Effects of Metformin on Portal Hypertension in Cirrhosis Patients
Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension - A Randomized Placebo-controlled Study
This study is testing if metformin can lower blood pressure in the liver for people with cirrhosis and portal hypertension who haven't had enough success with other treatments.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 76 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Locations | 1 site (Clichy, France) |
| Trial ID | NCT06687265 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the impact of metformin on the hepatic venous pressure gradient (HVPG) in patients suffering from cirrhosis and portal hypertension. It is a multicenter, phase II, randomized, placebo-controlled trial that aims to determine whether metformin can effectively reduce HVPG over a 28-day period. The study will include patients who are either non-responders to non-selective beta-blockers or those who require enhanced efficacy in managing their condition. Participants will be randomly assigned to receive either metformin or a placebo.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with a diagnosis of cirrhosis and a high likelihood of having a hepatic venous pressure gradient of 12 mm Hg or higher.
Not a fit: Patients with Child-Pugh class C cirrhosis or those who are not able to provide informed consent may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide a new treatment option for patients with cirrhosis and portal hypertension who do not respond to standard therapies.
How similar studies have performed: Previous studies have shown promising results with metformin in similar patient populations, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Clichy, France
- Facility Name: Beaujon hospital — Clichy, France, France (Recruiting)
Study contacts
- Study coordinator: Lucile Moga
- Email: lucile.moga@aphp.fr
- Phone: 01 71 11 46 69
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.