Intrahepatic Cholestases, Pregnancy Complications
Conditions
Keywords
Metformin, Ursodeoxycholic acid, Outcomes
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.
Interventions
DRUGMetformin
Metformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes
DRUGUrsodeoxycholic 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.
Sponsors
King's College Hospital NHS Trust
Medway NHS Foundation Trust
Epsom and St Helier University Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Fetal outcomes | From date of randomisation to date of delivery assessed up to 26 weeks | Perinatal death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Fetal outcomes | Immediately upon delivery date | Presence of meconium |
| Maternal outcomes | From date of randomisation to date of delivery assessed up to 26 weeks | Symptoms (itch) - assessed by questionnaire at clinic visits |
Contacts
Primary ContactHassan Shehata, FRCPI, FRCOG
Backup ContactAmanda Ali, MRCPI, MRCOG
Outcome results
None listed