IA 6 Pentaerithrityl tetranitrate (PETN) for secondary prevention of intrauterine growth restriction (PETN-Trial)

Abstract

Aim Affecting approximately 10% of pregnancies, intrauterine growth restriction (IUGR), is the most important cause of perinatal mortality and morbidity, affecting short term and long term outcome of the newborns with lifelong consequences as developmental origin of adult diseases Impaired placental function determined by insufficient transformation of the uterine arteries and mal-perfusion of the placenta is the leading cause of IUGR. Although, consequently, screening for placental insufficiency based on uterine artery Doppler measurement is well established, so far there is no treatment option for pregnancies threatened by IUGR. The organic nitrate pentaerithrityl tetranitrate (PETN) is widely used for the treatment of cardiovascular disease and has been shown to possess potent protecting effects at the endothelium by enhancing the expression of the antioxidant genes, like heme oxygenase-1 (HO-1) in human endothelial cells. In a randomized placebo controlled pilot study our group could demonstrate a risk reduction of 39% (relative risk RR = 0.609, 95% CI 0.367 to 1.011) for the development of IUGR and IUGR or death (RR = 0.615, 95% CI 0.378 to 1.000) by delivering PETN to patients with impaired uterine artery Doppler at mid gestation. (Schleussner, 2014) To confirm these results a prospective randomized placebo controlled double-blinded multicentre trial was now initiated. Approach Inclusion criteria are abnormal uterine artery Doppler ultrasound, defined by a mean PI > 1.6, at 190 to 226 weeks of gestation in singleton pregnancies. Included patients will be monitored at a 4;weeks schedule. Dopplerparameters, manternal und fetal clinical outcome will be assessed. Outcome measures Development of IUGR (defined by birth weight 10 th percentile and impaired uterine perfusion identified by a mean PI of >1.6). Severe IUGR ( 3 rd centile), placental abruption, birth weight below the 3 rd , 5 th and 10 th centile, development of IUGR requiring delivery before 34 weeks‘ gestation, the rate of neonatal intensive care unit admission, and spontaneous preterm delivery Results Patient enrollment will be started in July 2017. The proposed recruitment period is 18 month. Results are expected in 2020. DFG GR 1955 4–1