Short-term outcomes of phosphodiesterase type 5 inhibitors for fetal growth restriction: a study protocol for a systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis

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Liauw, Jessica, Groom, Katie, Ganzevoort, Wessel, Gluud, Christian, McKinlay, Christopher JD, Sharp, Andrew, Mackay, Laura, Kariya, Chirag, Lim, Ken, von Dadelszen, Peter et al (show 30 more authors) , Limpens, Jacqueline, Jakobsen, Janus C, Audibert, Francois, Alfirevic, Zarko, Baker, Philip, Bujold, Emmanuel, Chung, Youkee, Cornforth, Christine, Ganzevoort, Wessel, Gordijn, Sanne J, Groom, Katie, Gluud, Christian, Jakobsen, Janus C, Johnstone, Edward D, Kariya, Chirag, Kenny, Louise ORCID: 0000-0002-9011-759X, Lee, Tang, Li, Larry, Liauw, Jessica, Lim, Ken, Magee, Laura, Mackay, Laura, McCowan, Lesley, McKinlay, Chris, Mol, Ben W, Onland, Wes, Papageorghiou, Aris, Pels, Anouk, Sharp, Andrew ORCID: 0000-0003-3396-7464 and von Dadelszen, Peter (2021) Short-term outcomes of phosphodiesterase type 5 inhibitors for fetal growth restriction: a study protocol for a systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis. Systematic Reviews, 10 (1). 305-.

Text Statistical Analysis Plan- STRIDER_R1_Oct 18 2021.docx - Author Accepted Manuscript Download (178kB)

Abstract

<jats:sec> <jats:title>Abstract</jats:title> </jats:sec><jats:sec> <jats:title>Background</jats:title> <jats:p>Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">Clinicaltrials.gov</jats:ext-link> and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight <jats:italic>z</jats:italic>-scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE.</jats:p> </jats:sec><jats:sec> <jats:title>Discussion</jats:title> <jats:p>This pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction.</jats:p> </jats:sec><jats:sec> <jats:title>Systematic review registration</jats:title> <jats:p>PROSPERO (CRD42017069688).</jats:p> </jats:sec>

Item Type:	Article
Uncontrolled Keywords:	Fetal growth restriction, Phosphodiesterase type 5 inhibitor, Randomised clinical trial, Trial sequential analysis, Aggregate meta-analysis, Individual patient data meta-analysis
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	06 Dec 2021 08:08
Last Modified:	18 Jan 2023 21:23
DOI:	10.1186/s13643-021-01849-5
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3144600