Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Nov 12, 2024

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a medication called metformin on patients with cirrhosis (a serious liver condition) and portal hypertension (high blood pressure in the liver). The trial aims to see if metformin can lower the pressure in the liver's blood vessels more effectively than a placebo (a sugar pill) over a period of 28 days. Participants will be adults aged 18 and older who have been diagnosed with cirrhosis and are already taking a medication called carvedilol to manage their condition. Eligible participants must have a specific level of high blood pressure in their liver (known as hepatic venous pressure gradient or HVPG) and meet certain health criteria.

If you join the trial, you will take one pill of either metformin or a placebo twice a day for 28 days. The study is important because many patients with cirrhosis do not respond well to standard treatments, and there is a need for better options. The trial is currently recruiting participants, and everyone involved will be monitored carefully to ensure their safety.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • - 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:
• • 1. Investigator's judgement
• 2. 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
• 3. 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
• Exclusion Criteria:
• • Serum total bilirubin \> 50 µmol/L
• • Prothrombin ratio \< 50 %
• • Transaminases \> 5 ULN
• • Need for at least one paracentesis for ascites fluid evacuation in the last 6 months
• • Expected follow-up \< 3 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
• • 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
• • 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
• • 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
• • 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
• • 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