Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension
Status:
RECRUITING
Trial end date:
2027-07-31
Target enrollment:
Participant gender:
Summary
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.
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.