Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis
Condition: Cirrhosis; Cirrhotic Cardiomyopathy; Cardiac Remodeling
MeSH terms: Liver Cirrhosis; Cardiomyopathies; Fibrosis
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Metoprolol succinate; placebo
Intervention type(s): Drug; Drug
Other intervention name(s): Selozok
Intervention MeSH terms: Metoprolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cirrhosis; cirrhotic cardiomyopathy; cardiac remodeling; cardiomyopathy; metoprolol succinate; betablockers