The iSEARCH randomised controlled trial protocol: a pragmatic Australian phase III clinical trial of intrapartum sildenafil citrate to improve outcomes potentially related to intrapartum hypoxia

Abstract

Introduction We showed in a phase II randomised controlled trial (RCT) that oral sildenafil citrate in term labour halved operative birth for fetal distress. We outline the protocol for a phase III RCT (can intrapartum SildEnafil safely Avert the Risks of Contraction-induced Hypoxia? (iSEARCH)) of 3200 women in Australia to assess if sildenafil citrate reduces adverse perinatal outcomes related to intrapartum hypoxia.Methods and analysis iSEARCH will enrol 3200 Australian women in term labour to determine whether up to three 50 mg oral doses of sildenafil citrate versus placebo reduce the relative risk of a primary composite end point of 10 perinatal outcomes potentially related to intrapartum hypoxia by 35% (from 7% to 4.55%). Secondary aims are to evaluate reductions in the relative risk of emergency caesarean section or instrumental vaginal birth for fetal distress by 25% (from 20% to 15%) and in healthcare costs. To detect a 35% reduction in the primary outcome for an alpha of 0.05 and power of 80% with 10% dropout in each arm requires 3200 women (1600 in each arm). This sample size will also yield >90% power to detect a 25% reduction for the secondary outcome of any operative birth (caesarean section or instrumental vaginal birth) for fetal distress.Ethics and dissemination Ethical approval for the iSEARCH RCT was granted by the Hunter New England Human Research Ethics Committee (ref no: 2020/ETH02791). Results will be disseminated through websites, peer-reviewed publications, scientific meetings and social media, news outlets, television and radio.Trial registration number ACTRN12621000231842.