Grand Rounds

RIDSTRESS RCT Results: Can Sildenafil Reduce Emergency Operative Births for Fetal Compromise?

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

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

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)

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

< Previous

Next >