Can intrapartum SildEnafil safely Avert the Risks of Contraction-induced Hypoxia in labour? iSEARCH – a pragmatic Phase 3 Randomised Controlled Trial

Background
In Australia, almost 1 in 4 caesarean sections are performed for suspected fetal distress. A fetus can become distressed when the placenta is unable to adequately provide it with sufficient oxygen and nutrients during labour. The only therapeutic options when fetal distress develops are emergency operative birth by caesarean section (CS) or instrumental vaginal birth (IVB) – both of which can have serious consequences. Sildenafil Citrate (SC) preferentially dilates pelvic blood vessels and increases utero-placental blood flow. We propose that oral SC improves uterine perfusion in labour thus reducing adverse perinatal outcomes due to fetal distress.

Aim
The iSEARCH Trial will determine if, in women in labour at term receiving oral 50 mg SC vs placebo given in ≤3 doses, reduces a primary composite endpoint, determined up to 28 days after birth, of ten perinatal outcomes related to intrapartum hypoxia.

Progress
This Australia wide randomised controlled trial (RCT) rapidly completed recruitment of more than 3200 women. Data analysis continues, as does the follow up of biomarker results and neurodevelopmental outcomes.

Recruitment is complete and postnatal follow up continues.

Publications
Kumar S, Tarnow-Mordi W, Mol BW, Flenady V, Liley H, Badawi N, et al. 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. BMJ Open. 2024;14(9):e082943.

Kumar S, Tarnow-Mordi W, Mol B, Flenady V, Liley H, Badawi N, et al. The iSEARCH Trials of oral Sildenafil in labour: Protocol for a randomised trial in 3,200 Australian women and Rationale for an Individual Participant Data Prospective Meta-Analysis of trials in 14,000 women in high-income countries and a mega-trial of 50,000 women in low or middle-income countries. Research Square. 2022.

Dunn L, Greer R, Flenady V, Kumar S. Sildenafil in Pregnancy: A Systematic Review of Maternal Tolerance and Obstetric and Perinatal Outcomes. Fetal Diagn Ther. 2017;41(2):81-8.