Clinical trial NCT03056274: Metformin in Intrahepatic Cholestasis of Pregnancy
Official title: METformin in Intrahepatic Cholestasis of Pregnancy (METRIC) Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Intrahepatic Cholestases
Pregnancy Complications
Keywords: Metformin
Ursodeoxycholic acid
Outcomes
Lead sponsor: Epsom and St Helier University Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: King's College Hospital NHS Trust
name: Medway NHS Foundation Trust
First posted: 2017-02-17
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pilot study aimed at comparing the effect of metformin versus ursodeoxycholic acid in women with intrahepatic cholestasis in pregnancy. The study will be conducted in three NHS hospital sites, over an 18 month period.

Detailed description: Intrahepatic cholestasis is a condition that affects pregnant women. It is characterised by itching, usually in the third trimester of pregnancy and is associated with an increase in the liver enzymes and bile salts. This can be associated with maternal and neonatal morbidity, and rarely perinatal mortality.

The investigators propose to assess and compare the effect of Metformin versus Ursodeoxycholic acid on lowering liver enzymes and bile salts, improving maternal morbidity and improving neonatal outcomes.

This study is a pilot study that will be conducted at 3 NHS hospital sites where patients will randomly assigned to receive either Metformin or Ursodeoxycholic acid. There will be 20 patient in each arm. Recruitment will commence in February 2017 and will run for an 18 month period.

Eligibility criteria: Inclusion Criteria:

1. 20+0 to 40 weeks' gestation on day of randomisation
2. Itching with a raised serum bile acid above the upper limit of normal
3. Normal anomaly scan at 20 weeks
4. Aged 18 years or over
5. Able to give written informed consent
6. No known pre-existing liver disease

Exclusion Criteria:

1. Decision already made for delivery within the next 48 hours
2. Known allergy to any component of the ursodeoxycholic acid or metformin tablets
3. Patients already on metformin for other conditions

Primary outcomes:
measure: Normalisation of maternal serum concentration of bile salts and liver enzymes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
measure: Normalisation of maternal serum concentration of liver enzymes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
Secondary outcomes:
measure: Fetal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
measure: Fetal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
Other outcomes:
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
measure: Fetal outcomes
timeFrame: Immediately upon delivery date
measure: Maternal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
measure: Maternal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 20 weeks
measure: Maternal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 20 weeks
measure: Maternal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
measure: Maternal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 20 weeks
measure: Maternal outcomes
timeFrame: From date of randomisation to date of delivery assessed up to 26 weeks
Locations:
Study officials:
affiliation: Epsom & St Helier University Trust
name: Hassan Shehata, FRCPI, FRCOG
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elfituri A, Ali A, Shehata H. Managing Recurring Obstetric Cholestasis With Metformin. Obstet Gynecol. 2016 Dec;128(6):1320-1323. doi: 10.1097/AOG.0000000000001748.
citation: Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev. 2020 Jul 27;7(7):CD000493. doi: 10.1002/14651858.CD000493.pub3.