TY - JOUR
T1 - Maternal sildenafil for severe fetal growth restriction (STRIDER)
T2 - a multicentre, randomised, placebo-controlled, double-blind trial
AU - Sharp, Andrew
AU - Cornforth, Christine
AU - Jackson, Richard
AU - Harrold, Jane
AU - Turner, Mark A
AU - Kenny, Louise C
AU - Baker, Philip N
AU - Johnstone, Edward D
AU - Khalil, Asma
AU - Von Dadelszon, Peter
AU - Papageorghiou, Aris T
AU - Alfirevic, Zarko
AU - Agarwal, Umber
AU - Willis, Elaine
AU - Mammarella, Silvia
AU - Masson, Geraldine
AU - Aquilina, Joe
AU - Greco, Elena
AU - Higgins, Sally
AU - Vinayagam, Dimuthu
AU - Shaw, Louise
AU - Stephens, Louise
AU - Howe, David
AU - Rand, Abby
AU - Patni, Shalini
AU - Mousa, Tommy
AU - Rabab, Asma
AU - Russell, Helen
AU - Hannon, Therese
AU - Fenn, Andrea
AU - Kilby, Mark
AU - Selman, Tara
AU - David, Anna
AU - Spencer, Rebecca
AU - Cohen, Kelly
AU - Breeze, Andrew
AU - McKelvey, Alastair
AU - Impey, Lawrence
AU - Loannou, Christos
AU - Stock, Sarah
AU - Poon, Liona
AU - Pasupathy, Dharmintra
AU - Webster, Louise
AU - Bugg, George
AU - STRIDER group
PY - 2018/2
Y1 - 2018/2
N2 - Background Severe early-onset fetal growth restriction can lead to a range of adverse outcomes including fetal or neonatal death, neurodisability, and lifelong risks to the health of the affected child. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates the actions of nitric oxide, which leads to vasodilatation of the uterine vessels and might improve fetal growth in utero. Methods We did this superiority, placebo-controlled randomised trial in 19 fetal medicine units in the UK. We used random computer allocation (1:1) to assign women with singleton pregnancies between 22 weeks and 0 days' gestation and 29 weeks and 6 days' gestation and severe early-onset fetal growth restriction to receive either sildenafil 25 mg three times daily or placebo until 32 weeks and 0 days' gestation or delivery. We stratified women by site and by their gestational age at randomisation (before week 26 and 0 days or at week 26 and 0 days or later). We defined fetal growth restriction as a combination of estimated fetal weight or abdominal circumference below tenth percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days. This study is registered with BioMed Central, number ISRCTN 39133303. Findings Between Nov 21, 2014, and July 6, 2016, we recruited 135 women and randomly assigned 70 women to sildenafil and 65 women to placebo. We found no difference in the median randomisation to delivery interval between women assigned to sildenafil (17 days [IQR 7–24]) and women assigned to placebo (18 days [8–28]; p=0·23). Livebirths (relative risk [RR] 1·06, 95% CI 0·84 to 1·33; p=0·62), fetal deaths (0·89, 0·54 to 1·45; p=0·64), neonatal deaths (1·33, 0·54 to 3·28; p=0·53), and birthweight (−14 g,–100 to 126; p=0·81) did not differ between groups. No differences were found for any other secondary outcomes. Eight serious adverse events were reported during the course of the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil. Interpretation Sildenafil did not prolong pregnancy or improve pregnancy outcomes in severe early-onset fetal growth restriction and therefore it should not be prescribed for this indication outside of research studies with explicit participants' consent. Funding National Institute for Health Research and Medical Research Council.
AB - Background Severe early-onset fetal growth restriction can lead to a range of adverse outcomes including fetal or neonatal death, neurodisability, and lifelong risks to the health of the affected child. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates the actions of nitric oxide, which leads to vasodilatation of the uterine vessels and might improve fetal growth in utero. Methods We did this superiority, placebo-controlled randomised trial in 19 fetal medicine units in the UK. We used random computer allocation (1:1) to assign women with singleton pregnancies between 22 weeks and 0 days' gestation and 29 weeks and 6 days' gestation and severe early-onset fetal growth restriction to receive either sildenafil 25 mg three times daily or placebo until 32 weeks and 0 days' gestation or delivery. We stratified women by site and by their gestational age at randomisation (before week 26 and 0 days or at week 26 and 0 days or later). We defined fetal growth restriction as a combination of estimated fetal weight or abdominal circumference below tenth percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days. This study is registered with BioMed Central, number ISRCTN 39133303. Findings Between Nov 21, 2014, and July 6, 2016, we recruited 135 women and randomly assigned 70 women to sildenafil and 65 women to placebo. We found no difference in the median randomisation to delivery interval between women assigned to sildenafil (17 days [IQR 7–24]) and women assigned to placebo (18 days [8–28]; p=0·23). Livebirths (relative risk [RR] 1·06, 95% CI 0·84 to 1·33; p=0·62), fetal deaths (0·89, 0·54 to 1·45; p=0·64), neonatal deaths (1·33, 0·54 to 3·28; p=0·53), and birthweight (−14 g,–100 to 126; p=0·81) did not differ between groups. No differences were found for any other secondary outcomes. Eight serious adverse events were reported during the course of the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil. Interpretation Sildenafil did not prolong pregnancy or improve pregnancy outcomes in severe early-onset fetal growth restriction and therefore it should not be prescribed for this indication outside of research studies with explicit participants' consent. Funding National Institute for Health Research and Medical Research Council.
U2 - 10.1016/S2352-4642(17)30173-6
DO - 10.1016/S2352-4642(17)30173-6
M3 - Article
SN - 2352-4642
SP - 93
EP - 102
JO - The Lancet Child & Adolescent Health
JF - The Lancet Child & Adolescent Health
ER -