Carvedilol + Simvastatin vs. Carvedilol alone for Chronic Liver Disease and Cirrhotic cardiomyopathy and its impact on hepatic decompensation and survival; a double-blind randomized controlled trial.
试验速览
- 阶段
- Phase 3 4
- 状态
- 招募中
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- The primary outcome measure is defined as a composite end point of acute decompensation event (acute variceal bleeding, new ascites or recurrence of previously controlled ascites, episode of hepatic encephalopathy or acute kidney injury), death in the participants.
研究概览
简要总结
Cirrhosis and portal hypertension are associated with hyperdynamic circulation and decompensation events, including development of ascites, variceal bleeding, acute kidney injury, and susceptibility to infections.
Rationale:
Cirrhosis and portal hypertension are associated with hyperdynamic circulation and decompensation events, including ascites, variceal bleeding, acute kidney injury, and susceptibility to infections. CCM, present in 25-30 % of patients, is characterized by structural and functional abnormalities in the heart, and is associated with progression of cirrhosis, impaired quality of life and poor survival. Statins play a crucial role in reducing proatherogenic LDL cholesterol levels, making them a cornerstone in managing diabetes and cardiovascular diseases (CVDs) with the aim of decreasing or reversing atherosclerosis. This trial aims to evaluate the impact and safety of simvastatin in cirrhotic cardiomyopathy.
Novelty: Simvastatin might be of special value in diastolic dysfunction through its hemodynamic and functional effects on LV remodeling and improve portal hemodynamics through the pleotropic effects of lipophilic statins.
Objectives:
The primary objective is to assess the combined effects of carvedilol and simvastatin in managing CCM vs carvedilol alone for a composite outcome to prevent decompensation and reduce all-cause mortality. We will comprehensively evaluate cardiac function, decompensation events and survival based on impact of simvastatin over the standard betablocker carvedilol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Age range of 18 to 65 years Compensated cirrhosis as diagnosed by histology or clinical laboratory and USG findings CCM with EF less than 50 percent on 2D echocardiography with TDI Written informed consent.
排除标准
- •Age more than 65 years Serum Creatinine more than 2 mg per dl Patient previously treated with statin one month before the study Contraindications to statins Advanced Cirrhosis CTP score more than 9 or Child C will be excluded Coronary artery disease Sick sinus syndrome Pacemaker valvular heart disease Cardiac rhythm disorder Peripartum cardiomyopathy Portopulmonary hypertension hepatopulmonary syndrome Transjugular intrahepatic porto systemic shunt TIPS insertion Hepatocellular carcinoma Pregnancy or lactation Patients with HIV or retroviral therapy Anemia Hb less than 8gm per dl in females and less than 9 gm per dl in males Acute variceal bleeding in last 6 months Need for medications metabolized by CYP3A4 such as amlodipine verapamil fenofibrate azole antibiotics protease inhibitors etc.
结局指标
主要结局
The primary outcome measure is defined as a composite end point of acute decompensation event (acute variceal bleeding, new ascites or recurrence of previously controlled ascites, episode of hepatic encephalopathy or acute kidney injury), death in the participants.
时间窗: At 1 year from enrolment
次要结局
- Improvement in cirrhotic cardiomyopathy parameters (left ventricular diastolic function) in either arm based on Echocardiography and Cardiac Imaging.(1 YEAR)
- Any episodes which warranted hospitalization of the participants.(1 YEAR)
- Serum level of BNP and other cardiac and inflammatory biomarkers will be assessed and correlated clinically.(1 YEAR)
研究者
Dr Madhumita Premkumar
Post Graduate Institute of Medical Education & Research, Chandigarh