A Randomized, Double-blind, Active-controlled Study to Assess the Effect of LCZ696 Compared With Enalapril to Improve Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 201
- 试验地点
- 1
- 主要终点
- Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 3 Months of Treatment
研究概览
简要总结
The purpose of the study was to determine the effect of LCZ696 vs. enalapril on improvement of exercise capacity in patients with chronic heart failure with reduced ejection fraction.
详细描述
This study was a randomized, double-blind, double-dummy, parallel-group, active-controlled, two-arm trial to compare LCZ696 200 mg twice daily (bid) to enalapril 10 mg bid in improving exercise capacity, daily physical activity and quality of life in patients with stable chronic heart failure (New York Heart Association III) and reduced left ventricular ejection fraction (LVEF ≤ 40%).
The study consisted of a screening period of 2 weeks during which the subject's eligibility for the study was assessed followed by a double blind treatment period of 12 weeks. Eligible subjects were randomized 1:1 to receive either LCZ696 or enalapril during the double-blind period. Treatment was initiated with LCZ696 100 mg bid or enalapril 5 mg bid (enalapril 10 mg bid for patients at a stable daily dose of enalapril above 10 mg per day or corresponding doses of other angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) prior first screening visit), respectively. Dose was up-titrated after 2 weeks to the final dose of LCZ696 200 mg bid or enalapril 10 mg bid.
Patients continued to take their background medications for chronic heart failure during the study, with the exception of ACEI or ARBs which were replaced by investigational treatment and had to be discontinued before first dose of study drug.
The primary objective was to demonstrate the superiority of LCZ696 200 mg bid compared to enalapril 10 mg bid in improving exercise tolerance (peak respiratory oxygen uptake (VO2peak), adjusted to body weight) as assessed by cardio-pulmonary-exercise testing (CPET) in patients with stable chronic heart failure (NYHA III) and reduced ejection fraction (LVEF ≤ 40%) after 3 months treatment.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a diagnosis of chronic heart failure (NYHA class III) and reduced ejection fraction (LVEF ≤ 40%)
- •Reduced ability to exercise, evidenced by VO2peak ≤ 18 ml/min per kg
- •Patients had to be on an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks prior to the screening visit and until randomization visit.
排除标准
- •History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs
- •Previous history of intolerance to recommended target doses of ACEIs or ARBs
- •Known history of angioedema
- •Requirement of treatment with both ACEIs and ARBs
- •Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy)
- •Symptomatic hypotension
- •Impaired renal function
- •Pregnant or nursing (lactating) women
研究组 & 干预措施
LCZ696
LCZ696 100 mg oral twice daily (bid) for 2 weeks followed by LCZ696 200 mg oral bid for 10 weeks.
干预措施: LCZ696 (Drug)
LCZ696
LCZ696 100 mg oral twice daily (bid) for 2 weeks followed by LCZ696 200 mg oral bid for 10 weeks.
干预措施: Placebo matching enalapril (Drug)
Enalapril
Enalapril 5 mg oral twice daily (bid) for 2 weeks followed by enalapril 10 mg oral bid for 10 weeks.
Patients who prior Screening were at a stable daily dose of enalapril above 10 mg per day (or corresponding doses of other ACEI/ARB) started the study at a dose of enalapril 10 mg bid.
干预措施: Enalapril (Drug)
Enalapril
Enalapril 5 mg oral twice daily (bid) for 2 weeks followed by enalapril 10 mg oral bid for 10 weeks.
Patients who prior Screening were at a stable daily dose of enalapril above 10 mg per day (or corresponding doses of other ACEI/ARB) started the study at a dose of enalapril 10 mg bid.
干预措施: Placebo matching LCZ696 (Drug)
结局指标
主要结局
Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 3 Months of Treatment
时间窗: Baseline, 3 months
Cardiopulmonary exercise testing (CPET) is an established method to evaluate the exercise tolerance of heart failure patients by evaluating the cardio-pulmonary system using the measurement of respiratory gases during physical (exercise) stress. One of the parameters attained by this test is the peak respiratory oxygen uptake (VO2peak). CPET to assess VO2peak was performed at a cycle ergometer at baseline (Visit 2, 9 days prior randomization) and after 6 weeks and 3 months of treatment (Visit 6 and Visit 7, respectively). The VO2peak adjusted to body weight was calculated based on the corresponding visit's VO2peak (unadjusted) and body weight data by using the following formula: VO2peak (unadjusted)/body weight. Higher values of VO2peak indicate less symptom severity and therefore a positive change from baseline indicates improvement.
次要结局
- Change From Baseline in Peak Respiratory Oxygen Uptake (VO2peak) Adjusted to Body Weight) After 6 Weeks of Treatment(Baseline, 6 weeks)
- Change From Baseline in the Minute Ventilation (VE) to Carbon Dioxide Output Slope (VE/VCO2 Slope)(Baseline, 6 weeks, 3 months)
- Change From Baseline in Rate of Perceived Exertion (Perceived Dyspnea and Perceived Fatigue) During Exercise Assessed by Borg Scale(Baseline, 3 months)
- Change From Baseline in Exercise Capacity (Watt) at Ventilatory Anaerobic Threshold (VAT)(Baseline, 6 weeks, 3 months)