Study on the Effects of Sacubitril/Valsartan on Physical Activity and Sleep in Heart Failure With Reduced Ejection Fraction Patients.

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).

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.

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