randOmized stUdy using acceleromeTry to compare Sacubitril/valsarTan and Enalapril in Patients with Heart Failure (OUTSTEP-HF)

• Register: EUCTR
• Last refreshed on: 19 November 2018
• Main ID: EUCTR2016-003085-32-GR
• Date of registration: 17/03/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• 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 - OUTSTEP-HF
• Date of first enrolment: 05/05/2017
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003085-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Iceland, Latvia, Lithuania, Netherlands, Spain, Sweden

Contacts

• Name: GenMeds/ICRO: Veronique Schaaf
• Affiliation: Novartis (Hellas) S.A.C.I.

• Name: GenMeds/ICRO: Veronique Schaaf
• Affiliation: Novartis (Hellas) S.A.C.I.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

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 nondominant arm.
- Patients with any skin or other condition of the nondominant 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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Heart Failure with reduced ejection fraction (HFrEF)
MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Entresto
Product Name: LCZ696 50 mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril / valsartan
Other descriptive name: SACUBITRIL VALSARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Entresto
Product Name: LCZ696 100 mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril / valsartan
Other descriptive name: SACUBITRIL VALSARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Entresto
Product Name: LCZ696 200 mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril / valsartan
Other descriptive name: SACUBITRIL VALSARTAN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Enalapril
Product Name: Enalapril 2.5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: enalapril
Other descriptive name: ENALAPRIL MALEATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: EnaHEXAL
Product Name: Enalapril 5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: enalapril
Other descriptive name: ENALAPRIL MALEATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: EnaHEXAL
Product Name: Enalapril 10 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: enalapril
Other descriptive name: ENALAPRIL MALEATE
C

Primary Outcome(s)

Secondary Objective: - compare the proportion of patients with improved performance (= 30m in the 6MWT between sacubitril/valsartan vs. enalapril (wks 0 to 12).
- demonstrate that sacubitril/valsartan is superior in improving exercise capacity as assessed by 6MWT at wk 12 in a subset of patients with baseline 6min walk distance equal to or less than 300 meters and in between 100-450 meters
- compare the effects of sacubitril/valsartan vs. enalapril on patients' symptom progression by means of the Patient Global Assessment questionnaire
- assess dynamics of changes from baseline in daily non-sedentary daytime physical activity in sacubitril/valsartan vs. enalapril treated patients in wkly and 2-wkly intervals.
- To assess changes from baseline:
- in mean daily non-sedentary daytime physical activity classified by its intensity for sacubitril/valsartan vs. enalapril treated patients (at wk 4, 8, 12) and (wk 0 to 12)
- on M6min after 4, 8, 12 wks and in exercise capacity in the 6MWT at wk 4, 8,12.

Primary end point(s): Change from baseline in 6-minute walking test

Change from baseline in mean daily non-sedentary daytime activity between baseline and end of study

Main Objective: To elucidate the change in physical activity as assessed by the distance walked in meters during the 6-minute walk test between baseline and 12 weeks of study drug treatment in sacubitril/valsartan vs. enalapril patients.

To assess changes in daily non-sedentary daytime activity between baseline and after 12 weeks of treatment in sacubitril/valsartan vs. enalapril treated patients.

Timepoint(s) of evaluation of this end point: Bseline (week 0, at randomization) and week 12

Baseline (week -2 to Week 0), last 14 days of treatment (week 10 to week 12)

Secondary Outcome(s)

Secondary end point(s): 1)Proportion of patients with improved performance (= 30m) in the 6-
minute walking test
2) Proportion of patients with improved performance (= 30m) in the 6-
minute walking test and which walked equal to or less than 300 meters
at baseline
3) Proportion of patients with improved performance (= 30m) in the 6-
minute walking test and which walked 100-450 meters at baseline
4) Change from baseline in 6-minute walking test
5) Proportion of patients who show increased levels (= 10% increase) of
non-sedentary daytime physical activity at week 12 compared to
baseline
6) Percentage of patients with improved symptoms of heart failure as
assessed by patient's Global Assessment
7) Change from baseline in mean daily non sedentary daytime activity in
weekly and two-weekly intervals
8) Change from baseline in mean daily nonsedentary daytime physical
activity classified by its intensity
9) Total weekly time spent in nonsedentary daytime physical activity
10) Total weekly time spent in light nonsedentary daytime physical
activity
11) Total weekly time spent in moderate to vigorous nonsedentary
daytime physical activity
12) Change from baseline in peak six minutes of daytime physical
activity

Timepoint(s) of evaluation of this end point: 1) baseline (week 0, at randomization) and week 12
2) baseline (week 0, at randomization) and week 12
3) baseline (week 0, at randomization) and week 12
4) baseline (week 0, at randomization), treatment (week 4, 8, 12)
5) baseline (week -2 to week 0), end of study 2 (week 10 to week 12)
6) Week 4, 8, 12
7) baseline1 (week -2 to week 0 for two-weekly intervals or last 7 days
prior to randomization for comparison of weekly intervals), weekly or 2-
weekly
from week 0 to week 12.
8) Baseline (week - 2 to week 0), week 2 to week 4, week 6 to week 8,
week 10 to week 12
9) week 0 to week 12 in weekly intervals
10)week 0 to week 12 in weekly intervals
11) week 0 to week 12 in weekly intervals
12) Baseline (week -2 to week 0), week 2 to week 4, week 6 to week 8,
week 10 to week 12

Secondary ID(s)

CLCZ696B3301

2016-003085-32-DE

Source(s) of Monetary Support

Novartis Pharma Services AG