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



Liauw, Jessica, Groom, Katie, Ganzevoort, Wessel, Gluud, Christian, McKinlay, Christopher JD, Sharp, Andrew ORCID: 0000-0003-3396-7464, Mackay, Laura, Kariya, Chirag, Lim, Ken, von Dadelszen, Peter
et al (show 30 more authors) (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).

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Statistical Analysis Plan- STRIDER_R1_Oct 18 2021.docx - Accepted Version

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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
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: 08 Sep 2022 23:11
DOI: 10.1186/s13643-021-01849-5
URI: https://livrepository.liverpool.ac.uk/id/eprint/3144600