CirrhosisPhase 3CARE CirrhosisNCT01676285
Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis
A Phase 3 study testing Metoprolol succinate in people with Cirrhosis and Cirrhotic Cardiomyopathy, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
Cirrhotic cardiomyopathy is defined as a chronic cardiac dysfunction in patients with cirrhosis. It is suspected that this specific cardiac dysfunction contributes to the onset of complications in liver disease. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Cirrhosis, Cirrhotic Cardiomyopathy, Cardiac Remodeling
- What is being tested?
- Metoprolol succinate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2012to Mar 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- more than 18 years old.
- must have signed the written informed consent.
- nonalcoholic cirrhosis.
Who cannot join
- Betablockers intolerance;
- Diagnosis of other cardiomyopathy
- Chronicle renal disease (Creatinine > 2.5)
- Heavy alcohol intake history
- Presence of other disease with possible cardiac implication (infiltrative or storage disease)
Trial locations and contacts
1 site in 1 country.
Brazil1 site
University of Sao Paulo School of Medicine
São Paulo, São Paulo, 05403000
About this study
Official title: Effect of Metoprolol Succinate in Cardiac Remodeling Related to Nonalcoholic Cirrhosis. Randomized Study.
Cirrhotic cardiomyopathy is defined as a chronic cardiac dysfunction in patients with cirrhosis. It is suspected that this specific cardiac dysfunction contributes to the onset of complications in liver disease. The purpose of this prospective, randomized trial is to determine whether metoprolol succinate can revert cardiac dysfunction secondary to cirrhosis (cirrhotic cardiomyopathy), and prevent complications (renal dysfunction, mortality). A total of 100 patients with cirrhotic cardiomyopathy will be randomized (Group R) to receive metoprolol succinate or placebo; other 25 patients without cirrhotic cardiomyopathy (Group F) will only be followed up without medication. All patients will be evaluated in the beginning and again after six months. The assessment protocol includes clinical evaluation, electrocardiogram, echocardiogram, laboratory analysis and life quality questionaire. The end points will be cardiac remodeling, electrophysiologic changes, sympathetic activity, laboratory issue changes, renal function, quality of life, and mortality.
Read the detailed description
Cirrhotic cardiomyopathy (CMC) is defined as a chronic cardiac dysfunction in patients with cirrhosis. Moreover, it is characterized by an abnormal and blunted response to pathological or pharmacological stress in the absence of any other associated cardiac disease. The diagnostic criteria are: baseline increased cardiac output, attenuated myocardial contractile response to stress, diastolic dysfunction, and electrophysiological repolarization abnormalities. It is suspected that cardiac dysfunction in cirrhosis contribute to the onset of complications in liver disease. We will investigate the effect of metoprolol succinate in the reversal of cardiac dysfunction and prevention of complications of cirrhosis in patients with cirrhotic cardiomyopathy. Furthermore, we want to study the influence of presence of CMC in the evolution of cirrhotic patients. The study will be prospective, randomized, double-blind, and placebo-controlled. The sample consists of 125 patients aged between 18 and 60 years old diagnosed with severe liver cirrhosis (Child B or C or MELD score above 10) with cirrhotic cardiomyopathy or not. Of these, 100 patients with cirrhotic cardiomyopathy will be randomized into two groups: group R1 (metoprolol succinate) and group R2 (placebo). Group F will consist of cirrhotic patients without cardiomyopathy and will not receive medication. Patients will be evaluated by clinical examination, resting electrocardiogram, 24-hour Holter, stress echocardiography and laboratory (brain natriuretic peptide (BNP), catecholamines, plasma renin activity, and troponin) at inclusion and after six months. The end points are: 1) Reversal of cardiac dysfunction in patients with cirrhotic cardiomyopathy, 2) Development of hepatorenal syndrome, 3) Reversal of the electrophysiologic abnormalities, 4)Changes in laboratory tests, and 5) Mortality.
- Conditions
- Cirrhosis, Cirrhotic Cardiomyopathy, Cardiac Remodeling
- Being tested
- Metoprolol succinate, placebo
- Keywords
- Cirrhosis, cirrhotic cardiomyopathy, cardiac remodeling, cardiomyopathy, metoprolol succinate, betablockers
- Medical subject headings
- Fibrosis, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol succinateDrug
Also called Selozok
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol succinate | Active comparator | Metoprolol succinate Receives: Drug: Metoprolol succinate |
| Placebo | Placebo comparator | Placebo Receives: Drug: placebo |
| Follow up | No intervention | Group without cirrhotic cardiomyopathy, only follow up without randomization. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of systolic function
Systolic functional reserve is measured by aortic velocity time integral in echocardiographic at rest and stress with dobutamine.
Measured: six months
Secondary outcomes (6)
Improvement in left ventricular diastolic function
Measured: six months
Renal function
Measured: From randomization until six months
Serum level of BNP, catecholamines, plasmatic renin activity
Measured: Six months
Mortality
Measured: From randomization until six months of follow up
Quality of life
Measured: Six months
Electrophysiologic modifications
QT prolongation R-R variability
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2012 (estimated)
- Study startJan 2012
- Primary completionSep 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Principal investigator, Fernando Bacal, University of Sao Paulo
- Investigators
- Fernando Bacal, MD, PhD, Principal investigator, University of Sao Paulo School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01676285
- Sponsor's protocol ID
- 0010/11
- Acronym
- CARE Cirrhosis
- Status last verified
- Sep 2014
- First submitted
- 28 Aug 2012
- Last updated
- 11 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metoprolol Succinate in Cardiac Remodeling Related to Nonalcoholic Cirrhosis. Randomized Study.
- ClinicalTrials.gov ID
- NCT01676285
- Acronym / sponsor ID
- CARE Cirrhosis / 0010/11
- Conditions
- Cirrhosis, Cirrhotic Cardiomyopathy, Cardiac Remodeling
- Keywords
- Cirrhosis, cirrhotic cardiomyopathy, cardiac remodeling, cardiomyopathy, metoprolol succinate, betablockers
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Jan 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 30 Aug 2012 (estimated)
- 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.
Cirrhotic cardiomyopathy is defined as a chronic cardiac dysfunction in patients with cirrhosis. It is suspected that this specific cardiac dysfunction contributes to the onset of complications in liver disease. The purpose of this prospective, randomized trial is to determine whether metoprolol succinate can revert cardiac dysfunction secondary to cirrhosis (cirrhotic cardiomyopathy), and prevent complications (renal dysfunction, mortality). A total of 100 patients with cirrhotic cardiomyopathy will be randomized (Group R) to receive metoprolol succinate or placebo; other 25 patients without cirrhotic cardiomyopathy (Group F) will only be followed up without medication. All patients will be evaluated in the beginning and again after six months. The assessment protocol includes clinical evaluation, electrocardiogram, echocardiogram, laboratory analysis and life quality questionaire. The end points will be cardiac remodeling, electrophysiologic changes, sympathetic activity, laboratory issue changes, renal function, quality of life, and mortality.
Detailed description
Cirrhotic cardiomyopathy (CMC) is defined as a chronic cardiac dysfunction in patients with cirrhosis. Moreover, it is characterized by an abnormal and blunted response to pathological or pharmacological stress in the absence of any other associated cardiac disease. The diagnostic criteria are: baseline increased cardiac output, attenuated myocardial contractile response to stress, diastolic dysfunction, and electrophysiological repolarization abnormalities. It is suspected that cardiac dysfunction in cirrhosis contribute to the onset of complications in liver disease. We will investigate the effect of metoprolol succinate in the reversal of cardiac dysfunction and prevention of complications of cirrhosis in patients with cirrhotic cardiomyopathy. Furthermore, we want to study the influence of presence of CMC in the evolution of cirrhotic patients. The study will be prospective, randomized, double-blind, and placebo-controlled. The sample consists of 125 patients aged between 18 and 60 years old diagnosed with severe liver cirrhosis (Child B or C or MELD score above 10) with cirrhotic cardiomyopathy or not. Of these, 100 patients with cirrhotic cardiomyopathy will be randomized into two groups: group R1 (metoprolol succinate) and group R2 (placebo). Group F will consist of cirrhotic patients without cardiomyopathy and will not receive medication. Patients will be evaluated by clinical examination, resting electrocardiogram, 24-hour Holter, stress echocardiography and laboratory (brain natriuretic peptide (BNP), catecholamines, plasma renin activity, and troponin) at inclusion and after six months. The end points are: 1) Reversal of cardiac dysfunction in patients with cirrhotic cardiomyopathy, 2) Development of hepatorenal syndrome, 3) Reversal of the electrophysiologic abnormalities, 4)Changes in laboratory tests, and 5) Mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Metoprolol succinate | Active comparator | Drug: Metoprolol succinateMetoprolol succinate |
| Placebo | Placebo comparator | Drug: placeboPlacebo |
| Follow up | No intervention | –Group without cirrhotic cardiomyopathy, only follow up without randomization. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- more than 18 years old.
- must have signed the written informed consent.
- nonalcoholic cirrhosis.
Key exclusion criteria (5 listed)
- Betablockers intolerance;
- Diagnosis of other cardiomyopathy
- Chronicle renal disease (Creatinine > 2.5)
- Heavy alcohol intake history
- Presence of other disease with possible cardiac implication (infiltrative or storage disease)
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 |
|---|---|---|
| Metoprolol succinateAlso: Selozok | Drug | Metoprolol succinate |
| placebo | Drug | Placebo |
Primary outcome
Improvement of systolic function
Time frame: six months
Systolic functional reserve is measured by aortic velocity time integral in echocardiographic at rest and stress with dobutamine.
6 secondary outcomes
Improvement in left ventricular diastolic function
Time frame: six months
Renal function
Time frame: From randomization until six months
Serum level of BNP, catecholamines, plasmatic renin activity
Time frame: Six months
Mortality
Time frame: From randomization until six months of follow up
Quality of life
Time frame: Six months
Electrophysiologic modifications
Time frame: Six months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2014.
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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. This study is not recruiting at the moment.
Fernando Bacal, MD, PhD principal investigator
University of Sao Paulo School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metoprolol succinate in people with Cirrhosis and Cirrhotic Cardiomyopathy, run by University of Sao Paulo at 1 site in Brazil.
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 3 inclusion and 5 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: finished, as of the sponsor's last update on 11 Sep 2014. 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 Brazil. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of systolic function (time frame: six months). 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 11 Sep 2014; AzTrials last refreshed its copy on 8 Nov 2026.