183 - AWAKE-HF: Rationale and Design of a Study Using a Wearable Biosensor to Objectively Evaluate the Effect of Sacubitril/Valsartan Initiation on Measures of Physical Activity, Symptoms, and Sleep, as Health-Related Quality of Life Functions in Subjects with Heart Failure

Abstract

Background: Clinical experience suggests that patients with heart failure with reduced ejection fraction (HFrEF) report improved health-related quality of life (HRQoL) shortly after beginning sacubitril/valsartan (S/V). This study explores early changes in objective HRQoL measures (physical activity, sleep) in HFrEF subjects initiating S/V versus enalapril. Methods: AWAKE-HF is a prospective, multicenter, double-blind, randomized trial assessing physical activity during waking and sleeping hours, subjective sleep quality, and HRQoL of approximately 140 HFrEF subjects (LVEF ≤40%, NYHA functional class II-III) in their unrestricted home environment. The 18-week study consists of 3 phases: a 2-week baseline phase during which subjects continue current HF therapy, an 8-week blinded treatment phase (1:1 S/V vs enalapril, uptitrated to target doses), and an 8-week S/V open-label (OL) extension phase. Subjects will wear a wrist-worn actigraphy device continuously during five 7-day assessment periods: baseline phase (2nd week), blinded treatment phase (1st and 8th weeks) and the OL extension (1st and 8th weeks). During each assessment period, subjects also will complete a daily symptom assessment tool and a sleep questionnaire (e-diary), reporting every 24 hours. KCCQ assessments and a home sleep test will be taken during the baseline phase and prior to the end of the randomized and OL phases. The difference between mean activity counts (baseline vs blinded treatment phase) during the most active 30 minutes of the subject's waking hours and mean activity during sleep will be the primary and key secondary endpoints. Additional endpoints include relationships between the initiation of study treatment and various activity measurements, activity temporal distribution, KCCQ scores, sleep disturbances, and apnea-hypopnea index (AHI) during different study periods. Conclusion: AWAKE-HF is an evaluation of the early impact of S/V treatment on HRQoL in the home environment in HFrEF subjects. Clinical implications: The AWAKE-HF study will objectively assess the impact of sacubitril/valsartan treatment initiation vs enalapril on health related quality of life in subjects with HFrEF. This may provide insight and perspective into the early real-world clinical experience with sacubitril/valsartan.