randOmized stUdy Using acceleromeTry to Compare Sacubitril/valsarTan and Enalapril in Patients With Heart Failure
Condition: Chronic Heart Failure With Reduced Ejection Fraction
MeSH terms: Heart Failure
Intervention: LCZ696 (Sacubitril/Valsartan); Placebo of LCZ696 (Sacubitril/Valsartan); Enalapril; Placebo of Enalapril
Intervention description: LCZ696 (sacubitril/valsartan) was available in 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets; Placebo of LCZ696 (sacubitril/valsartan) was available to match 24 mg/26 mg, 49 mg/51 and 97 mg/103 mg mg film-coated tablets; Enalapril was available in 2.5 mg, 5 mg and 10 mg film-coated tablets; Placebo of Enalapril was available to match 2.5 mg, 5 mg and 10 mg film-coated tablets
Intervention MeSH terms: Valsartan; Enalapril; Enalaprilat; Sacubitril and valsartan sodium hydrate drug combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 621.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: sacubitril/valsartan; enalapril; physical activity; actigraphy; sleep; heart failure; reduced ejection fraction; randomized controlled trial; accelerometry

Summary:

      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).
    

Eligibility criteria:

        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.