Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis

NCT ID: NCT01676285

Last Updated: 2014-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2014-03-31

Brief 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. 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.

Conditions

Cirrhosis; Cirrhotic Cardiomyopathy; Cardiac Remodeling

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metoprolol succinate

Metoprolol succinate

Group Type: ACTIVE_COMPARATOR

Metoprolol succinate

Intervention Type: DRUG

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Follow up

Group without cirrhotic cardiomyopathy, only follow up without randomization.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metoprolol succinate

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Selozok

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Fernando Bacal

MD; PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fernando Bacal, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo School of Medicine

Locations

University of Sao Paulo School of Medicine

São Paulo, São Paulo, Brazil

Countries

Brazil

Other Identifiers

0010/11

Identifier Type: -

Identifier Source: org_study_id