A Multi-center, Randomized, Open-label, Active-controlled, 12-week Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure
试验速览
- 阶段
- 不适用
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- Left ventricular ejection fraction (LVEF)
研究概览
简要总结
Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, and has been recently indicated as a new treatment option with a strong level of recommendation (class I, level of evidence B) in the main international guidelines. Cardiovascular disease (CVD) is the most common cause of death in end stage renal disease (ESRD) patients undergoing hemodialysis (HD). Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. So far, no data available about the efficacy and safety of sacubitril/valsartan in ESRD patients undergoing hemodialysis, although this medication was noted to be effective and comparably well tolerable in those with estimated glomerular filtration rate(eGFR) 20 to 60 mL/min/1.73 m2 in the United Kingdom Heart and Renal Protection-III trial.
The purpose of this open label, randomized controlled study with prospective data collection is to assess the efficacy and safety of sacubitril/valsartan in maintenance hemodialysis patients with heart failure.
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
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained before any study assessment is performed.
- •End stage renal disease (ESRD) patients (eGFR<15ml/min/1.73m² as measured by the Chronic Kidney Disease Epidemiology Collaboration formula at screening) who have been receiving hemodialysis 3 times a week for at least 12 weeks before registration.
- •Chronic heart failure (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 50%.
- •Mean sitting systolic blood pressure(msSBP)≥110 mmHg.
- •Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker for at least 2 weeks.
- •Good compliance.
排除标准
- •Acute renal failure with hemodialysis.
- •Isolated right heart failure owing to pulmonary disease, primary cause of dyspnea due to noncardiac, non-HF causes such as acute or chronic respiratory disorders.
- •Systolic blood pressure lower than 100 mmHg at screening (<95 mmHg at the randomization visit).
- •Previous history of intolerance to recommended target doses of angiotensin receptor blockers.
- •Significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy (such as serum potassium>5.5 or <3.5mmol/L, serum sodium<130mmol/L or alanine aminotransferase or aspartate aminotransferase>2 times the upper limit of the normal range)
- •History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes.
- •History of angioedema.
- •Any medications that have potential for drug-drug interaction with LCZ696 will not be allowed during the study.
- •Pregnant female.
- •Use of sacubitril/valsartan prior to week-2.
研究组 & 干预措施
Sacubitril/valsartan
Patients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous angiotensin converting enzyme inhibitor(ACEI), ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks.
干预措施: Sacubitril / Valsartan Oral Tablet [Entresto] (Drug)
Valsartan
Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.
干预措施: Valsartan 80mg Tablet (Drug)
结局指标
主要结局
Left ventricular ejection fraction (LVEF)
时间窗: 12 weeks
Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study
次要结局
- Concentration of high-sensitivity serum troponin T(12 weeks)
- Concentration of postassium(12 weeks)
- Minnesota Heart Failure Quality of Life Questionnaire (LiHFe)(12 weeks)
- Systolic and diastolic blood pressure(12 weeks)
- N terminal pro B type natriuretic peptide (NT-prpBNP)(12 weeks)
- Left atrial volume (LAV)(12 weeks)
- Electrocardiogram(ECG)(12 weeks)
- Estimated glomerular filtration rate(eGFR)(12 weeks)
- Incidence of Angioedema(12 weeks)
- Left ventricular end diastolic volume (LVEDV)(12 weeks)
- The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E')(12 weeks)
- Pulmonary Artery Pressure(12 weeks)
- NYHA functional classification(12 weeks)
- Concentration of alanine aminotransferase or aspartate aminotransferase(12 weeks)
研究者
ShuangXin Liu
Chief Physician
Guangdong Provincial People's Hospital