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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02900378
• Date of registration: 09/09/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: randOmized stUdy Using acceleromeTry to Compare Sacubitril/valsarTan and Enalapril in Patients With Heart Failure OUTSTEP-HF
• Scientific title: 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
• Date of first enrolment: December 20, 2016
• Target sample size: 621
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02900378
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Belgium, Bulgaria, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Iceland, Ireland, Latvia, Lithuania, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Heart Failure With Reduced Ejection Fraction

Intervention(s)

Drug: Placebo of LCZ696 (Sacubitril/Valsartan)

Drug: Enalapril

Drug: Placebo of Enalapril

Drug: LCZ696 (Sacubitril/Valsartan)

Primary Outcome(s)

Change From Baseline (Week 0) in Mean Daily Non-sedentary Daytime Activity at End of Study (Week 12) [Time Frame: Baseline, Week 12]

Change From Baseline (Week 0) in the Six Minute Walk Test (6MWT) at End of Study (Week 12) [Time Frame: Baseline, Week 12]

Secondary Outcome(s)

Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Two-weekly Intervals [Time Frame: 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]

Number and Percentage of Participants With Improved Performance (>= 30 m) in the Six Minute Walk Test (6MWT) - FAS [Time Frame: Baseline, Week 12]

Change From Baseline in Mean Daily Non-sedentary Daytime Activity in Weekly Intervals [Time Frame: 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 Six Minute Walk Test (6MWT) - FAS Subset Without AE/SAE [Time Frame: Baseline, Week 12]

Number and Percentage of Participants Achieving PGA Score at Weeks 4, 8 and 12 [Time Frame: Week 4, Week 8, 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 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 Moderate-to-Vigorous Non-sedentary Daytime Physical Activity [Time Frame: 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 [Time Frame: Baseline, Week 12]

Number and Percentage of Participants Who Show Increased Levels (>= 10% Increase) of Non Sedentary Daytime Physical Activity at Week 12 Compared to Baseline [Time Frame: Baseline, Week 12]

Total Weekly Time Spent in Light Non-sedentary Daytime Physical Activity [Time Frame: 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 [Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 and Week 12]

Total Weekly Time Spent in Non-sedentary Daytime Physical Activity [Time Frame: 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 [Time Frame: Baseline, Week 12]

Total Weekly Time Spent in Moderate-to-Vigorous Non-sedentary Daytime Physical Activity [Time Frame: 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 (Week 0) in the Six Minute Walk Test (6MWT) at Weeks 4 and 8 [Time Frame: Baseline, Week 4 and Week 8]

Change From Baseline in Mean Daily Light Non-sedentary Daytime Physical Activity [Time Frame: 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 100-450 Meters at Baseline - FAS Subset Without AE/SAE [Time Frame: Baseline, Week 12]

Secondary ID(s)

CLCZ696B3301

2016-003085-32

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/09/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02900378