意义的大 PDA 的患儿，可开放标签给予布洛芬。主要结局是校正胎龄 24 月龄时无脑瘫生存率。
337 名纳入患儿中，109 例为小或闭合导管，构成参照组；228 例存在大 PDA 并随机分组。114 例患儿中，108 例（94.7%）和 114 例患儿中的 102 例（89.5%）分别于 2 年时评估了主要结局。108 例患儿中有 77 例（71.3%）接受布洛芬治疗，102 例患儿中有 73 例（71.6%）接受安慰剂治疗（校正相对风险 0.98，95%CI 0.83-1.16，P=0.83），101 例参照组患儿中有 77 例（76.2%）。接受布洛芬治疗的患儿 PDA 在第 3 天的发生率较低。接受布洛芬治疗的患儿中有 2 例（1.8%）和接受安慰剂治疗的患儿中有 9 例（7.9%）在生后第 1-3 天发生严重肺出血（校正相对风险 0.22，95%CI 0.05-1.00，P=0.05）。接受安慰剂治疗的患儿中有 62.3%（69/111）和接受布洛芬治疗的患儿中有 17.5%（20/114）需要开放标签给予布洛芬进行挽救治疗（P<0.001），中位（IQR）年龄分别为 4（3，5）和 4（4，12）天。
早期心脏超声靶向给予布洛芬治疗大 PDA 并不能改变无脑瘫生存率。
Eudract 2011-003063-30 和 ClinicalTrials.gov：NCT01630278。
