A 36-week, Randomized, Double-blind, Multi-center, Parallel Group, Active Controlled Study to Evaluate the Efficacy, Safety and Tolerability of LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 307
- 试验地点
- 1
- 主要终点
- Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
研究概览
简要总结
The study will assess the effects of 36 weeks of treatment with LCZ696 compared to valsartan on N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with chronic heart failure and preserved left-ventricular ejection fraction.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with documented stable chronic heart failure (NYHA II-IV):
- •LVEF ≥ 45% (local measurement, assessed by echocardiography, MUGA, CT scan, MRI or ventricular angiography)
- •the ejection fraction must have been obtained within 6 months prior to randomization or after any MI or other event that would affect ejection fraction.
- •Plasma NT-proBNP > 500 pg/ml at Visit
- •Patients with documented stable chronic heart failure (NYHA II-IV).
- •Patients receiving ACE inhibitors (ACEi), an angiotensin receptor blockers (ARB) and/or a beta blockers must be on a stable dose of these medications stable for the 1 month period prior to Visit
- •Patients must be on diuretic therapy prior to Visit 1 (flexible dosing is permitted).
- •Patients with a controlled systolic BP, defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP at randomization (Visit 2).
- •Patients with at least one of the following symptoms at the time of screening (Visit 1):
- •Dyspnea on exertion
- •Orthopnea
- •Paroxysmal nocturnal dyspnea
- •Peripheral edema
- •Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the Modification of Diet in Renal Disease formula).
- •Patients with a potassium ≤5.2 mmol/l at Visit 1.
排除标准
- •Patients with a prior LVEF reading <45%, at any time.
- •Patients who require treatment with both an ACE inhibitor and an ARB.
- •Isolated right heart failure due to pulmonary disease.
- •Dyspnea and/or edema from non-cardiac causes, such as lung disease, anemia, or severe obesity.
- •Presence of hemodynamically significant mitral and /or aortic valve disease.
- •Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
- •Presence of hypertrophic obstructive cardiomyopathy.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
LCZ696
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
干预措施: LCZ696 (Drug)
LCZ696
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
干预措施: Placebo (Drug)
Valsartan
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
干预措施: Valsartan (Drug)
Valsartan
During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
时间窗: Baseline, 12 weeks
Evaluation of NT-proBNP was performed by a central laboratory. Change from baseline in NT-proBNP was presented as a ratio where the ratio was calculated as the NT-proBNP value at 12 weeks over the NT-proBNP value at baseline. A ratio \< 1 indicates improvement.
次要结局
- Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index(Baseline, 36 weeks)
- Change in Echocardiography Parameters: Isovolumic Relaxation Time(Baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity(Baseline, 36 weeks)
- Change From Baseline in Arterial Stiffness Parameters: Heart Rate Correct Cen Aug/Pulse Ht(baseline, 36 weeks)
- Change From Baseline in NT-proBNP and Brain Natriuretic Peptide (BNP)(baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: Left Ventricular Mass(Baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction(Baseline, 36 weeks)
- Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Relative Wall Thickness, Left Atrial Dimension(Baseline, 36 weeks)
- Percentage of Participants With Clinical Composite Assessment of Improved, Unchanged or Worsened(36 weeks)
- Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV(baseline, 36 weeks)
- Change From Baseline in Arterial Stiffness Parameters: Brachial Systolic Blood Pressure (SBP), Brachial Diastolic Blood Pressure (DBP), Central Augmentation Pressure, Central Pressure at T1-DP, Central SBP, Central DBP, Central Mean Pressure(baseline, 36 weeks)
- Change From Baseline in Plasma Cyclic Guanine Monophosphate (cGMP)(baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume(Baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus(Baseline, 36 weeks)
- Change From Baseline in Albumin/Creatinine Ratio(baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index(Baseline, 36 weeks)
- Change From Baseline in Arterial Stiffness Parameters: Heart Rate(baseline, 36 weeks)
- Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio(Baseline, 36 weeks)
- Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and Individual Domain Summary Scores(baseline, 36 weeks)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)(baseline, 36 weeks)
- Change From Baseline in Serum Creatinine(baseline, 36 weeks)
- Change From Baseline in Arterial Stiffness Parameters: Pulse Wave Velocity(baseline, 36 weeks)
- Change From Baseline in Sitting SBP, Sitting DBP and Sitting Pulse Pressure (PP)(baseline, 36 weeks)