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Taking people in FrancePhase 2

Tests metformin in people with cirrhosis and high liver blood pressure

Tests metformin against placebo in adults with cirrhosis and portal hypertension already taking carvedilol.

Key facts

Who runs it
Assistance Publique - Hôpitaux de Paris
Where
Clichy, FranceSee the site
Trial code
Registry title
Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension
Status
Recruiting
Phase
Phase 2
People taking part
76 people, planned
Started
10 Mar 2025
Expected to end
31 Jul 2027
Type of study
Interventional, 2 groupsOne group gets a placebo (a dummy treatment), for comparison.
Treatments tested
  • Metformin
  • Placebo
Record updated
13 April 2025

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with cirrhosis and high pressure in the liver's portal vein who already take carvedilol. It tests metformin against placebo for 28 days.

Age
18 years or older
Sex
Women and men can join.
Disease stage
Cirrhosis, Child-Pugh A or B, with a high likelihood of portal pressure (HVPG) of 12 mm Hg or more. The cause of cirrhosis must be active, or resolved for at least 6 months.
Earlier treatment
Must take carvedilol (6,25 mg/day or more) at a stable dose for at least one month. Cannot be on metformin now or have stopped it less than 3 months ago.
Biomarker or test result
HVPG of 12 mm Hg or more is checked at the first follow-up visit before randomisation.

Main reasons for not taking part

  • Pregnant or breastfeeding women
  • Liver cancer with a nodule over 3 cm (1.2 in) or more than 3 nodules
  • Severe chronic kidney disease (eGFR under 30 mL/min/1,73m2)
  • Complete portal vein thrombosis, TIPS, or liver transplantation in the past
  • Alcohol use over 14 units/week for women or 21 units/week for men

The registry criteria, word for word

Show all 36 criteriaShow less

Who can take part

  • - Age ≥ 18 years
  • Written informed consent to participate in the study
  • Medical insurance coverage
  • For child-bearing aged women, contraception using oestroprogestative, progestative, intrauterine device, or mechanical contraception
  • Diagnosis of cirrhosis based on a liver biopsy, or on clinical, biological, endoscopic, and radiological evidence
  • Active cause of cirrhosis, or resolution (alcohol cessation, sustained virological response to direct-acting antiviral treatment for HCV, initiation of nucleoside/nucleotide analog treatment for HBV) for at least 6 months
  • Child-Pugh A or B
  • High likelihood of HVPG ≥ 12 mm Hg based on investigator's judgement, or on the following criteria:; Investigator's judgement; active cause of cirrhosis and:; History of clinical ascites; Or history of variceal bleeding; Or liver stiffness by VCTE ≥ 35 kPa on carvedilol in the last two years; or spleen stiffness by VCTE ≥ 55 kPa on carvedilol in the last two years; or liver surface nodularity ≥ 2,9 in the last two years; or HVPG \> 16 mm Hg prior to starting NSBB; or Laennec 4c cirrhosis on histology; or resolution of the cause of cirrhosis for at least 6 months and:; history of clinical ascites in the last 6 months; or history of variceal bleeding in the last 6 months; or liver stiffness by VCTE ≥ 35 kPa on carvedilol in the last 6 months; or spleen stiffness by VCTE ≥ 55 kPa on carvedilol in the last 6 months; or liver surface nodularity ≥ 2,9 in the last 12 months; or Laennec 4c cirrhosis on histology in the last 12 months
  • Treatment with carvedilol (≥ 6,25 mg/day) at a stable dose for at least one month
  • Absence of hepatocellular carcinoma outside at least one nodule \> 3 cm in diameter, or more than 3 nodules, on ultrasound, CT-scan or MRI performed during the previous 6 months

Who cannot take part

  • Ongoing treatment with metformin, or discontinued for less than 3 months
  • Treatment with statins started or discontinued for less than 3 months
  • Treatment with nucleoside/nucleotide analogue for HBV, or direct-acting antiviral treatment for HCV, started for less than 6 months
  • Known hypersensitivity to the active substance or any of the excipients
  • History of lactic acidosis, diabetic acidocetosis, or diabetic precoma
  • Ongoing condition that may lead to acute kidney injury or hypoxia: dehydration, severe infection, shock, cardiac decompensation, respiratory failure, or myocardial infarction within the past month
  • Known hypersensitivity to all the iodin-containing contrast agents
  • Known hypersensitivity to lidocaine for local anesthesia
  • Known hypersensitivity to beta-lactam antibiotics if the patient has a history of valve replacement
  • Extra-hepatic cancer without remission
  • Severe chronic kidney disease defined as estimated glomerular filtration rate < 30 mL/min/1,73m2 using the MDRD-6 formula
  • Complete portal vein thrombosis (main portal trunk, or right branch), or portal cavernoma
  • History of TIPS (transjugular intrahepatic portosystemic shunt) / surgical portosystemic derivation / liver transplantation / major hepatectomy
  • Serum total bilirubin > 50 µmol/L
  • Transaminases > 5 ULN
  • Prothrombin ratio < 50 %
  • Need for at least one paracentesis for ascites fluid evacuation in the last 6 months
  • Expected follow-up < 3 months
  • Alcohol consumption > 14 units/week for women or > 21 units/week for men, current or abstinent for less than 6 months
  • Biliary cirrhosis
  • Hepatocellular carcinoma with at least one nodule > 3 cm in diameter, or more than 3 nodules
  • Cholangiocarcinoma
  • Ongoing participation in another interventional therapeutic trial
  • Pregnant or breastfeeding women
  • Patients unable to give consent (under guardianship or curatorship)
  • Non-randomisation criteria: HVPG < 12 mm Hg at the catheterism performed during the first follow-up visit

Where in France

  • Facility Name: Beaujon hospitalClichy, FranceContact: Lucile MOGA, DreTaking people

About the trial

What the trial wants to find out

Portal hypertension (PHT) is defined by an elevated pressure gradient between the portal vein and the hepatic veins ≥ 5 mm Hg, and is the main vector of complications in cirrhosis.

Read full original descriptionShow less

When the hepatic venous pressure gradient (HVPG) is ≥ 10 mm Hg, it is considered as a " clinically significant PHT ": ascites and oesophageal varices (EV) may occur.

Above 12 mm Hg, there is a risk of variceal bleeding. Carvedilol, a non-selective beta-blocker (NSBB), is recommended in all the patients with cirrhosis and clinically significant PHT in order to prevent decompensation of cirrhosis.

Nevertheless, 40 % of patients are NSBB non-responders, i.e. they do not show a significant decrease in HVPG. In addition, NSBB responders treated for primary prophylaxis have an incidence of variceal bleeding of approximately 10% per year, with a six-week mortality of 20%. Therefore, there is an unmet need for PHT in patients with cirrhosis who do not respond to NSBB, and also for an increase in efficacy in responders. In a randomised pilot study, Rittig et al. observed a mean change in HVPG of -2,9 mm Hg in 16 patients with cirrhosis and HVPG ≥ 12 mm Hg, not treated with NSBB, 90 minutes after ingestion of 1000 mg metformin.

The study will be a prospective, national, multicentre, phase II, superiority comparative randomized (1:1) simple-blinded clinical trial with two parallel arms: metformin versus placebo.

The main objective is to evaluate the effect of metformin versus placebo during 28 days on HVPG, in patients with cirrhosis and a HVPG ≥ 12 mm Hg already treated with carvedilol.

Subjects randomized in the metformin group or placebo group will receive metformin ou placebo, one pill of 500 mg per os twice a day (one in the morning and one in the evening, during or at the end of the meal) for 28 days.

The 2 groups in the trial

  • METFORMIN GROUPTreatment being tested

    Treatment: Metformin

  • PLACEBO GROUPPlacebo, for comparison

    Treatment: Placebo

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
Official title
Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension - A Randomized Placebo-controlled Study
Plain-language title
Tests metformin in people with cirrhosis and high liver blood pressureGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Record updated
13 April 2025