Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol.
Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol.
复制标题
DOI：
10.1136/bmjopen-2015-008211
复制
发表时间：
2015-10-28
期刊：
影响因子：
2.9
通讯作者：
Tong S
中科院分区：
文献类型：
--
作者：
Cluver CA;Walker SP;Mol BW;Theron GB;Hall DR;Hiscock R;Hannan N;Tong S
先兆子痫是妊娠的主要并发症，全球每年造成60，000例孕产妇死亡，以及更多数量的胎儿丢失。 除了分娩，没有明确的治疗方法。一种可以淬灭疾病过程的药物可能有助于治疗早发性先兆子痫，因为它可以使妊娠安全地继续妊娠，胎儿结局显着改善。我们已经产生了临床前数据，以显示埃索美拉唑，质子泵抑制剂用于胃反流，具有强大的生物学效应，使其成为一个值得的治疗候选人。埃索美拉唑有效地降低胎盘和内皮细胞分泌可溶性fms样酪氨酸激酶1（sFlt-1）和可溶性内皮糖蛋白，并具有减轻内皮功能障碍和氧化应激的生物学作用。我们建议进行一项II期、双盲、随机对照临床试验，以检查每天给予40 mg埃索美拉唑是否可以延长早发性先兆子痫妇女的妊娠期。 我们将招募120名妇女（胎龄26+0至31+6周），她们将被随机分配接受埃索美拉唑或相同的安慰剂。 主要结局为从随机化至分娩的天数。次要结局包括母体、胎儿和新生儿复合结局和个体结局。产妇结局包括产妇死亡、子痫、肺水肿、重度肾损害、脑血管事件和肝血肿或破裂。新生儿结局包括预产期后6周内的新生儿死亡、脑室内出血、坏死性小肠结肠炎和支气管肺发育不良。 我们将检查埃索美拉唑是否可以降低血清sFlt-1和可溶性内皮素水平，我们将记录埃索美拉唑在这些妊娠中的安全性。本研究已获得伦理批准（方案V.2.4，M14/09/038，联邦广泛保证编号00001372，IRB 0005239），并在NHREC（ID 3649）和泛非临床试验注册中心（PACTR 201504000771349）注册。数据将在国际会议上提出，并发表在同行评审的期刊上。
Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals.