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Phase 3 Completed N=621 Randomized Triple-blind Treatment

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

Chronic Heart Failure With Reduced Ejection Fraction
Source: ClinicalTrials.gov NCT02900378 ↗
Enrolled (actual)
621
Serious AEs
7.6%
Results posted
Sep 2019
Primary outcomePrimary: Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) — 365.37; 371.08; 395.80; 395.33 meters — p=0.2464
◆ Published Evidence
No publication linked

No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.

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).

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12)
365.37; 371.08; 395.80; 395.33; 31.57; 24.89 0.2464
PRIMARY
Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12)
510.11; 506.81; 479.69; 487.53; -30.42; -19.28 0.4769
SECONDARY
Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS
142; 153; 149; 129; 11; 20
SECONDARY
Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE
133; 146; 149; 129; 8; 19
SECONDARY
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
35; 31; 41; 29; 2; 5
SECONDARY
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
33; 30; 41; 29; 1; 4
SECONDARY
Number and Percentage of Participants With Improved Performance (>= 30 m) in the 6MWT Which Walked 100-450 Meters at Baseline - FAS
109; 121; 122; 105; 7; 12
SECONDARY
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
103; 115; 122; 105; 5; 11
SECONDARY
Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8
365.37; 371.08; 385.22; 385.02; 19.13; 13.72 0.1814
SECONDARY
Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline
175; 163; 28; 31; 99; 108
SECONDARY
Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12
19; 16; 63; 51; 94; 64 0.0516
SECONDARY
Number and Percentage of Participants With Improved Symptoms of Heart Failure as Assessed by Patient Global Assessment (PGA)
176; 131; 98; 131; 17; 21 0.0029 sig
SECONDARY
Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals
512.07; 505.31; 527.34; 509.28; 22.60; 9.88 0.0008 sig
SECONDARY
Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals
512.07; 505.31; 529.63; 509.02; 22.88; 8.06 0.0001 sig
SECONDARY
Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity
251.94; 247.30; 263.17; 251.37; 14.10; 6.28 0.0004 sig
SECONDARY
Change From Baseline in Mean Daily Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
260.13; 258.01; 264.16; 257.92; 8.50; 3.60 0.0854
SECONDARY
Total Weekly Time Spent in Non-sedentary Daytime Physical Activity
3616.87; 3528.56; 3676.46; 3560.10; 103.29; 82.48 0.0065 sig
SECONDARY
Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity
1773.14; 1721.50; 1834.71; 1757.76; 81.84; 53.74 0.0061 sig
SECONDARY
Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity
1843.73; 1807.07; 1841.76; 1802.34; 21.45; 28.75 0.3231
SECONDARY
Change From Baseline in Peak Six Minutes of Daytime Physical Activity
189.08; 182.52; 193.54; 184.46; 6.18; 3.52 0.4525

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02900378). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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