Ursodeoxycholic acid versus placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP) to improve perinatal outcomes: protocol for a randomised controlled trial (PITCHES)

Trials. 2018 Nov 27;19(1):657. doi: 10.1186/s13063-018-3018-4.

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy and presents with maternal pruritus, raised concentrations of serum bile acids and abnormal liver function tests. ICP is associated with increased rates of spontaneous and iatrogenic preterm labour, fetal hypoxia, meconium-stained amniotic fluid and intrauterine death. Some clinicians treat ICP with ursodeoxycholic acid (UDCA) to improve maternal pruritus and biochemical abnormalities. However, there are currently no data to support the use of UDCA to improve pregnancy outcome as none of the trials performed to date have been powered to address this question.

Methods: The PITCHES trial is a triple-masked, placebo-controlled randomised trial, to evaluate UDCA versus placebo in women with ICP between 20 + 0 to 40 + 6 weeks' gestation. The primary objective of the trial is to determine if UDCA treatment of women with ICP between 20 + 0 and 40 + 6 weeks' gestation reduces the primary perinatal outcome: a composite of perinatal death (as defined by in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (less than 37 weeks' gestation) or neonatal unit admission for at least 4 h (from infant delivery until hospital discharge). The secondary objectives of the trial are (1) to investigate the effect of UDCA on other short-term outcomes for both mother and infant and (2) to assess the impact of UDCA on health care resource use, in terms of the total number of nights for mother and infant, together with level of care.

Discussion: Current practice in the UK at the time of trial commencement for the treatment of ICP is inconsistent, with some units routinely prescribing UDCA, others prescribing very little and the remainder offering it variably. Our previous pilot trial of UDCA in women with ICP demonstrated that the trial would be feasible, and the research question remains active and unanswered. Results are highly likely to influence clinical practice, through direct management and impact on national and international guidelines.

Trial registration: ISRCTN registry, ID: ISRCTN91918806 . Prospectively registered on 27 August 2015.

Keywords: Cholestasis; Perinatal; Pregnancy; Stillbirth; Ursodeoxycholic acid.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Cholagogues and Choleretics / adverse effects
  • Cholagogues and Choleretics / therapeutic use*
  • Cholestasis, Intrahepatic / blood
  • Cholestasis, Intrahepatic / diagnosis
  • Cholestasis, Intrahepatic / drug therapy*
  • Cholestasis, Intrahepatic / mortality
  • England
  • Female
  • Fetal Death / prevention & control
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Multicenter Studies as Topic
  • Perinatal Death / prevention & control
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / mortality
  • Premature Birth / prevention & control
  • Randomized Controlled Trials as Topic
  • Stillbirth
  • Time Factors
  • Treatment Outcome
  • Ursodeoxycholic Acid / adverse effects
  • Ursodeoxycholic Acid / therapeutic use*
  • Wales

Substances

  • Cholagogues and Choleretics
  • Ursodeoxycholic Acid

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy