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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by University of Sao Paulo
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Fernando Bacal, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT01676285
First received: August 28, 2012
Last updated: August 29, 2012
Last verified: August 2012
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 University of Sao Paulo:

Primary Outcome Measures:
  • Improvement of systolic function [ Time Frame: six months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Renal function [ Time Frame: From randomization until six months ] [ Designated as safety issue: Yes ]
  • Serum level of BNP, catecholamines, plasmatic renin activity [ Time Frame: Six months ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: From randomization until six months of follow up ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Six months ] [ Designated as safety issue: No ]
  • Electrophysiologic modifications [ Time Frame: Six months ] [ Designated as safety issue: No ]
    QT prolongation R-R variability


Estimated Enrollment: 125
Study Start Date: January 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01676285

Contacts
Contact: Fernando Bacal, MD, PhD +551126613338 fbacal@uol.com.br
Contact: Odilson M Silvestre, MD +551126613338 odilsonsilvestre@yahoo.com.br

Locations
Brazil
University of Sao Paulo School of Medicine Recruiting
Sao Paulo, Brazil, 05403000
Contact: Fernando Bacal, MD, PhD    +551126613338    fbacal@uol.com.br   
Contact: Odilson M Silvestre, MD    +551126617830    odilsonsilvestre@yahoo.com.br   
Principal Investigator: Fernando Bacal, MD, PhD         
Sub-Investigator: Odilson M Silvestre, MD         
Sub-Investigator: Alberto Q Farias, MD, PhD         
Sub-Investigator: Flair J Carrilho, DM, PhD         
Sub-Investigator: Luiz AC D'Albuquerque, MD, PhD         
Sub-Investigator: José L Andrade         
Sub-Investigator: Meive Furtado, MD         
Sub-Investigator: Daniel F Mazo, MD         
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

No publications provided

Responsible Party: Fernando Bacal, MD; PhD, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT01676285     History of Changes
Other Study ID Numbers: 0010/11
Study First Received: August 28, 2012
Last Updated: August 29, 2012
Health Authority: Brazil: National Commission of Ethic in Researches - CONEP

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

Additional relevant MeSH terms:
Liver Cirrhosis
Fibrosis
Cardiomyopathies
Liver Diseases
Digestive System Diseases
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Metoprolol
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on July 31, 2014