Clinical trial NCT02970669: Study on the Effects of Sacubitril/Valsartan on Physical Activity and Sleep in Heart Failure With Reduced Ejection Fraction Patients.
Official title: Multicenter, Randomized, Double-blind, Double Dummy, Parallel Group, Active-controlled 8-week Study and 8-week Open Label Extension to Evaluate the Effect of Initiation of Sacubitril/Valsartan on Objective Measures of Waking Activity and Sleep, as Health-related Quality of Life Functions in Subjects With Heart Failure and Reduced Ejection Fraction (AWAKE-HF).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure, Reduced Ejection Fraction
Keywords: Heart failure with reduced left ventricular ejection fraction (LVEF)
Cardiac dysfunction
Heart muscle dysfunction
Left ventricular (LV) dilation
Left ventricular hypertrophy
HF
AHF
CHF
acute heart failure
chronic heart failure
congestive heart failure
congestive cardiac failure
Heart failure
HReEF
Physical Activity
Actigraphy
Home sleep test
wake
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-11-22
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study was to investigate the effects of initiation of sacubitril/valsartan vs enalapril treatment on objective measures of both waking activity and sleep in subjects with heart failure with reduced ejection fraction.


Eligibility criteria: Key Inclusion Criteria:

* Written informed consent must be obtained before any assessment is performed.
* Men and women between 18 and 80 years of age
* Subjects diagnosed with NYHA class II or III heart failure and with reduced ejection (HFrEF).

(Reduced ejection is defined as left ventricular EF ≤ 40%. LVEF ≤40% may be determined via any local measurement within the past 6 months prior to signing consent, using echocardiography, multi gated acquisition scan (MUGA), CT scanning, MRI or ventricular angiography provided no subsequent study documenting an EF of \>40%. If the EF measurement is expressed as a value range, the average of the range endpoint values should be used as the EF).

* Subjects must be a candidate for treatment with sacubitril/valsartan as per USPI.
* Subjects must be living in a traditional residence, apartment, or non-communal adult home where they can move about freely and frequently and are primarily responsible for scheduling their sleep and daily activities.

Key Exclusion Criteria:

* Subjects with a history of hypersensitivity to any of the study drugs, including history of hypersensitivity to drugs of similar chemical classes, or allergy to ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs.
* Subjects with a history of angioedema drug related or otherwise
* Subjects with symptomatic hypotension or systolic blood pressure \<100 mmHg at screening or \<95 mmHg at randomization
* Subjects with any conditions in skin or upper extremities which would limit the ability to tolerate a wrist-worn actigraphy device on the non-dominant arm for 24 hours/day for the duration of the study.
* Subjects who are non-ambulatory or use mobility assistive devices such as motorized devices, wheelchairs, or walkers. The use of canes for stability while ambulating is acceptable.
* Subjects with physical activity impairment primarily due to conditions other than heart failure such as:
* Exertional angina inflammatory or degenerative joint disease -gout
* peripheral vascular disease
* neurologic disease affecting activity or mobility

Primary outcomes:
measure: Ratio of Mean Activity Counts Collected During the Most Active 30 Minutes of the Subject's Day Between Week 8 and Baseline
timeFrame: Baseline, week 8
Secondary outcomes:
measure: Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 1
timeFrame: Baseline, Week 1
measure: Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 9 and 16
timeFrame: Baseline (Sacubitril/Valsartan: week -1/ Enalapril: week 8), week 9 and 16
measure: Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 8
timeFrame: Baseline, Week 8
measure: Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 1
timeFrame: Baseline, Week 1
measure: Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 9 and 16
timeFrame: Baseline (Sacubitril/Valsartan: week -1 / Enalapril: week 8), week 9 and 16
Other outcomes:
Locations:
city: Fort Payne
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Stockton
country: United States
facility: Novartis Investigative Site
state: California
city: West Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Doral
country: United States
facility: Novartis Investigative Site
state: Florida
city: Inverness
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ormond Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Port Orange
country: United States
facility: Novartis Investigative Site
state: Florida
city: Lutherville
country: United States
facility: Novartis Investigative Site
state: Maryland
city: East Brunswick
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Ridgewood
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Columbia
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Greenville
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Lancaster
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Allen
country: United States
facility: Novartis Investigative Site
state: Texas
city: McKinney
country: United States
facility: Novartis Investigative Site
state: Texas
city: New Braunfels
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Marcos
country: United States
facility: Novartis Investigative Site
state: Texas
city: Sherman
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tomball
country: United States
facility: Novartis Investigative Site
state: Texas
city: Midlothian
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Khandwalla RM, Grant D, Birkeland K, Heywood JT, Fombu E, Owens RL, Steinhubl SR; AWAKE-H. F. Study Investigators. The AWAKE-HF Study: Sacubitril/Valsartan Impact on Daily Physical Activity and Sleep in Heart Failure. Am J Cardiovasc Drugs. 2021 Mar;21(2):241-254. doi: 10.1007/s40256-020-00440-y. Epub 2020 Sep 26.