RELEVANCE: Severe, early-onset fetal growth restriction (FGR) due to placental insufficiency is associated with a high risk of perinatal morbidity with long-lasting sequelae and mortality. Placental insufficiency is the result of abnormal formation and function of the placenta (placentation) with inadequate remodelling of the maternal spiral (uteroplacental) arteries. There is currently no therapy available with demonstrated effectiveness. Evidence suggests Sildenafil citrate improves uteroplacental blood flow, growth, and meaningful outcomes.
OBJECTIVE: To evaluate the effectiveness of sildenafil (versus placebo) in achieving healthy perinatal survival.
DESIGN: Multicenter nationwide randomized clinical trial.
PATIENTS: Women with a singleton pregnancy between 20 and 30 weeks with severe fetal growth restriction of likely placental origin, and with estimated significant likelihood of perinatal death.
INTERVENTIONS: Sildenafil 25mg or placebo tablet orally three times daily.
PRIMARY STUDY OUTCOME: Perinatal healthy survival, i.e. survival without severe neonatal morbidity at term age.
ECONOMIC EVALUATION: we will calculate the cost per additional achieved case of intact perinatal survival to term age. Costs of medication will be part of this analysis.
POWER CALCULATION: To detect an increase in healthy survival from 29% to 44% with 80% power and alpha 0.05, 354 women (two groups of 177) have to be included.