Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis

Cirrhosis Clinical Trial

— CARE Cirrhosis  

Official title:

Effect of Metoprolol Succinate in Cardiac Remodeling Related to Nonalcoholic Cirrhosis. Randomized Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01676285
• Other study ID #: 0010/11
• Status: Completed
• Phase: Phase 3
• First received: August 28, 2012
• Last updated: September 9, 2014
• Start date: January 2012
• Est. completion date: March 2014

Study information

• Verified date: September 2014
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Commission of Ethic in Researches - CONEP
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: March 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Remodeling
• Cardiomyopathies
• Cirrhosis
• Cirrhotic Cardiomyopathy
• Liver Cirrhosis

Intervention

Drug:
• Metoprolol succinate

• placebo

Locations

Country	Name	City	State
Brazil	University of Sao Paulo School of Medicine	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of systolic function	Systolic functional reserve is measured by aortic velocity time integral in echocardiographic at rest and stress with dobutamine.	six months	Yes
Secondary	Improvement in left ventricular diastolic function		six months	No
Secondary	Renal function		From randomization until six months	Yes
Secondary	Serum level of BNP, catecholamines, plasmatic renin activity		Six months	No
Secondary	Mortality		From randomization until six months of follow up	Yes
Secondary	Quality of life		Six months	No
Secondary	Electrophysiologic modifications	QT prolongation R-R variability	Six months	No