randOmized stUdy Using acceleromeTry to Compare Sacubitril/valsarTan and Enalapril in Patients With Heart Failure

Novartis Pharmaceuticals621 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

621

Conditions

Chronic Heart Failure With Reduced Ejection Fraction

Interventions

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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. Key Exclusion Criteria: * 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 - 2. * 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.

Locations (119)

Novartis Investigative Site

Edegem, Antwerpen, Belgium

Novartis Investigative Site

Dendermonde, Belgium

Novartis Investigative Site

Geel, Belgium

Novartis Investigative Site

Ghent, Belgium

Novartis Investigative Site

Turnhout, Belgium

Novartis Investigative Site

Outcomes

Primary Outcomes

Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (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.

Time frame: Baseline, Week 12

Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (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).

Time frame: Baseline, Week 12

Secondary Outcomes

Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS

The proportion of patients with improved performance (\>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group.

Time frame: 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

The proportion of patients with improved performance (\>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group.

Time frame: 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

The proportion of patients with improved performance (\>= 30 meters) in the six-minute walk test (6MWT) was assessed by treatment group in a subset of patients with baseline six-minute walk distance equal to or less than 300 meters.

Time frame: 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 Subset Without AE/SAE

Time frame: Baseline, Week 12

Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS

Time frame: Baseline, Week 12

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

Time frame: Baseline, Week 12

Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8

The impact of LCZ696 (Sacubitril/Valsartan) and Enalapril on functional exercise capacity was measured by the Six Minute Walk Test at Weeks 4 and 8. 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.

Time frame: 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

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 will be calculated over 14 days before randomization (baseline) and the last 14 days of treatment (i.e week 10 to week 12)

Time frame: Baseline, Week 12

Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12

The Patient Global Assessment (PGA) is a self-reported tool to assess the patients' subjective rating of their disease activity widely used in HF research. The patients are asked to report functioning or response to an intervention by rating their current condition compared to their pre-intervention condition on a numerical scale: 1) much improved 2) moderately improved 3) a little improved 4) unchanged 5) a little worse 6) moderately worse or 7) much worse.

Time frame: Week 4, Week 8, Week 12

Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA)

Time frame: Week 4, Week 8, Week 12

Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals

Non-sedentary physical activity is defined as \>= 178.50 activity counts per minute; Mean daily non-sedentary daytime physical activity were being calculated over weekly and compared to before the inclusion.