A Multi-center, Prospective, Randomized, Double-blind Study to Assess the Impact of Sacubitril/Valsartan vs. Enalapril on Daily Physical Activity Using a Wrist Worn Actigraphy Device in Adult Chronic Heart Failure Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 621
- 试验地点
- 1
- 主要终点
- Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12)
研究概览
简要总结
The purpose of this randomized, actively controlled, double-blind study with prospective data collection was to assess differences between sacubitril/valsartan versus enalapril in increasing exercise capacity and non-sedentary physical activity in HFrEF patients. Physical activity was assessed by the 6 minute walk test, and daily physical activity was continuously measured by means of a wrist-worn accelerometry device from 2 weeks before until 12 weeks after start of study therapy (sacubitril/valsartan or enalapril).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent obtained before any study assessment is performed.
- •Ambulatory ≥ 18 years of age with a diagnosis of chronic symptomatic HF (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 40%
- •AND one of the following two criteria:
- •Plasma NT-proBNP level of ≥ 300 pg/mL or BNP ≥ 100 pg/mL (measurement may be recorded no longer than past 12 months) OR
- •Confirmation of a heart failure hospitalization last 12 months.
- •Patients must be on stable HF medication for at least 4 weeks prior to Week - 2, where the minimal daily dose of current evidence based therapies is equivalent to at least 2.5 mg/d enalapril
- •Willingness to wear the accelerometer wristband continuously for the duration of the trial.
- •Patients must be living in a setting, allowing them to move about freely and where they are primarily self-responsible for scheduling their sleep and daily activities.
排除标准
- •History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes
- •Use of sacubitril/valsartan prior to week -
- •Bedridden patients, or patients with significantly impaired/limited physical activity and/or fatigue due to medical conditions other than HF, such as, but not limited to angina (chest pain at exertion), arthritis, gout, peripheral artery occlusive disease, obstructive or restrictive lung disease, malignant disease, neurological disorders (e.g. Parkinson's or Alzheimer's disease, central and peripheral neuroinflammatory and -degenerative disorders or functional central nervous lesions due to hemodynamic or traumatic incidents), injuries (incl. diabetic foot ulcers) or missing limbs
- •Patients with palsy, tremor or rigor affecting the non-dominant arm.
- •Patients with any skin or other condition of the non-dominant arm that would limit the ability to wear the actigraphy device continuously (24h/day) over 14 weeks.
- •Patients fully depending on a mobility support system, e.g. wheelchair, scooter or walker. Patients are allowed to use a cane as long as this is not used with the non-dominant arm.
研究组 & 干预措施
LCZ696 (Sacubitril/Valsartan)
After randomization, patients in this arm received LCZ696 (Sacubitril/Valsartan) twice daily and matching placebo of Enalapril depending on the patient's previous ACEI/ARB dose (enalapril equivalent dose) for 2 weeks. Patients could start study medication at dose level 1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ) or matching placebo bid. After 2 weeks (visit 3) the doses were up-titrated: patients, who started on dose level 2 or 2a received the target dose of study medication (level 3) at this point. After another 2 weeks (visit 4) all patients were to achieve the target dose of 97 mg/103 mg bid LCZ696(sacubitril/valsartan) and matching placebo, provided no safety and tolerability issues arised during uptitration.
干预措施: LCZ696 (Sacubitril/Valsartan) (Drug)
LCZ696 (Sacubitril/Valsartan)
After randomization, patients in this arm received LCZ696 (Sacubitril/Valsartan) twice daily and matching placebo of Enalapril depending on the patient's previous ACEI/ARB dose (enalapril equivalent dose) for 2 weeks. Patients could start study medication at dose level 1 (24 mg/26 mg LCZ), 2 (49 mg/51 mg LCZ) or 2a (49 mg/51 mg LCZ) or matching placebo bid. After 2 weeks (visit 3) the doses were up-titrated: patients, who started on dose level 2 or 2a received the target dose of study medication (level 3) at this point. After another 2 weeks (visit 4) all patients were to achieve the target dose of 97 mg/103 mg bid LCZ696(sacubitril/valsartan) and matching placebo, provided no safety and tolerability issues arised during uptitration.
干预措施: Placebo of Enalapril (Drug)
Enalapril
After randomization, patients in this arm received Enalapril twice daily and matching placebo of LCZ696 (Sacubitril/Valsartan) depending on the patient's previous ACEI/ARB for 2 weeks. Patients could start study medication at dose level 1 or 2a or matching placebo bid. After 2 weeks (visit 3) the doses were up-titrated: patients, who started on dose level 2 or 2a received the target dose of study medication (level 3) at this point. After another 2 weeks (visit 4) all patients were to achieve the target dose of 10 mg bid enalapril and matching placebo, provided no safety and tolerability issues arised during uptitration
干预措施: Placebo of LCZ696 (Sacubitril/Valsartan) (Drug)
Enalapril
After randomization, patients in this arm received Enalapril twice daily and matching placebo of LCZ696 (Sacubitril/Valsartan) depending on the patient's previous ACEI/ARB for 2 weeks. Patients could start study medication at dose level 1 or 2a or matching placebo bid. After 2 weeks (visit 3) the doses were up-titrated: patients, who started on dose level 2 or 2a received the target dose of study medication (level 3) at this point. After another 2 weeks (visit 4) all patients were to achieve the target dose of 10 mg bid enalapril and matching placebo, provided no safety and tolerability issues arised during uptitration
干预措施: Enalapril (Drug)
结局指标
主要结局
Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12)
时间窗: Baseline, Week 12
Non-sedentary physical activity is defined as \>= 178.50 activity counts per minute; the average number of minutes per day spent in non-sedentary physical activity is being calculated over 14 days before randomization (baseline i.e. week -2 to week 0) and the last 14 days of treatment (i.e. week 10 to week 12).
Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12)
时间窗: Baseline, Week 12
The impact of LCZ696 (Sacubitril/Valsartan) and Enalapril on functional exercise capacity was measured by the Six Minute Walk Test at 12 weeks. The 6MWT measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway.
次要结局
- Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS Subset Without AE/SAE(Baseline, Week 12)
- Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA)(Week 4, Week 8, Week 12)
- Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12)
- Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked Equal to or Less Than 300 Meters at Baseline - FAS Subset Without AE/SAE(Baseline, Week 12)
- Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS(Baseline, Week 12)
- Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS(Baseline, Week 12)
- Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE(Baseline, Week 12)
- Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked Equal to or Less Than 300 Meters at Baseline - FAS(Baseline, Week 12)
- Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals(Baseline, Weeks 0 to 2, Weeks 2 to 4, Weeks 4 to 6, Weeks 6 to 8, Weeks 8 to 10, Weeks 10 to 12)
- Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8(Baseline, Week 4 and Week 8)
- Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline(Baseline, Week 12)
- Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12(Week 4, Week 8, Week 12)
- Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12)
- Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12)
- Total Weekly Time Spent in Non-sedentary Daytime Physical Activity(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12)
- Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12)
- Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity(Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12)
- Change From Baseline in Peak Six Minutes of Daytime Physical Activity(Baseline, Week 2, Week 4, Week 6, Week 8 and Week 12)