Metformin in Intrahepatic Cholestasis of Pregnancy

Study Overview
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Brief Summary
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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
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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.

Official Title
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METformin in Intrahepatic Cholestasis of Pregnancy (METRIC) Study

Conditions
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Intrahepatic Cholestases, Pregnancy Complications

Intervention / Treatment
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* Drug: Metformin
* Drug: Ursodeoxycholic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20+0 to 40 weeks' gestation on day of randomisation Itching with a raised serum bile acid above the upper limit of normal Normal anomaly scan at 20 weeks Aged 18 years or over Able to give written informed consent No known pre-existing liver disease Exclusion Criteria: Decision already made for delivery within the next 48 hours Known allergy to any component of the ursodeoxycholic acid or metformin tablets Patients already on metformin for other conditions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin arm<br>Metformin | Drug: Ursodeoxycholic Acid<br>* Ursodeoxycholic acid (UDCA) is used to treat gallstones and primary biliary cirrhosis. UDCA is also used to treat obstetric cholestasis (OC), a liver condition that occurs specifically in pregnancy.<br>* Other names: Destolit®, Urdox®, Ursofalk®, Ursogal®;|
| Active Comparator: Ursodeoxycholic acid<br>Ursodeoxycholic acid | Drug: Metformin<br>* Metformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes<br>* Other names: Glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalisation of maternal serum concentration of bile salts and liver enzymes | Normalisation of Bile acids and liver enzymes - both parameters are the cornerstone for a diagnosis of intrahepatic cholestasis. They have been separated into two outcomes due to to the different laboratory indices of measurement. Results will be aggregated together to report number of patients with abnormal results | From date of randomisation to date of delivery assessed up to 26 weeks | 
| Normalisation of maternal serum concentration of liver enzymes | Normalisation of liver enzymes Alanine transaminase Aspartate transaminase Bilirubin (total) Gamma glutamyl transferase Results will be aggregated together to report the number of patients with abnormal liver enzymes | From date of randomisation to date of delivery assessed up to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal outcomes | Perinatal death | From date of randomisation to date of delivery assessed up to 26 weeks | 
| Fetal outcomes | Preterm delivery | From date of randomisation to date of delivery assessed up to 26 weeks | 
| Fetal outcomes | Respiratory distress syndrome | Immediately upon delivery date | 
| Fetal outcomes | Birth weight (g) | Immediately upon delivery date | 
| Fetal outcomes | Birth weight percentile | Immediately upon delivery date | 
| Fetal outcomes | Gestational age at delivery | Immediately upon delivery date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Ursodeoxycholic acid, Outcomes