Pentaerithrityl tetranitrate (PETN) for secondary prevention of intrauterine growth restriction (PETN Trial)

四硝酸季戊四醇酯 (PETN) 用于宫内生长受限二级预防（PETN 试验）

• 批准号: 286545667
• 负责人: Professorin Dr. Tanja Groten
• 金额: --
• 依托单位: Klinik für Geburtsmedizin
• 依托单位国家: 德国
• 项目类别: Clinical Trials
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/286545667?language=en
• 关键词: Pentaerithrityl; tetranitrate; PETN; secondary; prevention

Affecting 10% of pregnancies, intrauterine growth restriction (IUGR) is the most important cause of perinatal mortality and morbidity. IUGR is defined as the pathologic restriction of intrauterine supply and the failure of the fetus to achieve its growth potential. Furthermore intrauterine malnutrition causes lifelong consequences as developmental origin of adult diseases. In the mother, IUGR is associated with vascular pathology, impaired placentation and the failure of decidual spiral artery remodelling, leading to impaired placental perfusion. Consequently, abnormal uterine flow, identified by duplex sonography at mid gestation, as well as maternal conditions associated with impaired vascular health, including previous IUGR, signifies the risk of developing IUGR during pregnancy. NO-donors as pentaerithrityl tetranitrate (PETN) reduce the impedance in the uteroplacental vessels and have been demonstrated to possess protecting effects on the endothelium. A randomized mono-center pilot study revealed a 38% relative risk reduction for IUGR or perinatal death (CI 95%: -1% to 63%) and a 70% reduction of preterm birth before 32 weeks of gestation (CI 95%: 9% to 92%) in the PETN intervention group. These data strongly suggest that PETN is a feasible drug to significantly improve the outcome in pregnancies compromised by placental insufficiency. To confirm the effects of PETN on pregnancy outcome 325 pregnant women at risk to develop IUGR will be enrolled into a prospective, multicenter, randomized, double-blind, placebo controlled, parallel group, interventional trial.

影响10%的妊娠，宫内生长受限（IUGR）是围产期死亡和发病的最重要原因。IUGR被定义为宫内供应的病理性限制和胎儿未能实现其生长潜能。此外，宫内营养不良作为成人疾病的发育根源，造成终生后果。在母亲中，IUGR与血管病理、胎盘受损和蜕膜螺旋动脉重构失败相关，导致胎盘灌注受损。因此，在妊娠中期通过双工超声检查发现的异常子宫流量，以及与血管健康受损相关的母体状况，包括以前的IUGR，都表明妊娠期间发生IUGR的风险。一氧化氮供体，如四硝酸季戊四酯（PETN），可降低子宫胎盘血管的阻抗，并已被证明对内皮具有保护作用。一项随机单中心试点研究显示，在PETN干预组中，IUGR或围产期死亡的相对风险降低了38% (CI 95%: -1%至63%)，妊娠32周前早产的相对风险降低了70% （CI 95%: 9%至92%）。这些数据强烈表明，PETN是一种可行的药物，可显著改善胎盘功能不全妊娠的结局。为了确认PETN对妊娠结局的影响，325名有IUGR风险的孕妇将被纳入一项前瞻性、多中心、随机、双盲、安慰剂对照、平行组、介入性试验。