Effect of Eplerenone on portal pressure in patients with compensated cirrhosis. A randomized placebo-controlled feasibility study.

• Applicant: Professor Dr. Alexander Zipprich
• Subject Area: Gastroenterology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561850000

Our preclinical animal studies suggest that the mineralocorticoid receptor (MR) antagonist Eplerenone may reduce both portal pressure and fibrosis in cirrhosis. The aim of this study is to evaluate whether Eplerenone can lower portal pressure and hepatic fibrosis in patients with compensated cirrhosis and clinically significant portal hypertension. This planned interventional feasibility study will investigate the effects of Eplerenone on portal pressure and hepatic fibrosis in patients with compensated cirrhosis, with a control group receiving a placebo. Participants will include patients with compensated cirrhosis and clinically significant portal hypertension, defined as a hepatic venous pressure gradient (HVPG) of ≥10 mmHg. Key exclusion criteria comprise prior decompensation events (e.g., ascites, hepatic encephalopathy, variceal bleeding), MR antagonist treatment within the last three months, recent dose adjustments of beta-blockers or other vasoactive drugs, treatment with ACE or AT-blockers, and contraindications to MR antagonists (e.g., hyperkalemia or renal insufficiency). The intervention group will receive Eplerenone at a dosage of 50 mg/day over six months, while the control group will receive a placebo. Each patient will be followed up for six months, with portal hypertension and fibrosis degree monitored through invasive and non-invasive methods. The primary endpoint is the reduction of HVPG after six months. Secondary endpoints include reduction of HVPG to below 10 mmHg, a decrease in HVPG by 10%, reduction in fibrosis (assessed through histology and non-invasive techniques), incidence of cirrhosis decompensation, and an increase in PPARα gene expression. The study duration is set at 36 months, including a 24-month recruitment period and a 30-month observation period from the first to the last patient. A total of 24 patients will be included in the final analysis. The planned statistical analysis will follow an intention-to-treat approach. The primary endpoint will be evaluated using a linear regression model adjusted for baseline HVPG, Child-Pugh class, and beta-blocker use. Secondary binary endpoints will be analyzed using logistic regression, and continuous endpoints will also be assessed through regression models. In summary, this feasibility study will evaluate whether Eplerenone may serve as an effective treatment option for reducing portal pressure and fibrosis in compensated cirrhosis. The results are anticipated to contribute to the development of new therapeutic strategies.

• DFG Programme: Clinical Trials
• Co-Investigators: Professorin Dr. Cristina Ripoll; Privatdozentin Dr. Barbara Schreier