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Halting the Canadian STRIDER randomised controlled trial of sildenafil for severe, early-onset fetal growth restriction: ethical, methodological, and pragmatic considerations

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journal contribution
posted on 05.08.2022, 08:39 authored by Peter von Dadelszen, Francois Audibert, Emmanuel Bujold, Jeffrey N Bone, Ash Sandhu, Jing Li, Chirag Kariya, Youkee Chung, Tang Lee, Kelvin Au, M Amanda Skoll, Marianne Vidler, Laura A Magee, Bruno Piedboeuf, Philip N Baker, Sayrin Lalji, Kenneth Lim

Objectives

To determine the efficacy and safety of sildenafil citrate to improve outcomes in pregnancies complicated by early-onset, dismal prognosis, fetal growth restriction (FGR). Eligibility: women ≥ 18 years, singleton, 18 + 0–27 + 6 weeks’ gestation, estimated fetal weight < 700 g, low PLFG, and ≥ 1 of (i) abdominal circumference < 10th percentile for gestational age (GA); or (ii) reduced growth velocity and either abnormal uterine artery Doppler or prior early-onset FGR with adverse outcome. Ineligibility criteria included: planned termination or reversed umbilical artery end-diastolic flow. Eligibility confirmed by placental growth factor (PLGF) < 5 th percentile for GA measured post randomization. Women randomly received (1:1) either sildenafil 25 mg three times daily or matched placebo until either delivery or 31 + 6 weeks. Primary outcome: delivery GA. The trial stopped early when Dutch STRIDER signalled potential harm; despite distinct eligibility criteria and IRB and DSMB support to continue, because of futility. NCT02442492 [registered 13/05/2015].


Results

Between May 2017 and June 2018, 21 (90 planned) women were randomised [10 sildenafil; 11 placebo (1 withdrawal)]. Baseline characteristics, PLGF levels, maternal and perinatal outcomes, and adverse events did not differ. Delivery GA: 26 + 6 weeks (sildenafil) vs 29 + 2 weeks (placebo); p = 0.200. Data will contribute to an individual participant data meta-analysis.

Funding

Canadian Institutes of Health Research (Grant Number: MOP-137077)

History

Author affiliation

College of Life Sciences, University of Leicester

Version

VoR (Version of Record)

Published in

BMC RESEARCH NOTES

Volume

15

Issue

1

Publisher

SPRINGERNATURE

issn

1756-0500

eissn

1756-0500

Acceptance date

13/06/2022

Copyright date

2022

Available date

05/08/2022

Spatial coverage

England

Language

English