RidStress 2 randomised controlled trial protocol: an Australian phase III clinical trial of intrapartum sildenafil citrate or placebo to reduce emergency caesarean birth for fetal distress in women with small or suboptimally grown infants at term (≥37 weeks)

Abstract

Introduction Small for gestational age (SGA) infants are at increased risk of fetal distress in labour requiring emergency operative birth (by caesarean section (CS), vacuum or forceps). We have previously shown that maternal oral sildenafil citrate (SC) in labour halves the need for operative birth for suspected fetal distress in women with appropriately grown term infants.Methods and analysis RidStress 2 is a phase III randomised, double-blinded, placebo-controlled trial of 660 women with an SGA or suboptimally grown fetus (estimated fetal weight or abdominal circumference<10th centile for gestational age) planning a vaginal birth at term. The trial will determine whether oral intrapartum SC (50 mg eight hourly) reduces the relative risk of emergency CS for fetal distress compared with placebo. The primary outcome is CS for fetal distress, and the secondary outcomes are any operative birth for fetal distress, cost-effectiveness of SC treatment and 2-year childhood neurodevelopmental outcomes. To detect a 33% reduction in the primary outcome from 30% to 20% for an alpha of 0.05 and power of 80% with 10% dropout, requires approximately 660 women (330 in each arm). This sample size will also yield >90% power to detect a similar reduction for the secondary outcome of any operative birth (CS or instrumental vaginal birth) for fetal distress.Ethics and dissemination Ethics approval was granted by the Mater Misericordiae Limited Human Research Ethics Committee (EC00332) on 11 September 2020. We plan to disseminate the results of this randomised controlled trial through presentations at scientific meetings and peer-reviewed journals, adhering to all relevant reporting guidelines.Trial registration number RidStress 2 is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000354886, 29/03/2021) and the Therapeutic Goods Association of Australia (date registered: 16 March 2021).