Cirrhotic CardiomyopathyPhase 4DICENCT07322237
DICE Study- Diastolic Improvement With Carvedilol & Empagliflozin in Patients With Cirrhosis
A Phase 4 study testing Empagliflozin + Carvedilol and Carvedilol in people with Cirrhotic Cardiomyopathy and Empagliflozin, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
1. This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cirrhotic Cardiomyopathy, Empagliflozin, Cardiometabolic Risk Factors
- What is being tested?
- Empagliflozin + Carvedilol and Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteIndia
- Study dates
- 1 Apr 2026to 30 Jun 2029
- Phase
- Phase 4
- 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
- Cirrhosis as diagnosed by histology or clinical laboratory and USG findings
- LVDD (with EF>50%) on 2D echocardiography with TDI
- Written informed consent.
Who cannot join
- Age >65 years
- Serum Creatinine>2 mg/dl
- History of urinary tract /genital infections in last 3 months
- Patient on treatment with statin (one month before the study)
- Advanced Cirrhosis (MELD>20)
- Coronary artery disease
Show all 15Show fewer
- Sick sinus syndrome/ Pacemaker valvular heart disease
- Cardiac rhythm disorder Peripartum cardiomyopathy
- Portopulmonary hypertension/ hepatopulmonary syndrome
- Transjugular intrahepatic porto systemic 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 6months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Madumita Premkumar contact
India1 site, 1 recruiting
- Recruiting
PGIMER Chandigarh
Chandigarh, 160012
Prerna Sharma, 01722754777, hepatology.mpk@gmail.com
About this study
Official title: Empagliflozin + Carvedilol vs. Carvedilol Alone for Patients With Cirrhosis and Left Ventricular Diastolic Dysfunction and Impact on Hepatic Decompensation and Survival: A Double-Blind Placebo-Controlled Randomized Controlled Trial
- This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. The drug has been found to be useful in large trials on heart failure with preserved ejection fraction in the general population with improvement in MASLD progression, with improvement in body weight and hepatic steatosis but no change in liver fibrosis.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the development and progression of heart failure in patients with type 2 diabetes and in those with heart failure and a reduced and preserved ejection fraction. In patients with cirrhosis safety of empagliflozin in a dose of 10 mg has been demonstrated.
- Prevention of decompensation related events in cirrhosis is the key endpoint of any liver-directed therapy as the median survival in the compensated state exceeds 10 years but median survival in the decompensated state approximates 1.5 years. Previous data has demonstrated the risk of hepatic decompensation acute kidney injury and poor survival in patients with cirrhosis and heart failure with preserved ejection fraction (HFpEF) i.e. LVDD a large subset of whom meet criteria for CCM.
Read the detailed description
New diagnostic criteria for cirrhotic cardiomyopathy For the diagnosis of cirrhotic cardiomyopathy (CCM) we will use criteria proposed by the CCM consortium in 2020 with modification to take septal e' and E/e' readings. In accordance with the recent CCM criteria 'systolic dysfunction is defined as an ejection fraction (EF) of 50% or less or an absolute value of GLS <18%. LVDD grade will be determined if 3 of the following 4 criteria are met: early diastolic trans mitral flow to early diastolic mitral annular velocity (E/e') ≥15 left atrial volume index (LAVI) >34 mL/m2 septal early diastolic mitral annular velocity (e') <7 cm/second or tricuspid regurgitation (TR) maximum velocity >2.8 m/second in the absence of pulmonary hypertension (HTN) and the presence of measurable early to late diastolic trans mitral flow velocity (E/A) ratio (E/A >2 = grade 3 E/A 0.8-2 = grade 2)'. LVDD will be classified as "of indeterminate grade" when only 2 of the 4 criteria are met. The supporting criteria for diagnosis of LVDD are changes in cardiac chamber sizes electrophysiological abnormalities increased biomarkers like N terminal pro-brain natriuretic peptide (NT-Pro BNP) and troponin I.
- Being tested
- Empagliflozin + Carvedilol, Carvedilol
- Keywords
- Empagliflozin in cirrhosis, Carvedilol in Cirrhosis, SGLT-2 inhibitor, Ascites, Diastolic heart failure, heart failure with preserved ejection fraction
- Medical subject headings
- Fibrosis, Ascites, Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin + CarvedilolDrug
Patient Recruitment:
The study participants are all cirrhosis patients receiving treatment at PGIMER Chandigarh. Eligible participants meeting LVDD criteria per the CCM Consortium 2020 consensus.
Carvedilol Dosing protocol in this study Patients will be given carvedilol in a starting dose of 3.125 mg twice daily. The dose will be titrated weekly to achieve a target heart rate of 50-60/ min taking care that side effects such as hypotension bronchospasm excessive bradycardia are not seen. The maximum dosage allowed as per prior trial data is 25 mg per day.
Empagliflozin Dosing protocol in this Study:
- All patients will receive a standard dose of Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes.
CarvedilolDrug
- Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate 10 mg placebo pill
- Standard Medical Therapy
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Empagliflozin + Carvedilol-arm | Active comparator | Experimental: Empagliflozin + Carvedilol-arm
* Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes for 1 year from randomization
* Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate
* Standard Medical Therapy for liver disease as per clinician decision Receives: Drug: Empagliflozin + Carvedilol |
| 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 10 mg placebo administered once daily.
* Standard Medical Therapy prescribed as per clinician decision Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite end point of decompensation event and/or death
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 LVDD
Measured: From enrolment through study completion, an average of 1 year
Secondary outcomes (17)
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging
Septal E/e' ratio
Measured: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging Septal e' velocity
Measured: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging
Left atrial volume index
Measured: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Improvement in CCM parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging
Tricuspid regurgitant Velocity
Measured: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Improvement in Cardiac systolic function (Cardiac Index) in either arm based on Echocardiography and Cardiac Imaging
Measured: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Improvement in Cardiac systolic function (Ejection Fraction) in either arm based on Echocardiography and Cardiac Imaging
Measured: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Improvement in Cardiac systolic function (Global Longitudinal Strain) in either arm based on Echocardiography and Cardiac Imaging
Measured: From enrolment through study completion, an average of 1 year
Hospitalization events
- Episodes warranting hospitalization
Measured: From enrolment through study completion, an average of 1 year
• Serum level of NT-proBNP
Cardiac biomarkers
Measured: At enrolment
• Serum level of NT-proBNP
Cardiac biomarkers
Measured: At 6 months from enrolment
• Serum level of NT-proBNP
Cardiac biomarkers
Measured: At 12 months from enrolment
• Serum level of Galectin-3
Cardiac biomarkers
Measured: At enrolment
• Serum level of Galectin 3
Cardiac biomarkers
Measured: At 6 months from enrolment
• Serum level of Galectin 3
Cardiac biomarkers
Measured: At 12 months from enrolment
• Serum level of Aldosterone
Cardiac biomarkers
Measured: At enrolment
• Serum level of Aldosterone
Cardiac biomarkers- Renin angiotensin aldosterone system
Measured: At 6 months from enrolment
• Serum level of Aldosterone
Cardiac biomarkers- Renin angiotensin aldosterone system
Measured: At 12 months from enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2026
- Study start1 Apr 2026
- Primary completion30 Jan 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cirrhotic CardiomyopathyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double Blind Placebo controlled Randomized Controlled Trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07322237
- Sponsor's protocol ID
- PGI/IEC/2025/SPL-865
- Acronym
- DICE
- Status last verified
- May 2026
- First submitted
- 30 Nov 2025
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This database has identifier information
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empagliflozin + Carvedilol vs. Carvedilol Alone for Patients With Cirrhosis and Left Ventricular Diastolic Dysfunction and Impact on Hepatic Decompensation and Survival: A Double-Blind Placebo-Controlled Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07322237
- Acronym / sponsor ID
- DICE / PGI/IEC/2025/SPL-865
- Keywords
- Empagliflozin in cirrhosis, Carvedilol in Cirrhosis, SGLT-2 inhibitor, Ascites, Diastolic heart failure, heart failure with preserved ejection fraction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- 30 Jan 2029 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 7 Jan 2026 (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.
- This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. The drug has been found to be useful in large trials on heart failure with preserved ejection fraction in the general population with improvement in MASLD progression, with improvement in body weight and hepatic steatosis but no change in liver fibrosis.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the development and progression of heart failure in patients with type 2 diabetes and in those with heart failure and a reduced and preserved ejection fraction. In patients with cirrhosis safety of empagliflozin in a dose of 10 mg has been demonstrated.
- Prevention of decompensation related events in cirrhosis is the key endpoint of any liver-directed therapy as the median survival in the compensated state exceeds 10 years but median survival in the decompensated state approximates 1.5 years. Previous data has demonstrated the risk of hepatic decompensation acute kidney injury and poor survival in patients with cirrhosis and heart failure with preserved ejection fraction (HFpEF) i.e. LVDD a large subset of whom meet criteria for CCM.
Detailed description
New diagnostic criteria for cirrhotic cardiomyopathy For the diagnosis of cirrhotic cardiomyopathy (CCM) we will use criteria proposed by the CCM consortium in 2020 with modification to take septal e' and E/e' readings. In accordance with the recent CCM criteria 'systolic dysfunction is defined as an ejection fraction (EF) of 50% or less or an absolute value of GLS <18%. LVDD grade will be determined if 3 of the following 4 criteria are met: early diastolic trans mitral flow to early diastolic mitral annular velocity (E/e') ≥15 left atrial volume index (LAVI) >34 mL/m2 septal early diastolic mitral annular velocity (e') <7 cm/second or tricuspid regurgitation (TR) maximum velocity >2.8 m/second in the absence of pulmonary hypertension (HTN) and the presence of measurable early to late diastolic trans mitral flow velocity (E/A) ratio (E/A >2 = grade 3 E/A 0.8-2 = grade 2)'. LVDD will be classified as "of indeterminate grade" when only 2 of the 4 criteria are met. The supporting criteria for diagnosis of LVDD are changes in cardiac chamber sizes electrophysiological abnormalities increased biomarkers like N terminal pro-brain natriuretic peptide (NT-Pro BNP) and troponin I.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double Blind Placebo controlled Randomized Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| Experimental: Empagliflozin + Carvedilol-arm | Active comparator | Drug: Empagliflozin + CarvedilolExperimental: Empagliflozin + Carvedilol-arm * Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes for 1 year from randomization * Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate * Standard Medical Therapy for liver disease as per clinician decision |
| Active Comparator: Carvedilol arm | Active comparator | Drug: Carvedilol* Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate 10 mg placebo administered once daily. * Standard Medical Therapy prescribed as per clinician decision |
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
- Cirrhosis as diagnosed by histology or clinical laboratory and USG findings
- LVDD (with EF>50%) on 2D echocardiography with TDI
- Written informed consent.
Key exclusion criteria (15 listed)
- Age >65 years
- Serum Creatinine>2 mg/dl
- History of urinary tract /genital infections in last 3 months
- Patient on treatment with statin (one month before the study)
- Advanced Cirrhosis (MELD>20)
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 |
|---|---|---|
| Empagliflozin + CarvedilolPatient Recruitment: The study participants are all cirrhosis patients receiving treatment at PGIMER Chandigarh. Eligible participants meeting LVDD criteria per the CCM Consortium 2020 consensus. Carvedilol Dosing protocol in this study Patients will be given carvedilol in a starting dose of 3.125 mg twice daily. The dose will be titrated weekly to achieve a target heart rate of 50-60/ min taking care that side effects such as hypotension bronchospasm excessive bradycardia are not seen. The maximum dosage allowed as per prior trial data is 25 mg per day. Empagliflozin Dosing protocol in this Study: • All patients will receive a standard dose of Empagliflozin fixed dose of 10 mg per day in patients with or without diabetes. | Drug | Experimental: Empagliflozin + Carvedilol-arm |
| Carvedilol* Carvedilol: Starting dose of 3.125 mg twice daily targeted upwards q 7 days to achieve target heart rate 10 mg placebo pill * Standard Medical Therapy | Drug | Active Comparator: Carvedilol arm |
Primary outcome
Composite end point of decompensation event and/or death
Time frame: From enrolment through study completion, an average of 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 LVDD
17 secondary outcomes
Improvement in Cardiac Diastolic Function
Time frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Time frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Time frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Diastolic Function
Time frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Time frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Time frame: From enrolment through study completion, an average of 1 year
Improvement in Cardiac Systolic Function
Time frame: From enrolment through study completion, an average of 1 year
Hospitalization events
Time frame: From enrolment through study completion, an average of 1 year
• Serum level of NT-proBNP
Time frame: At enrolment
• Serum level of NT-proBNP
Time frame: At 6 months from enrolment
• Serum level of NT-proBNP
Time frame: At 12 months from enrolment
• Serum level of Galectin-3
Time frame: At enrolment
• Serum level of Galectin 3
Time frame: At 6 months from enrolment
• Serum level of Galectin 3
Time frame: At 12 months from enrolment
• Serum level of Aldosterone
Time frame: At enrolment
• Serum level of Aldosterone
Time frame: At 6 months from enrolment
• Serum level of Aldosterone
Time frame: At 12 months from enrolment
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 14 May 2026.
- Individual participant dataSharing planned: No. This database has identifier information
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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.
Madumita Premkumar contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin + Carvedilol and Carvedilol in people with Cirrhotic Cardiomyopathy and Empagliflozin, 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 15 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 14 May 2026. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Madhumita Premkumar, MD DM (01722754777, drmadhumitap@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite end point of decompensation event and/or death (time frame: From enrolment through study completion, an average of 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 14 May 2026.