Carvedilol + Simvastatin vs. Carvedilol Alone for Cirrhosis and Cirrhotic Cardiomyopathy and Impact on Hepatic Decompensation and Survival

Sponsor
Post Graduate Institute of Medical Education and Research, Chandigarh
Study ID
NCT06431919
Status
Recruiting
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Conditions

  • Acute Kidney Injury
  • Cirrhosis, Liver
  • Cirrhotic Cardiomyopathy
  • Decompensated Cirrhosis
  • Left Ventricular Diastolic Dysfunction

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Simvastatin 20mg — DRUG
    Simvastatin fixed dose of 20 mg per day
  • Carvedilol 3.125 mg — DRUG
    Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate

Study Details

Cirrhosis and portal hypertension are associated with a hyperdynamic circulation and decompensation events, including development of ascites, variceal bleeding, acute kidney injury, and susceptibility to infections. Rationale: Cirrhosis and portal hypertension are associated with a hyperdynamic circulation and decompensation events, including ascites, variceal bleeding, acute kidney injury, and susceptibility to infections. CCM, present in 30-70% of patients, is characterized by structural and functional abnormalities in the heart, and is associated with progression of cirrhosis, impaired quality of life and poor survival. Statins play a crucial role in reducing proatherogenic LDL cholesterol levels, making them a cornerstone in managing diabetes and cardiovascular diseases (CVDs) with the aim of decreasing or reversing atherosclerosis. This trial aims to evaluate the impact and safety of simvastatin in cirrhotic cardiomyopathy. Novelty: Simvastatin might be of special value in diastolic dysfunction through its hemodynamic and functional effects on LV remodeling and improve portal hemodynamics through the pleotropic effects of lipophilic statins. Objectives: The primary objective is to assess the combined effects of carvedilol and simvastatin in managing CCM vs carvedilol alone for a composite outcome to prevent decompensation and reduce all-cause mortality. We will comprehensively evaluate cardiac function, decompensation events and survival based on impact of simvastatin over the standard betablocker carvedilol. Methods: This is a double-blinded randomized placebo-controlled trial involving patients diagnosed with CCM. Clinical data, including cardiac imaging, cardiac biomarkers, and survival outcomes, will be assessed for either group. Expected Outcome: The investigators anticipate that the synergistic use of simvastatin and carvedilol will effectively reduce portal pressure, improve portal haemodynamic, and enhance cardiac remodelling. Successful reversal of LVDD can potentially prevent clinical events such as ascites, encephalopathy, and acute kidney injury (AKI).

Key Dates

First listed
May 29, 2024
Start date
Jun 10, 2025
Status verified
Jun 2025
Primary completion
Jan 31, 2028
Completion
Feb 29, 2028

Study Design

Enrollment
260 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental: Simvastatin + Carvedilol-arm
    * Simvastatin fixed dose of 20 mg per day * Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate * Standard Medical Therapy
  • Active Comparator: Active Comparator: Carvedilol arm
    * Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate * Standard Medical Therapy

Primary Outcome Measure

Time to acute decompensation event [ Time Frame: 1 Year ]

Central Contacts

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