The Canadian STRIDER Randomised Controlled Trial of Sildenafil for Severe, Early-onset Fetal Growth Restriction

Abstract ObjectivesTo 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 <700g, and ≥1 of (i) abdominal circumference <10 th 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 <5 th percentile for GA. 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 the Dutch STRIDER trial signalled potential harm. NCT02442492 [registered 13/05/2015].ResultsBetween 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: 30 +1 weeks (sildenafil) vs 28 +6 weeks (placebo); p=0.555. Early trial termination precluded statistical power; however, there were signals of neither benefit nor harm. Data will contribute to an individual participant data meta-analysis.