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| Name | Class |
|---|---|
| King's College Hospital NHS Trust | OTHER |
| Medway NHS Foundation Trust | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin arm | Active Comparator | Metformin |
|
| Ursodeoxycholic acid | Active Comparator | Ursodeoxycholic acid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Metformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Fetal outcomes | Presence of meconium | Immediately upon delivery date |
| Fetal outcomes | APGAR score at 5 minutes | Immediately upon delivery date |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hassan Shehata, FRCPI, FRCOG | Contact | 01372 735735 | 6887 | hassan.shehata@esth.nhs.uk |
| Amanda Ali, MRCPI, MRCOG | Contact | amandaha.ali@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Hassan Shehata, FRCPI, FRCOG | Epsom & St Helier University Trust | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27824743 | Result | 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. | |
| 32716060 | Derived | 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. |
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| ID | Term |
|---|---|
| D002780 | Cholestasis, Intrahepatic |
| D011248 | Pregnancy Complications |
| ID | Term |
|---|---|
| D002779 | Cholestasis |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| D014580 | Ursodeoxycholic Acid |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D003840 |
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| Ursodeoxycholic Acid | Drug | 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. |
|
|
| 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 |
| Fetal outcomes | Umbilical arterial pH at birth | Immediately upon delivery date |
| Maternal outcomes | Symptoms (itch) - assessed by questionnaire at clinic visits | From date of randomisation to date of delivery assessed up to 26 weeks |
| Maternal outcomes | Maximum dose of medication required | From date of randomisation to date of delivery assessed up to 20 weeks |
| Maternal outcomes | Gestational diabetes | From date of randomisation to date of delivery assessed up to 20 weeks |
| Maternal outcomes | Postpartum haemorrhage | From date of randomisation to date of delivery assessed up to 26 weeks |
| Maternal outcomes | Mode of delivery | From date of randomisation to date of delivery assessed up to 20 weeks |
| Maternal outcomes | Liver failure | From date of randomisation to date of delivery assessed up to 26 weeks |
| D008107 |
| Liver Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| Deoxycholic Acid |
| D002793 | Cholic Acids |
| D001647 | Bile Acids and Salts |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002757 | Cholanes |