Efficacy of Carvedilol + Ivabradine vs Carvedilol Alone for Left Ventricular Diastolic Dysfunction in Chronic Liver Disease Patients and Its' Impact on Morbidity and Mortality; a Prospective Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Survival
研究概览
简要总结
A total of 130 patients with liver cirrhosis who fulfill the criteria of the study, and who have been found to have left ventricular diastolic dysfunction on a screening 2D echocardiography, will then be randomized by Block randomization technique, to two arms in a ratio 1:1(Group A) will receive carvedilol+ Ivabradine targeted therapy for heart rate reduction while Group B will receive Carvedilol alone; and the dosage of drug in the treatment arm will be titrated every week to achieve target heart rate of 50-60/ minute. Patients in the treatment arms, who are unable to tolerate carvedilol due to hypotension episodes, will be offered ivabradine alone to allow achievement of targeted heart rate reduction. All patients will be evaluated at 0,6, and 12 months. The end points will be clinical events, cardiac function improvement, renal function, and mortality.
详细描述
The investigators have already demonstrated the role of targeted heart rate reduction in the management of LVDD in cirrhosis, but the previous study could not demonstrate the role of ivabradine alone in absence of betablocker therapy. This trial will be a validation cohort for the initial data obtained on this novel drug. The use of ivabradine can treat patients who do not tolerate betablocker therapy due to contraindications or adverse effects especially hypotension.
Diagnosis of CCM will be as per 2020 CCMC criteria. CCM is defined as systolic or diastolic dysfunction in the absence of alternative cardiac pathology in concordance with the Cirrhotic Cardiomyopathy Consortium (CCMC) criteria. 9 Systolic dysfunction was defined as an ejection fraction (EF) ≤50% or an absolute value of GLS <18%. CCM will defined as presence of 3 of the following 4 criteria: septal early diastolic mitral annular flow velocity (e') <7 cm/s, early diastolic transmitral flow to early diastolic mitral annular velocity (E/e') ≥15, left atrial volume index (LAVI) >34 mL/m2, tricuspid jet maximum velocity >2.8 m/s, in the absence of pulmonary hypertension and the presence of measurable early to late diastolic transmitral flow velocity (E/A) ratio (E/A >2 = grade 3 & E/A 0.8-2 = grade 2 LVDD). Persons meeting only 2 criteria will be termed as indeterminate for LVDD grade.
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
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age range of 18-65 years
- •Cirrhosis, as diagnosed by histology or clinical, laboratory and USG findings,
- •LV diastolic dysfunction on 2D echocardiography
排除标准
- •Chronic renal disease
- •Patient already on beta blocker
- •Pregnancy and peripartum cardiomyopathy
- •Hypertension
- •Coronary artery disease
- •Valvular heart disease
- •Sick sinus syndrome/ Pacemaker
- •Cardiac rhythm disorder
- •Hypothyroidism
- •Hyperthyroidism
- •Portal vein thrombosis
- •Transjugular intrahepatic porto systemic shunt (TIPS) insertion
- •Hepatocellular carcinoma
- •Anemia Hb < 8gm/dl in females, and < 9 gm/dl in males
研究组 & 干预措施
Carvedilol + Ivabradine
干预措施: Betablocker + ivabradine (Drug)
Carvedilol
干预措施: Betablocker (Drug)
结局指标
主要结局
Survival
时间窗: 12 months
All cause mortality to be assessed
次要结局
- Change in E/e' Ratio(12 months)
- Change in renal function(12 months)
- Change in HRQoL(12 months)
- Change in neurohormonal markers- Brain natriuretic peptide, aldosterone, plasma renin activity(12 months)
- Number of Episodes of Cirrhosis related events(12 months)
研究者
Madhumita Premkumar
Assistant Professor and Principal Investigator, Department of Hepatology
Post Graduate Institute of Medical Education and Research, Chandigarh