Clinical trial NCT01676285: Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis
Official title: Effect of Metoprolol Succinate in Cardiac Remodeling Related to Nonalcoholic Cirrhosis. Randomized Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cirrhosis
Cirrhotic Cardiomyopathy
Cardiac Remodeling
Keywords: Cirrhosis
cirrhotic cardiomyopathy
cardiac remodeling
cardiomyopathy
metoprolol succinate
betablockers
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2012-08-30
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Improvement of systolic function
timeFrame: six months
Secondary outcomes:
measure: Improvement in left ventricular diastolic function
timeFrame: six months
measure: Renal function
timeFrame: From randomization until six months
measure: Serum level of BNP, catecholamines, plasmatic renin activity
timeFrame: Six months
measure: Mortality
timeFrame: From randomization until six months of follow up
measure: Quality of life
timeFrame: Six months
measure: Electrophysiologic modifications
timeFrame: Six months
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: University of Sao Paulo School of Medicine
Study officials:
affiliation: University of Sao Paulo School of Medicine
name: Fernando Bacal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: