Intrahepatic CholestasesPhase 2/3METRICNCT03056274
Metformin in Intrahepatic Cholestasis of Pregnancy
A Phase 2/3 study testing Metformin and Ursodeoxycholic Acid in people with Intrahepatic Cholestases and Pregnancy Complications, run by Epsom and St Helier University Hospitals NHS Trust.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Intrahepatic Cholestases, Pregnancy Complications
- What is being tested?
- Metformin and Ursodeoxycholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Jan 2019to Sep 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
Amanda Ali, MRCPI, MRCOG contact
About this study
Official title: METformin in Intrahepatic Cholestasis of Pregnancy (METRIC) Study
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.
Read the 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.
- Conditions
- Intrahepatic Cholestases, Pregnancy Complications
- Being tested
- Metformin, Ursodeoxycholic Acid
- Keywords
- Metformin, Ursodeoxycholic acid, Outcomes
- Medical subject headings
- Cholestasis, Intrahepatic, Pregnancy Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Metformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes
Ursodeoxycholic AcidDrug
Also called Destolit®, Urdox®, Ursofalk®, Ursogal®
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin arm | Active comparator | Metformin Receives: Drug: Ursodeoxycholic Acid |
| Ursodeoxycholic acid | Active comparator | Ursodeoxycholic acid Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: From date of randomisation to date of delivery assessed up to 26 weeks
Secondary outcomes (6)
Fetal outcomes
Perinatal death
Measured: From date of randomisation to date of delivery assessed up to 26 weeks
Fetal outcomes
Preterm delivery
Measured: From date of randomisation to date of delivery assessed up to 26 weeks
Fetal outcomes
Respiratory distress syndrome
Measured: Immediately upon delivery date
Fetal outcomes
Birth weight (g)
Measured: Immediately upon delivery date
Fetal outcomes
Birth weight percentile
Measured: Immediately upon delivery date
Fetal outcomes
Gestational age at delivery
Measured: Immediately upon delivery date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2017
- Study startJan 2019 (estimated)
- Primary completionJun 2019 (estimated)
- Study completionSep 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intrahepatic CholestasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Epsom and St Helier University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College Hospital NHS Trust, Medway NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Hassan Shehata, FRCPI, FRCOG, Principal investigator, Epsom & St Helier University Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056274
- Sponsor's protocol ID
- RVR
- Acronym
- METRIC
- Status last verified
- Jan 2018
- First submitted
- 22 Dec 2016
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27824743Walker 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.
PubMed 32716060
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- METformin in Intrahepatic Cholestasis of Pregnancy (METRIC) Study
- ClinicalTrials.gov ID
- NCT03056274
- Acronym / sponsor ID
- METRIC / RVR
- Conditions
- Intrahepatic Cholestases, Pregnancy Complications
- Keywords
- Metformin, Ursodeoxycholic acid, Outcomes
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Epsom and St Helier University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- King's College Hospital NHS Trust, Medway NHS Foundation Trust
- Study start
- Jan 2019 (estimated)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Sep 2019 (estimated)
- First posted
- 17 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin arm | Active comparator | Drug: Ursodeoxycholic AcidMetformin |
| Ursodeoxycholic acid | Active comparator | Drug: MetforminUrsodeoxycholic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageMetformin Hydrochloride (HCl) Tablets, is an oral antihyperglycemic drug used in the management of type 2 diabetes | Drug | Ursodeoxycholic acid |
| Ursodeoxycholic AcidAlso: Destolit®, Urdox®, Ursofalk®, Ursogal®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. | Drug | Metformin arm |
Primary outcome
Normalisation of maternal serum concentration of bile salts and liver enzymes
Time frame: 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
Time frame: 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
6 secondary outcomes
Fetal outcomes
Time frame: From date of randomisation to date of delivery assessed up to 26 weeks
Fetal outcomes
Time frame: From date of randomisation to date of delivery assessed up to 26 weeks
Fetal outcomes
Time frame: Immediately upon delivery date
Fetal outcomes
Time frame: Immediately upon delivery date
Fetal outcomes
Time frame: Immediately upon delivery date
Fetal outcomes
Time frame: Immediately upon delivery date
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- Results publication: PubMed 27824743Elfituri A, Ali A, Shehata H. Managing Recurring Obstetric Cholestasis With Metformin. Obstet Gynecol. 2016 Dec;128(6):1320-1323. doi: 10.1097/AOG.0000000000001748.
- Derived from this study: PubMed 32716060Walker 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amanda Ali, MRCPI, MRCOG contact
Hassan Shehata, FRCPI, FRCOG principal investigator
Epsom & St Helier University Trust
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Metformin and Ursodeoxycholic Acid in people with Intrahepatic Cholestases and Pregnancy Complications, run by Epsom and St Helier University Hospitals NHS Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hassan Shehata, FRCPI, FRCOG (01372 735735 ext. 6887, hassan.shehata@esth.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normalisation of maternal serum concentration of bile salts and liver enzymes (time frame: From date of randomisation to date of delivery assessed up to 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03056274, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2018.