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.

Kumar, S; Tarnow-Mordi, W; Mol, BW; Flenady, V; Liley, H; Badawi, N; Walker, SP; Hyett, J; Seidler, L; Callander, E; O'Connell, R

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.

Kumar, S Tarnow-Mordi, W Mol, BW Flenady, V Liley, H Badawi, N Walker, SP Hyett, J Seidler, L Callander, E

O'Connell, R

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Publisher:: BMJ
Publication Type:: Journal Article
Citation:: BMJ Open, 2024, 14, (9), pp. e082943
Issue Date:: 2024-09-28

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Field	Value	Language
dc.contributor.author	Kumar, S
dc.contributor.author	Tarnow-Mordi, W
dc.contributor.author	Mol, BW
dc.contributor.author	Flenady, V
dc.contributor.author	Liley, H
dc.contributor.author	Badawi, N
dc.contributor.author	Walker, SP
dc.contributor.author	Hyett, J
dc.contributor.author	Seidler, L
dc.contributor.author	Callander, E https://orcid.org/0000-0001-7233-6804
dc.contributor.author	O'Connell, R
dc.date.accessioned	2024-10-24T01:52:28Z
dc.date.available	2024-05-15
dc.date.available	2024-10-24T01:52:28Z
dc.date.issued	2024-09-28
dc.identifier.citation	BMJ Open, 2024, 14, (9), pp. e082943
dc.identifier.issn	2044-6055
dc.identifier.issn	2044-6055
dc.identifier.uri	http://hdl.handle.net/10453/181563
dc.description.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 publications, scientific meetings and social media, news outlets, television and radio. TRIAL REGISTRATION NUMBER: ACTRN12621000231842.
dc.format	Electronic
dc.language	eng
dc.publisher	BMJ
dc.relation.ispartof	BMJ Open
dc.relation.isbasedon	10.1136/bmjopen-2023-082943
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1117 Public Health and Health Services, 1199 Other Medical and Health Sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.classification	42 Health sciences
dc.subject.classification	52 Psychology
dc.subject.mesh	Humans
dc.subject.mesh	Sildenafil Citrate
dc.subject.mesh	Female
dc.subject.mesh	Pregnancy
dc.subject.mesh	Australia
dc.subject.mesh	Cesarean Section
dc.subject.mesh	Pragmatic Clinical Trials as Topic
dc.subject.mesh	Hypoxia
dc.subject.mesh	Fetal Distress
dc.subject.mesh	Humans
dc.subject.mesh	Fetal Distress
dc.subject.mesh	Cesarean Section
dc.subject.mesh	Pregnancy
dc.subject.mesh	Australia
dc.subject.mesh	Female
dc.subject.mesh	Pragmatic Clinical Trials as Topic
dc.subject.mesh	Sildenafil Citrate
dc.subject.mesh	Hypoxia
dc.subject.mesh	Humans
dc.subject.mesh	Sildenafil Citrate
dc.subject.mesh	Female
dc.subject.mesh	Pregnancy
dc.subject.mesh	Australia
dc.subject.mesh	Cesarean Section
dc.subject.mesh	Pragmatic Clinical Trials as Topic
dc.subject.mesh	Hypoxia
dc.subject.mesh	Fetal Distress
dc.title	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.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
utslib.for	1117 Public Health and Health Services
utslib.for	1199 Other Medical and Health Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated	2024-10-24T01:52:26Z
pubs.issue	9
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	9

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 publications, scientific meetings and social media, news outlets, television and radio. TRIAL REGISTRATION NUMBER: ACTRN12621000231842.

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http://hdl.handle.net/10453/181563