BACKGROUND AND PURPOSE:

• There are currently no interventions for nonreassuring fetal status aside from delivery if unresolved
• In this phase II clinical trial, Turner et al. (AJOG, 2020) examined whether sildenafil citrate could be used to reduce the number of emergency operative births for fetal compromise

METHODS:

• Phase II double-blind randomized controlled trial (RCT)
  • RIDSTRESS (“Reducing the Incidence of Fetal Distress with Sildenafil Citrate”) trial
• Participants
  • 18 to 50 years of age
  • Term pregnancy (≥37 weeks)
  • In early labor (cervical dilation <4cm) or undergoing scheduled induction of labor
• Exclusion criteria
  • Preeclampsia or on antihypertensive medication | >1 previous cesarean | SGA | Contraindication to sildenafil
• Interventions
  • Sildenafil citrate group
    • 50 mg of sildenafil citrate orally every 8 hours up to 150 mg
  • Control group
    • Placebo
• Study design
  • Intrapartum fetal monitoring (based on RANZCOG guidelines)
  • Analysis was by intention-to-treat
• Primary outcomes
  • Emergency operative birth for intrapartum fetal compromise
    • Either by cesarean or instrumental vaginal birth
  • Mean indices of fetal and uteroplacental perfusion using Doppler ultrasound
• Statistical analysis
  • 288 women per group (>90% power, alpha of 0.05) to demonstrate 50% change in primary outcome | 320 per group needed to account for 10% potential drop out rate

RESULTS:

• 300 women were randomized
  • Sildenafil citrate: 150 women
  • Control: 150 women
• Sildenafil citrate reduced the risk of emergency operative birth (p=0.0004)
  • Sildenafil citrate: 18%
  • Control: 36.7%
  • Relative risk (RR) 0.49 (95% CI, 0.33 to 0.73)
  • Number needed to treat: 5 (95% CI, 3 to 11)
• Sildenafil citrate reduced the risk of meconium-stained liquor or pathologic fetal heart rate patterns (p=0.0005)
  • Sildenafil citrate: 25.3%
  • Control: 44.7%
  • RR 0.57 (95% CI 0.41 to 0.79)
• Evidence for the following effects was found to be inconclusive
  • Fetal scalp sampling rates (p=0.06)
    • Sildenafil citrate: 2.0%
    • Control: 6.7%
    • RR 0.30 (95% CI, 0.08 to 1.07)
  • Adverse neonatal outcome (p=0.89)
    • Sildenafil citrate: 20.7%
    • Control: 21.3%
    • RR 0.97 (95% CI 0.62 to 1.50)
• Cord blood levels of sildenafil citrate (or metabolite): 3.6% of maternal level
• No significant differences detected for
  • Maternal adverse events
  • Indices of fetal and uteroplacental perfusion (only studied in 71 women)

CONCLUSION:

• In this phase II trial, sildenafil citrate
  • Reduced the risk of emergency operative birth by 51%
  • Reduced the risk of meconium-stained liquor or pathologic fetal heart rate patterns by 43%
• However, results were inconclusive for adverse and other outcomes, so while promising, authors acknowledge that larger phase III trials are necessary sildenafil citrate can be used clinically

Learn More – Primary Sources:

Safety and efficacy of sildenafil citrate to reduce operative birth for intrapartum fetal compromise at term: a phase 2 randomized controlled trial

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