STRIDER Canada: A Randomized Controlled Trial of Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction

Early-onset placental intrauterine growth restriction (EO IUGR) is associated with a high risk of perinatal morbidity and mortality. In association with reduced circulating placental growth factor (PLGF) EO IUGR results from abnormal placentation with inadequate remodelling of the maternal uteroplacental arteries. There is no known treatment for placental IUGR. Management involves intensive fetal surveillance with delivery with evidence of serious fetal compromise. However, remote from term, delivery is associated with significant perinatal mortality and morbidity. Sildenafil vasodilates the uteroplacental vessels of IUGR-affected pregnancies and may represent a novel therapy. Sildenafil has been used in pregnant women with pulmonary artery hypertension without adverse events, and has a good fetal safety profile from animal studies and a randomised controlled trial (RCT) of 17 women who received sildenafil (18 placebo-treated; non-significant increase in median birth weight of 367g after median 4.5d). We used sildenafil in a cohort of 12 women with severe EO IUGR as compassionate therapy. Compared with 17 sildenafil-naïve EO IUGR pregnancies, sildenafil appeared to improve daily fetal growth velocity (92% vs 41%, Fisher’s p=0.008; OR 16 [95% CI 2, 151]) and were more frequently live born (75% vs 35%, p=0.042, OR 6 [1.1, 28])). Therefore, there are sufficient data to support an RCT. We will target the fetus as patient.

STRIDER Canada is one of a consortium of STRIDER randomised controlled trials (RCTs) each of which is designed to determine whether or not maternal treatment with sildenafil citrate improves markers of perinatal wellbeing.

The overarching aim of the STRIDER Canada trial is to determine whether maternal treatment with oral sildenafil citrate improves perinatal outcomes in pregnancies complicated by early-onset IUGR without increasing risks to the mother.