PITCHES

Phase III trial in IntrahepaTic CHolestasis of pregnancy (ICP) to Evaluate urSodeoxycholic acid (UDCA) in improving perinatal outcomes

Trial started: 2015  Trial ended: 2019 

Summary

Objectives

To evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

Methods

A multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial conducted in 33 UK maternity units. Women aged ?18 years with intrahepatic cholestasis of pregnancy, between 20+0 and 40+6 weeks' gestation, with a singleton or twin pregnancy and no known lethal fetal anomaly were randomised to receive ursodeoxycholic acid tablets or matched placebo tablets at an equivalent dose of 1000 mg daily, titrated as needed.

Outcome measures

Primary outcome: A composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days), preterm delivery (<37 weeks' gestation) or neonatal unit admission for at least 4 hours from birth until hospital discharge. Each infant was counted once within the composite.

Results

Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid group and 300 women to the placebo group. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 of 318 infants) in the placebo group (adjusted risk ratio 0.85, 95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group.

Conclusions

In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there was no evidence that it was effective in reducing the composite of adverse perinatal outcomes.

Adapted from: Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid to reduce adverse perinatal outcomes for intrahepatic cholestasis of pregnancy: the PITCHES RCT. Efficacy and Mechanism Evaluation. 2020;7(9). https://doi.org/10.3310/eme07090. © Queen's Printer and Controller of HMSO 2020. Adapted for presentation on this website