Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM, INRA, F-75004, Paris, France.
Unit of Population Epidemiology, Department of Primary Care Medicine, Geneva University Hospitals, 1205, Geneva, Switzerland.
BMC Pregnancy Childbirth. 2021 Sep 8;21(1):614. doi: 10.1186/s12884-021-04047-2.
Preterm prelabor rupture of membranes (PPROM) before 34 weeks of gestation complicates 1% of pregnancies and accounts for one-third of preterm births. International guidelines recommend expectant management, along with antenatal steroids before 34 weeks and antibiotics. Up-to-date evidence about the risks and benefits of administering tocolysis after PPROM, however, is lacking. In theory, reducing uterine contractility could delay delivery and reduce the risks of prematurity and its adverse short- and long-term consequences, but it might also prolong fetal exposure to inflammation, infection, and acute obstetric complications, potentially associated with neonatal death or long-term sequelae. The primary objective of this study is to assess whether short-term (48 h) tocolysis reduces perinatal mortality/morbidity in PPROM at 22 to 33 completed weeks of gestation.
A randomized, double-blind, placebo-controlled, superiority trial will be performed in 29 French maternity units. Women with PPROM between 22 and 33 weeks of gestation, a singleton pregnancy, and no condition contraindicating expectant management will be randomized to receive a 48-hour oral treatment by either nifedipine or placebo (1:1 ratio). The primary outcome will be the occurrence of perinatal mortality/morbidity, a composite outcome including fetal death, neonatal death, or severe neonatal morbidity before discharge. If we assume an alpha-risk of 0.05 and beta-risk of 0.20 (i.e., a statistical power of 80%), 702 women (351 per arm) are required to show a reduction of the primary endpoint from 35% (placebo group) to 25% (nifedipine group). We plan to increase the required number of subjects by 20%, to replace any patients who leave the study early. The total number of subjects required is thus 850. Data will be analyzed by the intention-to-treat principle.
This trial will inform practices and policies worldwide. Optimized prenatal management to improve the prognosis of infants born preterm could benefit about 50,000 women in the European Union and 40,000 in the United States each year.
ClinicalTrials.gov identifier: NCT03976063 (registration date June 5, 2019).
早产胎膜早破（PPROM）在妊娠 34 周前发生，占所有早产的 1%。国际指南建议期待治疗，并在妊娠 34 周前给予产前类固醇和抗生素。然而，目前尚无关于 PPROM 后使用保胎治疗的风险和益处的最新证据。理论上，降低子宫收缩力可以延迟分娩，降低早产及其不良短期和长期后果的风险，但也可能延长胎儿暴露于炎症、感染和急性产科并发症的时间，这可能与新生儿死亡或长期后遗症有关。本研究的主要目的是评估 22 至 33 周妊娠时，短期（48 小时）保胎治疗是否能降低 PPROM 的围产儿死亡率/发病率。
将在 29 家法国产科单位进行一项随机、双盲、安慰剂对照、优效性试验。22 至 33 周妊娠、单胎妊娠且无期待治疗禁忌证的孕妇将被随机分配接受 48 小时口服硝苯地平或安慰剂（1:1 比例）治疗。主要结局是围产儿死亡率/发病率的发生，这是一个复合结局，包括胎儿死亡、新生儿死亡或出院前严重新生儿发病率。如果我们假设α风险为 0.05，β风险为 0.20（即统计效能为 80%），则需要 702 名女性（每组 351 名）来显示主要终点从 35%（安慰剂组）降低到 25%（硝苯地平组）。我们计划增加 20%的所需受试者数量，以替换任何提前退出研究的患者。因此，所需的受试者总数为 850 名。数据将根据意向治疗原则进行分析。
这项试验将为全球的实践和政策提供信息。优化产前管理以改善早产儿的预后，每年可使欧盟约 5 万名和美国约 4 万名妇女受益。
ClinicalTrials.gov 标识符：NCT03976063（注册日期为 2019 年 6 月 5 日）。
