Decompensated CirrhosisCIRROSTATNCT06431919
Carvedilol + Simvastatin vs. Carvedilol Alone for Cirrhosis and Cirrhotic Cardiomyopathy and Impact on Hepatic Decompensation and Survival
A study testing Simvastatin 20mg and Carvedilol 3.125 mg in people with Decompensated Cirrhosis and Cirrhotic Cardiomyopathy, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Decompensated Cirrhosis, Cirrhotic Cardiomyopathy, Cirrhosis, Liver
- What is being tested?
- Simvastatin 20mg and Carvedilol 3.125 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 1 siteIndia
- Study dates
- 10 Jun 2025to Feb 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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.)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 recruiting
- Recruiting
PGIMER, Department of Hepatology
Chandigarh, 160012
Prerna Sharma, MSc, +911722754777, hepatology.mpk@gmail.com
About this study
Official title: 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
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:
Read more
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).
Read the detailed description
Cirrhotic cardiomyopathy (CCM) in chronic liver disease is seen as a blunted contractile responsiveness to stress, and/or altered diastolic relaxation with electrophysiological abnormalities, in absence of known cardiac disease. Cirrhosis induces systemic inflammation, and oxidative stress leading to cardiac structural remodeling, including fibrosis, hypertrophy, and chamber dilation. CCM is associated with risk of LVDD which further lead to hepatorenal syndrome (HRS), septic shock. and peri transplant cardiac complications. Autonomic dysfunction, and neurohormonal imbalances, cardiac arrhythmias, overt heart failure are common features of CCM in advanced liver disease. Efforts to ameliorate the abnormalities associated with CCM are crucial and necessitate a significant evidence-based therapeutic intervention. We have tested the use of carvedilol in this population and found that it causes an improvement in survival.
CCM can be managed by reducing preload (though nitrates), and by ameliorating neurohormonal activation. Lowering the heart rate to 55-65 beats per minute (bpm), as done with β-blockers, is likely to help by improving myocardial oxygen demand and coronary perfusion time with independent effects on portal hypertension, and heart failure. β-blockers may reduce myocardial contractility and patients with cirrhosis have low tolerance to β-blocker dosages required to achieve a THR of 55-65 bpm. Ivabradine is useful in a subset with baseline tachycardia but does not offer survival benefit over carvedilol alone. Therefore, there is a great need to evaluate other agents that can achieve improvement in CCM related complications in cirrhosis.
- Furthermore, β-blockers might diminish myocardial contractility, and patients with cirrhosis may struggle to tolerate β-blocker doses necessary for attaining a target heart rate (THR) of 55-65 bpm. Hence, there's a critical necessity to assess alternative agents capable of ameliorating complications associated with cirrhotic cardiomyopathy (CCM).
- Early interventions to avert cardiovascular morbidity will prove to be cost effective in managing outcome, as they avert high cost of managing the public health burden of all-cause mortality in cirrhosis.
- Cardiovascular complications stand as the primary cause of mortality post-liver transplantation (LT), underscoring the need for thorough evaluation before LT.
- This study will systematically screen participants for coronary artery disease as an integral part of its screening process.
- Statins, particularly simvastatin, exert a favorable impact on vascular reactivity especially in cirrhosis. Simvastatin increases the production of nitric oxide(NO), leading to increased hepatic blood flow and reduced sinusoidal resistance, particularly upon short-term exposure. resistance.
- Simvastatin has an acceptable adverse event profile in decompensated Child B patients. There is no high-quality evidence specifically evaluating the role of simvastatin in cirrhotic cardiomyopathy, although there are data to suggest its efficacy in portal hypertension. The proposed project covers an area of overlap between cardiovascular and liver disease outcomes, which reflect as decompensation events, worsening in liver severity scores and all-cause mortality.
- Conditions
- Decompensated Cirrhosis, Cirrhotic Cardiomyopathy, Cirrhosis, Liver, Left Ventricular Diastolic Dysfunction, Acute Kidney Injury
- Being tested
- Simvastatin 20mg, Carvedilol 3.125 mg
- Keywords
- Decompensated Cirrhosis, Cirrhotic Cardiomyopathy, Left ventricular diastolic dysfunction, Acute kidney injury
- Medical subject headings
- Liver Cirrhosis, Ventricular Dysfunction, Left, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 20mgDrug
Simvastatin fixed dose of 20 mg per day
Carvedilol 3.125 mgDrug
Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Simvastatin + Carvedilol-arm | Experimental | * 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 Receives: Drug: Simvastatin 20mg; Drug: Carvedilol 3.125 mg |
| Active Comparator: Carvedilol arm | Active comparator | * Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate
* Standard Medical Therapy Receives: Drug: Carvedilol 3.125 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to acute decompensation event
The primary outcome measure is defined as a composite end point of acute decompensation event (acute variceal bleeding, new ascites or recurrence of previously controlled ascites, episode of hepatic encephalopathy or acute kidney injury) OR all-cause death in patients with cirrhosis and cirrhotic cardiomyopathy
Measured: 1 Year
Secondary outcomes (5)
All-cause Mortality
Measured: From enrollment until 1 year of follow up
Any New decompensation event
New decompensation events are defined as decompensation event( ascites, hepatic encephalopathy, variceal bleeding) in a previously compensated patient with cirrhosis or further decompensation when a new event [recurrence of ascites, hepatorenal syndrome-acute kidney injury (HRS-AKI), hepatic encephalopathy (HE), or acute variceal bleeding (AVB), spontaneous bacterial peritonitis (SBP)] occurs in a patient with previously decompensated disease
Measured: 1 Year
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging
Measured: 1 Year
Episodes warranting hospitalization
Number of hospital admissions on follow up.
Measured: 1 Year
Serum level of BNP and other cardiac and inflammatory biomarkers
ELISA or autoanalyzer will be performed for qunatification
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2024
- Study start10 Jun 2025 (estimated)
- Primary completion31 Jan 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Decompensated CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Collaborators
- Indian Council of Medical Research
- Responsible party
- Principal investigator, Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Dr Madhumita Premkumar, DM, Principal investigator, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06431919
- Sponsor's protocol ID
- PGI/HEP/000214
- Other IDs
- IIRPSG-2024-01-02107
- Acronym
- CIRROSTAT
- Status last verified
- Jun 2025
- First submitted
- 22 May 2024
- Last updated
- 8 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06431919
- Acronym / sponsor ID
- CIRROSTAT / PGI/HEP/000214
- Conditions
- Decompensated Cirrhosis, Cirrhotic Cardiomyopathy, Cirrhosis, Liver, Left Ventricular Diastolic Dysfunction, Acute Kidney Injury
- Keywords
- Decompensated Cirrhosis, Cirrhotic Cardiomyopathy, Left ventricular diastolic dysfunction, Acute kidney injury
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Collaborators
- Indian Council of Medical Research
- Study start
- 10 Jun 2025 (estimated)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 29 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Cirrhotic cardiomyopathy (CCM) in chronic liver disease is seen as a blunted contractile responsiveness to stress, and/or altered diastolic relaxation with electrophysiological abnormalities, in absence of known cardiac disease. Cirrhosis induces systemic inflammation, and oxidative stress leading to cardiac structural remodeling, including fibrosis, hypertrophy, and chamber dilation. CCM is associated with risk of LVDD which further lead to hepatorenal syndrome (HRS), septic shock. and peri transplant cardiac complications. Autonomic dysfunction, and neurohormonal imbalances, cardiac arrhythmias, overt heart failure are common features of CCM in advanced liver disease. Efforts to ameliorate the abnormalities associated with CCM are crucial and necessitate a significant evidence-based therapeutic intervention. We have tested the use of carvedilol in this population and found that it causes an improvement in survival.
CCM can be managed by reducing preload (though nitrates), and by ameliorating neurohormonal activation. Lowering the heart rate to 55-65 beats per minute (bpm), as done with β-blockers, is likely to help by improving myocardial oxygen demand and coronary perfusion time with independent effects on portal hypertension, and heart failure. β-blockers may reduce myocardial contractility and patients with cirrhosis have low tolerance to β-blocker dosages required to achieve a THR of 55-65 bpm. Ivabradine is useful in a subset with baseline tachycardia but does not offer survival benefit over carvedilol alone. Therefore, there is a great need to evaluate other agents that can achieve improvement in CCM related complications in cirrhosis.
- Furthermore, β-blockers might diminish myocardial contractility, and patients with cirrhosis may struggle to tolerate β-blocker doses necessary for attaining a target heart rate (THR) of 55-65 bpm. Hence, there's a critical necessity to assess alternative agents capable of ameliorating complications associated with cirrhotic cardiomyopathy (CCM).
- Early interventions to avert cardiovascular morbidity will prove to be cost effective in managing outcome, as they avert high cost of managing the public health burden of all-cause mortality in cirrhosis.
- Cardiovascular complications stand as the primary cause of mortality post-liver transplantation (LT), underscoring the need for thorough evaluation before LT.
- This study will systematically screen participants for coronary artery disease as an integral part of its screening process.
- Statins, particularly simvastatin, exert a favorable impact on vascular reactivity especially in cirrhosis. Simvastatin increases the production of nitric oxide(NO), leading to increased hepatic blood flow and reduced sinusoidal resistance, particularly upon short-term exposure. resistance.
- Simvastatin has an acceptable adverse event profile in decompensated Child B patients. There is no high-quality evidence specifically evaluating the role of simvastatin in cirrhotic cardiomyopathy, although there are data to suggest its efficacy in portal hypertension. The proposed project covers an area of overlap between cardiovascular and liver disease outcomes, which reflect as decompensation events, worsening in liver severity scores and all-cause mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: Simvastatin + Carvedilol-arm | Experimental | Drug: Simvastatin 20mg, Drug: Carvedilol 3.125 mg* 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: Carvedilol arm | Active comparator | Drug: Carvedilol 3.125 mg* Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate * Standard Medical Therapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin 20mgSimvastatin fixed dose of 20 mg per day | Drug | Experimental: Simvastatin + Carvedilol-arm |
| Carvedilol 3.125 mgCarvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate | Drug | Active Comparator: Carvedilol arm, Experimental: Simvastatin + Carvedilol-arm |
Primary outcome
Time to acute decompensation event
Time frame: 1 Year
The primary outcome measure is defined as a composite end point of acute decompensation event (acute variceal bleeding, new ascites or recurrence of previously controlled ascites, episode of hepatic encephalopathy or acute kidney injury) OR all-cause death in patients with cirrhosis and cirrhotic cardiomyopathy
5 secondary outcomes
All-cause Mortality
Time frame: From enrollment until 1 year of follow up
Any New decompensation event
Time frame: 1 Year
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging
Time frame: 1 Year
Episodes warranting hospitalization
Time frame: 1 Year
Serum level of BNP and other cardiac and inflammatory biomarkers
Time frame: 1 Year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr Madhumita Premkumar, DM principal investigator
Post Graduate Institute of Medical Education and Research, Chandigarh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Simvastatin 20mg and Carvedilol 3.125 mg in people with Decompensated Cirrhosis and Cirrhotic Cardiomyopathy, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr Madhumita Premkumar, DM (7087003409, drmadhumitap@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to acute decompensation event (time frame: 1 Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2025.