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

BMC Res Notes. 2022 Jul 7;15(1):244. doi: 10.1186/s13104-022-06107-y.

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: Early trial halting; Fetal growth restriction; Randomised controlled trial; Sildenafil.

Publication types

  • Meta-Analysis

MeSH terms

  • Canada
  • Female
  • Fetal Growth Retardation* / chemically induced
  • Fetal Growth Retardation* / drug therapy
  • Gestational Age
  • Humans
  • Placenta Growth Factor / therapeutic use
  • Pregnancy
  • Randomized Controlled Trials as Topic
  • Sildenafil Citrate / therapeutic use
  • Ultrasonography, Prenatal / adverse effects
  • Umbilical Arteries* / diagnostic imaging

Substances

  • Placenta Growth Factor
  • Sildenafil Citrate

Associated data

  • ClinicalTrials.gov/NCT02442492

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