Primary:- To elucidate the change in physical activity as assessed by the distance walked in meters during the 6-minute walk test between baseline and 12weeks of study drug treatment in sacubitril/valsartan vs. enalapril patients.- To assess changes…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Change from baseline in 6-minute walking test.
- To assess changes in daily non-sedentary daytime activity between baseline
and after 12 weeks of treatment in sacubitril/valsartan vs. enalapril treated
patients.
Secondary outcome
To compare the proportion of patients with improved performance (* 30m in the
6MWT between sacubitril/valsartan vs. enalapril (wks 0 to 12).
To 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
To compare the effects of sacubitril/valsartan vs. enalapril on patients
symptom progression by means of the Patient Global Assessment (PGA)
questionnaire at week 4, week 8 and week12.
To assess dynamics of changes from baseline1 in daily non-sedentary daytime
physical activity in sacubitril/valsartan vs. enalapril treated patients in
weekly and two-weekly intervals.
To assess changes from baseline 1 in mean daily non-sedentary daytime physical
activity classified by its intensity for sacubitril/valsartan vs. enalapril
treated patients after week 4, week 8 and week12.
To assess the difference in non-sedentary daytime physical activity between
sacubitril/valsartan vs. enalapril treated patients during the treatment period
(weeks 0-12).
To assess changes from baseline1 on M6min (an actigraphy-based measure of the
peak six minutes of daytime physical activity) in sacubitril/valsartan vs.
enalapril treated patients after week 4; week 8 and week 12.
To assess changes from baseline (week 0) in exercise capacity assessed by means
of the 6-minute walking test at weeks 4, 8 and 12.
Background summary
LCZ696 is a medicine which has been approved for the treatment of people with
chronic heart failure (NYHA Class II- IV) and reduced ejection fraction. To
date, over 17,000 subjects have taken LCZ696 in studies that have been
performed in healthy subjects and patients with hypertension, heart failure
with reduced ejection fraction, and heart failure with preserve ejection
fraction.
The other medicine in this study is enalapril which is currently available on
the market and approved for the treatment of patients with clinical signs of
congestive heart failure. Enalapril belongs to a class of medications called
angiotensin-converting enzyme inhibitors, or ACE inhibitors, recommended as
standard-of- care to treat the post-AMI patients.
The purpose of this randomized, actively controlled, double-blind study with
prospective datacollection is to assess differences between
sacubitril/valsartan versus enalapril in increasing non-sedentary daytime
physical activity in HFrEF patients.
Study objective
Primary:
- 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 after12 weeks of treatment in sacubitril/valsartan vs. enalapril treated
patients.
Study design
This is an international (European), randomized, actively controlled,
double-blind, doubledummy, interventional study with prospective
datacollection. The study comprises 6 visits over 14 weeks. Adult patients with
symptomatic HFrEF (NYHA classes II or III/IV at a 1:1
ratio, see Section 5.3) managed in an ambulatory setting (i.e. by primary care
physicians, office based cardiologists, HF outpatient clinics) will be
randomized in a 1:1 allocation to receive sacubitril/valsartan or enalapril
during the double-blind period. Actigraphy will be performed during the entire
duration of the study by means of a wrist -worn accelerometry device; the
device will be worn continuously for two weeks prior to randomization in order
to obtain an individual baseline for each patient, and throughout the treatment
period of the study (12 weeks).
Intervention
Treatment with LCZ696 (sacubitril/valsartan) or enalapril.
Study burden and risks
Risks: Side effects of study medication and burden assessments.
Total treatment:
- Physical examination 6x
- Vital signs 6x
- Blood tests 6x, when investigator deems necessary.
- Urine examination (pregnancy test) 2x
- Questionnaires 5x
- 6 Minute Walking Test 4x
- Determination NYHAclass 6x
- Measure length/weight 1x
- ECG, in case not doen within 4 months before screening.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
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.
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003085-32-NL |
| ClinicalTrials.gov | NCT02900378 |
| CCMO | NL60273.100.17 |