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

TY - JOUR

T1 - Halting the Canadian STRIDER randomised controlled trial of sildenafil for severe, early-onset fetal growth restriction

T2 - ethical, methodological, and pragmatic considerations

AU - von Dadelszen, Peter

AU - Audibert, François

AU - Bujold, Emmanuel

AU - Bone, Jeffrey N.

AU - Sandhu, Ash

AU - Li, Jing

AU - Kariya, Chirag

AU - Chung, Youkee

AU - Lee, Tang

AU - Au, Kelvin

AU - Skoll, M. Amanda

AU - Vidler, Marianne

AU - Magee, Laura A.

AU - Piedboeuf, Bruno

AU - Baker, Philip N.

AU - Lalji, Sayrin

AU - Lim, Kenneth I.

N1 - Funding Information: We acknowledge the funding support of the Canadian Institutes of Health Research (Grant Number: MOP-137077). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Early trial halting

KW - Fetal growth restriction

KW - Randomised controlled trial

KW - Sildenafil

UR - http://www.scopus.com/inward/record.url?scp=85133599742&partnerID=8YFLogxK

U2 - 10.1186/s13104-022-06107-y

DO - 10.1186/s13104-022-06107-y

M3 - Article

C2 - 35799272

AN - SCOPUS:85133599742

SN - 1756-0500

VL - 15

JO - BMC Research Notes

JF - BMC Research Notes

IS - 1

M1 - 244

ER -