PITCHES RCT: Ursodeoxycholic Acid and Intrahepatic Cholestasis of Pregnancy

BACKGROUND AND PURPOSE:

  • Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse perinatal outcomes
    • Stillbirth, preterm birth, and NICU admission
  • Ursodeoxycholic acid is a widely used treatment for ICP, although data in limited
  • Chappell et al. (The Lancet, 2019) investigated whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with ICP

METHODS:

  • Pragmatic double-blind, multicenter, randomized placebo-controlled trial (RCT)
  • Participants: Women with ICP (based on pruritis and bile acid above normal limit of local lab)
    • ≥18 years
    • GA between 20w0d and 40w6d
    • Singleton or twin pregnancy and no known lethal fetal anomalies
  • Interventions (from enrollment till birth)
    • Ursodeoxycholic acid group: 500 mg (1 tablet) twice a day with adjustment based on clinician’s discretion (maximum four tablets | minimum one tablet)
    • Control group: placebo
  • Primary outcome: Composite of
    • Perinatal death: IUFD or neonatal death up to 7 days after birth
    • Preterm delivery: <37 weeks
    • NICU admission for at least 4 hours

RESULTS:

  • Primary outcome analysis
    • Ursodeoxycholic acid group: included 304 women and 322 infants
    • Control group: 300 women and 318 infants
  • The primary outcome occurred in
    • Ursodeoxycholic acid group: 23%
    • Control group: 27%
    • Adjusted risk ratio (RR) 0.85 (95% CI, 0.62 to 1.15)
    • Serious events were recorded but none were attributable to the treatment
  • Maternal itch score was significantly reduced in the ursodeoxycholic acid group but “had no clinically meaningful effect” (itch score measured as the worst episode of itch over a day on a 100-mm visual analogue scale)
    • Mean difference −5.7 mm (95% CI, −9.7 to −1.7; p=0·0054)
  • Bile acid concentration reduction was less in the ursodeoxycholic acid group vs placebo (p=0.030)

CONCLUSION:

  • Compared to placebo, ursodeoxycholic acid did not impact risk for adverse events related to ICP
  • The authors of this study suggest that the use of ursodeoxycholic acid for ICP should be reconsidered because

Ursodeoxycholic acid does not seem to have any significant clinical benefit when used routinely for treatment of women with intrahepatic cholestasis of pregnancy

Learn More – Primary Sources:

Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial

Ursodeoxycholic acid for intrahepatic cholestasis in pregnancy