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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 3,200 participants or records.
Read the paper
Related studies
- Drug repositioning: a brief overview
- Cyclic nucleotide phosphodiesterases in Drosophila melanogaster
- Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
- Current View on Green Tea Catechins Formulations, Their Interactions with Selected Drugs, and Prospective Applications for Various Health Conditions
- In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer’s Disease
- Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.