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.

introductionWe 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 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.