Metoprolol Succinate in Cardiac Remodeling Related to Cirrhosis (CARE Cirrhosis)
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.
Drug: Metoprolol succinate
|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.|
- 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.
- 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
|Study Start Date:||January 2012|
|Study Completion Date:||March 2014|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Metoprolol succinate
Drug: Metoprolol succinate
Other Name: Selozok
Placebo Comparator: Placebo
No Intervention: Follow up
Group without cirrhotic cardiomyopathy, only follow up without randomization.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01676285
|University of Sao Paulo School of Medicine|
|Sao Paulo, Brazil, 05403000|
|Principal Investigator:||Fernando Bacal, MD, PhD||University of Sao Paulo School of Medicine|