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

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2018-004011-44-FI
• Date of registration: 26/09/2019
• Prospective Registration: Yes
• Primary sponsor: The University of Adelaide
• Public title: Trial of URsodeoxycholic acid versus RIFampicin in severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC study
• Scientific title: A randomised trial of URsodeoxycholic acid versus RIFampicin in severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC study, comparing their effectiveness in the reduction of pruritis. - TURRIFIC
• Date of first enrolment: 20/05/2020
• Target sample size: 108
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004011-44
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Finland, Netherlands, Sweden, United Kingdom

Contacts

• Name: Physician In Chief
• Affiliation: Helsinki University

• Name: Physician In Chief
• Affiliation: Helsinki University

Key inclusion & exclusion criteria

Inclusion criteria:
Women will be considered eligible for inclusion into the trial with the following criteria:
• Severe ICP (defined as pruritus with raised total serum BA =40 µmol/L) confirmed (see note below on standardisation of bile acid assays)
• Viable pregnancy between 14+0 and 33+6 weeks gestation inclusive (see note below on gestational age)
• No known lethal fetal anomaly
• Singleton pregnancy
• Obstetric care in a consultant-led unit
• Aged 18 years or over
• Written informed consent has been obtained

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
A potential participant who meets any of the following criteria will be excluded from participation in this study:
• A decision has already been made for delivery within the next 48 hours
• There is allergy to any component of the UDCA or RIF tablets
• The woman is taking other medication that has a significant interaction with rifampicin treatment
• There is a multi-fetal gestation
• There is laboratory-confirmed active hepatitis A or hepatitis B, or positive serology for hepatitis C
• There is current pre-eclampsia (ISSHP criteria)
• There is a known primary hepatic disorder, including a-1-antitrypsin deficiency and autoimmune hepatitis, including primary biliary cholangitis
• The woman is on current medication causing deranged liver enzymes
• The woman is unwilling for her baby to have standard Vitamin K administration at birth
• The woman has previously participated in TURRIFIC



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

Intrahepatic Cholestasis of Pregnancy (ICP) is an serious liver condition in pregnancy. The main symptom of this is itching. Ursodeoxycholic acid is routinely used to treat cholestasis but is not effective in reducing itch in all people who take it. Rifampcin has been used to reduce itch in people with Primary Biliary Cholangitis. This study will randomly allocate women with severe early onset ICP to receive either Ursodeoxycholic Acid, or the "Investigational drug" Rifampicin.

Intervention(s)

Product Name: Rifampicin
Pharmaceutical Form: Film-coated tablet

Product Name: Ursodeoxycholic acid
Pharmaceutical Form: Capsule, hard

Primary Outcome(s)

Secondary Objective: 1. To compare the effect of RIF treatment with UDCA on short-term outcomes for both mother and infant including the length of gestation and the incidence of caesarean section and preterm birth
2. To compare the effect of RIF treatment with UDCA on serum concentrations of: bile acids, transaminases, and on metabolites such as serum autotaxin and progesterone sulphated metabolites, and urine glucuronidated 6a-hydroxylated BA.
3. To assess the effect of RIF and UDCA on the metabolome and the microbiome
4. T o assess the effect of treatment with the RIF compared with UDCA on maternal and fetal outcomes analysed by bile acid transporter genotype.

Primary end point(s): Pruritus, defined as worst itch in the previous 24 hours assessed on a patient-recorded visual analogue scale.

Timepoint(s) of evaluation of this end point: At study entry, one week post randomisation, then monthly up to delivery, with optional assessments on a weekly basis after 28 weeks gestation.

Main Objective: To compare Rifampicin (RIF) with the standard treatment, Ursodeoxycholic acid (UDCA) for the reduction of itch, the main symptom of the disease.

Secondary Outcome(s)

Secondary end point(s): 1. Outcomes for both mother and infant including the length of gestation and the incidence of caesarean section and preterm birth.
2. Serum concentrations of: bile acids, transaminases, and on metabolites such as serum autotaxin and progesterone sulphated metabolites, and urine glucuronidated 6a-hydroxylated BA,
3. Metabolome and the microbiome.
4. Maternal and fetal outcomes analysed by bile acid transporter genotype

Timepoint(s) of evaluation of this end point: These numbers correspond to the secondary outcomes listed in E.5.2 above.
1. assessed at delivery
2. to be assessed at study entry, one week post randomisation then on a monthly basis up to delivery.
3. to be assessed at study entry, one week post randomisation then on a monthly basis up to delivery, one and two weeks post delivery
4. to be assessed once for mother using sample collected at study entry, once for baby using sample collected at birth.

Secondary ID(s)

UofATURRIFIC

ACTRN12618000332224

Source(s) of Monetary Support

Department of Health

Ethics review

Status: Approved
Approval date: 20/05/2020
Contact: