METRIC: Metformin in Intrahepatic Cholestasis of Pregnancy

Sponsor

Epsom and St Helier University Hospitals NHS Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT03056274

Collaborator

King's College Hospital NHS Trust (Other), Medway NHS Foundation Trust (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intrahepatic Cholestases Pregnancy Complications	Drug: Metformin Drug: Ursodeoxycholic Acid	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

METformin in Intrahepatic Cholestasis of Pregnancy (METRIC) Study

Anticipated Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Jun 1, 2019

Anticipated Study Completion Date :

Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metformin arm Metformin	Drug: Ursodeoxycholic Acid 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. Other Names: Destolit®, Urdox®, Ursofalk®, Ursogal®
Active Comparator: Ursodeoxycholic acid Ursodeoxycholic acid	Drug: Metformin Metformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes Other Names: Glucophage

Arm

Intervention/Treatment

Active Comparator: Metformin arm

Metformin

Drug: Ursodeoxycholic Acid

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.

Other Names:

Destolit®, Urdox®, Ursofalk®, Ursogal®

Active Comparator: Ursodeoxycholic acid

Ursodeoxycholic acid

Drug: Metformin

Metformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes

Other Names:

Glucophage

Outcome Measures

Primary Outcome Measures

Normalisation of maternal serum concentration of bile salts and liver enzymes [From date of randomisation to date of delivery assessed up to 26 weeks]
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
Normalisation of maternal serum concentration of liver enzymes [From date of randomisation to date of delivery assessed up to 26 weeks]
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

Secondary Outcome Measures

Fetal outcomes [From date of randomisation to date of delivery assessed up to 26 weeks]
Perinatal death
Fetal outcomes [From date of randomisation to date of delivery assessed up to 26 weeks]
Preterm delivery
Fetal outcomes [Immediately upon delivery date]
Respiratory distress syndrome
Fetal outcomes [Immediately upon delivery date]
Birth weight (g)
Fetal outcomes [Immediately upon delivery date]
Birth weight percentile
Fetal outcomes [Immediately upon delivery date]
Gestational age at delivery

Other Outcome Measures

Fetal outcomes [Immediately upon delivery date]
Presence of meconium
Fetal outcomes [Immediately upon delivery date]
APGAR score at 5 minutes
Fetal outcomes [Immediately upon delivery date]
Umbilical arterial pH at birth
Maternal outcomes [From date of randomisation to date of delivery assessed up to 26 weeks]
Symptoms (itch) - assessed by questionnaire at clinic visits
Maternal outcomes [From date of randomisation to date of delivery assessed up to 20 weeks]
Maximum dose of medication required
Maternal outcomes [From date of randomisation to date of delivery assessed up to 20 weeks]
Gestational diabetes
Maternal outcomes [From date of randomisation to date of delivery assessed up to 26 weeks]
Postpartum haemorrhage
Maternal outcomes [From date of randomisation to date of delivery assessed up to 20 weeks]
Mode of delivery
Maternal outcomes [From date of randomisation to date of delivery assessed up to 26 weeks]
Liver failure