Maternal sildenafil for severe early-onset fetal growth restriction: the Dutch multicentre placebo-controlled double-blind STRIDER-trial

OBJECTIVE: To study if the phosphodiesterase 5-inhibitor sildenafil
reduces the chance of perinatal mortality and morbidity in pregnancies complicated by severe early-onset fetal growth restriction.
STUDY DESIGN: Pregnant women between 20 and 30 weeks of
gestation with a singleton pregnancy were randomized to sildenafil
25 mg or placebo three times a day, up to delivery or 32 weeks of
gestation. The primary outcome was a composite of fetal and
neonatal mortality or major neonatal morbidity at hospital
discharge.
RESULTS: Between January 2015 and July 2018 216 (out of 360
planned) patients were randomized. In July 2018 recruitment was
discontinued at interim-analysis based on advice of the Data Safety
Monitoring Board due to serious concern that sildenafil may cause
harm to the neonates, whereas benefit on the primary outcome was
extremely unlikely. 108 Patients were allocated sildenafil, 108 to placebo. The primary outcome occurred in 59 patients (57%) allocated to
sildenafil and in 55 patients (52%) allocated to placebo (p¼0.53).
There was a non-significant trend towards more neonatal deaths in the
sildenafil group (21 (26%) versus 11 (15%); p¼0.07) that was associated with a higher number of cases with pulmonary hypertension
(mostly persistent pulmonary hypertension of the neonate (PPHN)):
15 (18%) versus four neonates (5.3%); p¼0.01). Retinopathy of
prematurity requiring laser or surgical treatment was also more
frequent (eight (13%) versus two (3%); p¼0.03). Other maternal and
secondary neonatal outcomes did not differ between groups.
CONCLUSION: Antenatal sildenafil administration, compared to placebo, did not reduce the chance of neonatal mortality and morbidity.
There was potential harm, although conclusions about a causal
relationship between sildenafil and adverse outcomes cannot be
inferred.