Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Maternal sildenafil for severe early-onset fetal growth restriction: the dutch multicentre placebo-controlled double-blind strider-trial (#4)

Anouk pels 1 , Jan Derks 2 , Ayten Elvan 3 , Marjon De Boer 1 , Joris Van Drongelen 4 , Hans Duvekot 5 , Judith Van Laar 6 , Jimmy Van Eyck 7 , Salman Alnasiry 8 , Marieke Sueters 9 , Leonard Morssink 10 , Wes Onland 1 , Aleid Leemhuis 1 , Christa Naaktgeboren 1 , Wessel Ganzevoort 1
  1. Amsterdam University Medical Center, Amsterdam, The Netherlands
  2. Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  3. University Medical Center Groningen , Groningen, The netherlands
  4. Radbout University Medical Center, Nijmegen, The Netherlands
  5. Erasmus Medical Center , Rotterdam, The Netherlands
  6. Maxima Medisch Centrum, Veldhoven, The Netherlands
  7. Isala Klinieken , Zwolle, The Netherlands
  8. Maastricht University Medical Center, Maastricht, The Netherlands
  9. Leiden University medical Center , Leiden, The Netherlands
  10. Medisch Centrum Leeuwarden, leeuwarden, The Netherlands

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 66 patients (61%) allocated to sildenafil and in 58 patients (54%) allocated to placebo (p=0.31). There was a non-significant trend towards more neonatal deaths in the sildenafil group (21 (19%) versus 11 (10%); p=0.07) that was associated with a higher number of cases with pulmonary hypertension (mostly persistent pulmonary hypertension of the neonate (PPHN)): 16 (19%) versus four neonates (5%); p=0.01). Other maternal and secondary neonatal outcomes did not differ between groups.

Conclusions: 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.