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Trial question
What is the effect of intrapartum maternal sildenafil citrate in women with term pregnancies planning vaginal birth?
Study design
Multi-center
Double blinded
RCT
Population
3250 female patients.
Inclusion criteria: adult women with term pregnancies planning vaginal birth.
Key exclusion criteria: women with triplet or higher-order multifetal gestation; monochorionic twins; receipt of any type of nitrate-containing medications or other phosphodiesterase inhibitors; severe renal or hepatic impairment.
Interventions
N=1625 sildenafil (50 mg sildenafil citrate PO every 8 hours).
N=1625 placebo (matching placebo PO every 8 hours).
Primary outcome
Composite outcome of adverse perinatal events, icluding intrapartum stillbirth, neonatal death, Apgar score < 4 at 5 minutes, acidosis at birth, hypoxic-ischemic encephalopathy, neonatal seizures, neonatal respiratory support > 4 hours, neonatal unit admission > 48 hours, persistent pulmonary hypertension of newborn, or meconium aspiration syndrome
5.1%
5.2%
5.2 %
3.9 %
2.6 %
1.3 %
0.0 %
Sildenafil
Placebo
No significant
difference ↔
No significant difference in composite outcome of adverse perinatal events, icluding intrapartum stillbirth, neonatal death, Apgar score < 4 at 5 minutes, acidosis at birth, hypoxic-ischemic encephalopathy, neonatal seizures, neonatal respiratory support > 4 hours, neonatal unit admission > 48 hours, persistent pulmonary hypertension of the newborn, or meconium aspiration syndrome (5.1% vs. 5.2%; RR 1.02, 95% CI 0.75 to 1.37).
Secondary outcomes
No significant difference in umbilical cord artery pH < 7.0 (0.7% vs. 0.3%; RR 2.28, 95% CI 0.81 to 6.47).
No significant difference in neonatal respiratory support > 4 hours (2.3% vs. 2.9%; RR 0.81, 95% CI 0.53 to 1.25).
No significant difference in emergency Cesarean delivery or instrumental vaginal birth for fetal distress (21.1% vs. 18.8%; RR 1.12, 95% CI 0.98 to 1.29).
Safety outcomes
No significant differences in adverse events, any other serious maternal or neonatal outcomes.
Conclusion
In adult women with term pregnancies planning vaginal birth, sildenafil was not superior to placebo with respect to the composite outcome of adverse perinatal events, icluding intrapartum stillbirth, neonatal death, Apgar score < 4 at 5 minutes, acidosis at birth, hypoxic-ischemic encephalopathy, neonatal seizures, neonatal respiratory support > 4 hours, neonatal unit admission > 48 hours, persistent pulmonary hypertension of the newborn, or meconium aspiration syndrome.
Reference
Sailesh Kumar, William Tarnow-Mordi, Ben W Mol et al. Intrapartum Sildenafil to Improve Perinatal Outcomes: A Randomized Clinical Trial. JAMA. 2025 Jun 9. Online ahead of print.
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