Metformin in Intrahepatic Cholestasis of Pregnancy

Pregnancy Complications Clinical Trial

— METRIC  

Official title:

METformin in Intrahepatic Cholestasis of Pregnancy (METRIC) Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03056274
• Other study ID #: RVR
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: January 2019
• Est. completion date: September 2019

Study information

• Verified date: January 2018
• Source: Epsom and St Helier University Hospitals NHS Trust
• Contact: Hassan Shehata, FRCPI, FRCOG
• Phone: 01372 735735
• Email: hassan.shehata[@]esth.nhs.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: September 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholestasis
• Cholestasis, Intrahepatic
• Intrahepatic Cholestases
• Pregnancy Complications

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Epsom and St Helier University Hospitals NHS Trust	King's College Hospital NHS Trust, Medway NHS Foundation Trust

References & Publications (1)

Elfituri A, Ali A, Shehata H. Managing Recurring Obstetric Cholestasis With Metformin. Obstet Gynecol. 2016 Dec;128(6):1320-1323. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fetal outcomes	Presence of meconium	Immediately upon delivery date
Other	Fetal outcomes	APGAR score at 5 minutes	Immediately upon delivery date
Other	Fetal outcomes	Umbilical arterial pH at birth	Immediately upon delivery date
Other	Maternal outcomes	Symptoms (itch) - assessed by questionnaire at clinic visits	From date of randomisation to date of delivery assessed up to 26 weeks
Other	Maternal outcomes	Maximum dose of medication required	From date of randomisation to date of delivery assessed up to 20 weeks
Other	Maternal outcomes	Gestational diabetes	From date of randomisation to date of delivery assessed up to 20 weeks
Other	Maternal outcomes	Postpartum haemorrhage	From date of randomisation to date of delivery assessed up to 26 weeks
Other	Maternal outcomes	Mode of delivery	From date of randomisation to date of delivery assessed up to 20 weeks
Other	Maternal outcomes	Liver failure	From date of randomisation to date of delivery assessed up to 26 weeks
Primary	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
Primary	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	Fetal outcomes	Perinatal death	From date of randomisation to date of delivery assessed up to 26 weeks
Secondary	Fetal outcomes	Preterm delivery	From date of randomisation to date of delivery assessed up to 26 weeks
Secondary	Fetal outcomes	Respiratory distress syndrome	Immediately upon delivery date
Secondary	Fetal outcomes	Birth weight (g)	Immediately upon delivery date
Secondary	Fetal outcomes	Birth weight percentile	Immediately upon delivery date
Secondary	Fetal outcomes	Gestational age at delivery	Immediately upon delivery date