|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|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.
|Medical condition in easily understood language
|ICP is a liver condition in pregnancy where women develop severe itching and high concentration of bile acid in their blood. ICP is associated with increased risk of premature delivery and stillbirth.
|Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To compare Rifampicin (RIF) with the standard treatment, Ursodeoxycholic acid (UDCA) for the reduction of itch, the main symptom of the disease.
|Secondary objectives of the trial
|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 6α-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.
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|The sub-studies are fully described in the Protocol Version 5, 27 March 2019. The sub-studies cover the analysis of the serum, urine, microbiome, metabolome and genetic samples collected. These are:
TURRIFIC tests - Biochemical and microbiological assessments
TURRIFIC genes - Genetic and virome assessments
Objectives as in E.2.2 above
|Principal 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
|Principal 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 α-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
|E.5 End points
|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.
|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 6α-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.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|End of trial will be at data base lock. This is so that any "data cleaning" and queries may be completed.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months