BMC Research Notes (Jul 2022)

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

  • Peter von Dadelszen,
  • François 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 I. Lim

DOI
https://doi.org/10.1186/s13104-022-06107-y
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 6

Abstract

Read online

Abstract 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.

Keywords