1. 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.
- Author
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Kumar S, Tarnow-Mordi W, Mol BW, Flenady V, Liley H, Badawi N, Walker SP, Hyett J, Seidler L, Callander E, and O'Connell R
- Subjects
- Humans, Female, Pregnancy, Australia, Cesarean Section, Pragmatic Clinical Trials as Topic, Hypoxia prevention & control, Fetal Distress, Sildenafil Citrate therapeutic use, Sildenafil Citrate administration & dosage
- 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 i ntrapartum S ild E nafil safely A vert the R isks of C ontraction-induced H ypoxia? (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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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