A randomised Trial of URsodeoxycholic acid versus RIFampicin in severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC study.

Ethics Committee Project Number
HREC/18/@CHN/36 – RES-20-0000742X
Approved by
Monash Health
Research area
Women's Health
Brief outline of the study
To determine the effectiveness of two treatments, Ursodeoxycholic Acid (UDCA) and Rifampicin, in the reduction of itch, the major symptom of the disorder, as well as on biochemical markers of ICP, and the maternal and neonatal microbiota and faecal metabolite profiles.
We will also use the opportunity of recruitment to examine the feasibility of recruitment to a later trial powered on neonatal outcomes as to whether planned early delivery or expectant management impacts on such outcomes.
We will also perform whole exome sequencing (WES) for mutations associated with the cholestatic phenotype in women consenting to the study, which will later inform targeted therapy. The exome analysis will allow study of all of the currently described candidate gene mutations / variants.

Keywords
pregnancy, intrahepatic cholestasis, Rifampicin, Ursodeoxycholic acid
Recruitment start date
Thursday, 8 December, 2022
Recruitment end date
Sunday, 31 December, 2023
Contact person title
Prof
Contact person full name
Ben W. Mol
Contact email
Ben.Mol@monash.edu
Contact phone number
03 9594 5383
Website link
https://www.monash.edu/medicine/scs/research/evidence-based-womens-health-care
Do you have advertising approval:
Yes
Current number of recruits:
45
Recruitment target:
108
Principal Investigator title:
Professor
Principal Investigator full name:
Ben W. Mol
Principal Investigator PURE profile link:
https://research.monash.edu/en/persons/ben-w-mol
Contact person role:
Principal Investigator
Local reference number:
RES-20-0000-742X
Type of study:
PI initiated
Number of study visits:
7 visits
Duration of study visits period:
28 weeks

Inclusion criteria:
Women will be eligible to participate in the Pre-TURRIFIC study if they are:
- pregnant, less than 20 weeks gestation
- at increased risk of ICP (defined as previous ICP in self, mother or sister)
- not yet developed ICP
- willing to provide written consent

Exclusion criteria:

  • non-viable pregnancy
  • greater than 20 weeks gestation
  • diagnosed with ICP in the current pregnancy
  • have an active Hepatitis A or Hepatitis B infection, or are a Hepatitis B or C carrier
  • are known to have α-1-antitrypsin deficiency, autoimmune hepatitis, or other known
    active liver disorder
  • are already taking medication that can cause changes in liver tests
  • are not willing to provide written consent

Phase:
Phase III
Objective:
This study will be comparing two medications to treat a rare liver condition in pregnancy “severe early onset Intrahepatic Cholestasis of Pregnancy (ICP)”.
Research question:
Will Rifampicin (RIF) compared with Ursodeoxycholic Acid (UDCA) reduce the degree of pruritus as measured by worst itch in the previous 24 hours assessed on a patient-recorded visual analogue scale? Will RIF compared with UDCA improve short-term outcomes for both mother an infant in severe early onset ICP, including the length of gestation and the incidence of caesarean section and preterm birth?
Study design:
Multicentre randomised open label controlled study
Study population:
Women with a singletono pregnancy and current severe early onset ICP diagnosed between 14+0 and 33+6 weeks of gestation.
Description of intervention:
Rifampicin 300 mg bd orally
Outcome measures:
Pruritus defined as worst itch in the previous 24 hours assessed on a patient-recorded visual analogue scale. Pruritus will be evaluated at one week after trial entry and then on a monthly basis to 28 weeks, and then weekly to delivery.
Sponsor:
The University of Adelaide, Adelaide SA 5005