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Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis (CARE Cirrhosis)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01676285
First Posted: August 30, 2012
Last Update Posted: September 11, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Fernando Bacal, University of Sao Paulo
  Purpose
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.

Condition Intervention Phase
Cirrhosis Cirrhotic Cardiomyopathy Cardiac Remodeling Drug: Metoprolol succinate Drug: placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Metoprolol Succinate in Cardiac Remodeling Related to Nonalcoholic Cirrhosis. Randomized Study.

Resource links provided by NLM:


Further study details as provided by Fernando Bacal, University of Sao Paulo:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]
    QT prolongation R-R variability


Enrollment: 125
Study Start Date: January 2012
Study Completion Date: March 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metoprolol succinate
Metoprolol succinate
Drug: Metoprolol succinate
Other Name: Selozok
Placebo Comparator: Placebo
Placebo
Drug: placebo
No Intervention: Follow up
Group without cirrhotic cardiomyopathy, only follow up without randomization.

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.
  Eligibility

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • more than 18 years old.
  • must have signed the written informed consent.
  • nonalcoholic cirrhosis.

Exclusion Criteria:

  • 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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01676285


Locations
Brazil
University of Sao Paulo School of Medicine
Sao Paulo, Brazil, 05403000
Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Fernando Bacal, MD, PhD University of Sao Paulo School of Medicine
  More Information

Responsible Party: Fernando Bacal, MD; PhD, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT01676285     History of Changes
Other Study ID Numbers: 0010/11
First Submitted: August 28, 2012
First Posted: August 30, 2012
Last Update Posted: September 11, 2014
Last Verified: September 2014

Keywords provided by Fernando Bacal, University of Sao Paulo:
Cirrhosis
cirrhotic cardiomyopathy
cardiac remodeling
cardiomyopathy
metoprolol succinate
betablockers

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Cardiomyopathies
Pathologic Processes
Liver Diseases
Digestive System Diseases
Heart Diseases
Cardiovascular Diseases
Metoprolol
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action