Carvedilol plus simvastatin versus carvedilol alone for cirrhosis-related heart dysfunction

Carvedilol + Simvastatin vs. Carvedilol Alone for Chronic Liver Disease and Cirrhotic Cardiomyopathy and Its Impact on Hepatic Decompensation and Survival; a Double-blind Randomized Controlled Trial

This trial will test whether adding simvastatin to carvedilol helps adults with cirrhosis and cirrhotic cardiomyopathy reduce liver decompensation and improve survival.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 260 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh (Academic / other)
• Locations: 1 site (Chandigarh)
• Trial ID: NCT06431919 on ClinicalTrials.gov

What this trial studies

This is a randomized interventional comparison of carvedilol alone versus carvedilol plus simvastatin 20 mg in adults 18–65 with compensated cirrhosis and cirrhotic cardiomyopathy (EF >50%) conducted at PGIMER Chandigarh. Participants receive carvedilol (3.125 mg) with or without simvastatin and are followed for hepatic decompensation events, cardiac function, renal outcomes, adverse effects, and survival. Major exclusions include advanced cirrhosis (Child-Pugh >9), significant renal dysfunction, recent statin use, coronary artery disease, and other contraindications to statins. The trial emphasizes clinical endpoints (decompensation and survival) and safety monitoring of statin therapy in chronic liver disease.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–65 with compensated cirrhosis and echocardiographic evidence of cirrhotic cardiomyopathy (EF >50%) who are not on recent statin therapy and have no major cardiac disease or severe renal impairment.

Not a fit: Patients with advanced liver disease (Child-Pugh >9), active hepatocellular carcinoma, recent major variceal bleeding, significant renal failure, pregnancy, or contraindications to statins are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, adding simvastatin could lower rates of ascites, variceal bleeding, acute kidney injury, and improve survival in patients with cirrhosis and cirrhotic cardiomyopathy.

How similar studies have performed: Carvedilol has prior evidence of survival benefit in this population and statins have shown promising signals in other cirrhosis settings, but simvastatin specifically for cirrhotic cardiomyopathy is relatively untested.

Eligibility criteria

Inclusion Criteria:

* Age range of 18-65 years
* Compensated cirrhosis, as diagnosed by histology or clinical, laboratory and USG findings,
* CCM (with EF\>50%) on 2D echocardiography with TDI
* Written informed consent.

Exclusion Criteria:

* Age \>65 years
* Serum Creatinine\>2 mg/dl
* Patient previously treated with statin (one month before the study)
* Contraindications to statins
* Advanced Cirrhosis (CTP score\>9)
* Coronary artery disease
* Sick sinus syndrome/ Pacemaker, valvular heart disease
* Cardiac rhythm disorder, Peripartum cardiomyopathy
* Portopulmonary hypertension/ hepatopulmonary syndrome
* Transjugular intrahepatic portosystemic shunt (TIPS) insertion
* Hepatocellular carcinoma
* Pregnancy or lactation
* Patients with HIV or retroviral therapy
* Anemia Hb \< 8gm/dl in females, and \< 9 gm/dl in males
* Acute variceal bleeding in last 6 months.
* Need for medications, metabolized by CYP3A4(such as amlodipine, verapamil, fenofibrate azole antibiotics, protease inhibitors etc.)

Where this trial is running

Chandigarh

• PGIMER, Department of Hepatology — Chandigarh, India (Recruiting)

Study contacts

• Principal investigator: Dr Madhumita Premkumar, DM — Post Graduate Institute of Medical Education and Research, Chandigarh
• Study coordinator: Dr Madhumita Premkumar, DM

Conditions Decompensated Cirrhosis; Cirrhotic Cardiomyopathy; Cirrhosis, Liver; Left Ventricular Diastolic Dysfunction; Acute Kidney Injury; Left ventricular diastolic dysfunction; Acute kidney injury