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临床试验/NCT01676285
NCT01676285已完成3 期

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

University of Sao Paulo1 个研究点 分布在 1 个国家目标入组 125 人开始时间: 2012年1月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
入组人数
125
试验地点
1
主要终点
Improvement of systolic function

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 60 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • more than 18 years old.
  • must have signed the written informed consent.
  • nonalcoholic cirrhosis.

排除标准

  • 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)

研究组 & 干预措施

Metoprolol succinate

Active Comparator

Metoprolol succinate

干预措施: Metoprolol succinate (Drug)

Placebo

Placebo Comparator

Placebo

干预措施: placebo (Drug)

结局指标

主要结局

Improvement of systolic function

时间窗: six months

Systolic functional reserve is measured by aortic velocity time integral in echocardiographic at rest and stress with dobutamine.

次要结局

  • Improvement in left ventricular diastolic function(six months)
  • Renal function(From randomization until six months)
  • Serum level of BNP, catecholamines, plasmatic renin activity(Six months)
  • Mortality(From randomization until six months of follow up)
  • Quality of life(Six months)
  • Electrophysiologic modifications(Six months)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Fernando Bacal

MD; PhD

University of Sao Paulo

研究点 (1)

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