The STRIDER Trial: A randomised controlled trial of sildenafil therapy In dismal prognosis early-onset intrauterine growth restriction

Severe early-onset in utero growth restriction (IUGR) affects babies in womb and is caused by reduced blood flow through the placenta. There is no treatment or cure for IUGR and the current clinical management involves intensive fetal surveillance with elective delivery performed when there is evidence of fetal distress and before the baby dies in the womb. At gestational ages remote from term premature delivery is associated with significant perinatal morbidity and mortality. Intact survival is less than 25% for an infant weighing 600g born at 25 completed gestation, and is still only approximately 50% up to 28 weeks gestation. The key determinants of death and morbidity in severe early-onset IUGR are gestational age at birth and birth weight. Importantly, an increase in neonatal survival of 2% is reported for each additional day in utero. Clearly, any intervention that prolongs gestational age could have significant beneficial effects on both survival and health. Sildenafil is a drug that acts to increase concentrations of nitric oxide (NO) and consequently increases vasodilatation of NO-responsive vessels. On the basis of previous work in animal models and evidence from previous studies of sildenafil in pregnant women, we believe that sildenafil may be a novel and innovative therapy for IUGR. We hypothesise that sildenafil causes vasodilatation of blood vessels in the womb, leading to increased blood and oxygen supply to the placenta and fetus. Sildenafil has a known safety profile and some data for safety in pregnancy. The STRIDER trial will determine whether sildenafil can improve fetal growth and prolong the gestation to delivery for severe-early onset IUGR. We believe that improved fetal growth is likely to delay the need for delivery and reduce the risk of prematurity-related death and disability. This landmark trial is the first of any treatment for this devastating condition.

Award Date: 19 June 2014
Award Value: €791,777
Principal Investigator: Professor Louise Kenny
Host Institution: University College Cork
Scheme: Health Research Awards - Definitive Intervention