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

October 6, 2021 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Phase 4

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Fort Payne, Alabama, United States, 35967
        • Novartis Investigative Site
    • California
      • Beverly Hills, California, United States, 90211
        • Novartis Investigative Site
      • Stockton, California, United States, 95204
        • Novartis Investigative Site
      • West Hills, California, United States, 91307
        • Novartis Investigative Site
    • Florida
      • Doral, Florida, United States, 33126
        • Novartis Investigative Site
      • Inverness, Florida, United States, 34452
        • Novartis Investigative Site
      • Ormond Beach, Florida, United States, 32174
        • Novartis Investigative Site
      • Port Orange, Florida, United States, 32127
        • Novartis Investigative Site
    • Maryland
      • Lutherville, Maryland, United States, 21093
        • Novartis Investigative Site
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Novartis Investigative Site
      • Ridgewood, New Jersey, United States, 07450
        • Novartis Investigative Site
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Novartis Investigative Site
      • Greenville, South Carolina, United States, 29615
        • Novartis Investigative Site
      • Lancaster, South Carolina, United States, 29720
        • Novartis Investigative Site
    • Texas
      • Allen, Texas, United States, 75002-3688
        • Novartis Investigative Site
      • McKinney, Texas, United States, 75013
        • Novartis Investigative Site
      • New Braunfels, Texas, United States, 78130
        • Novartis Investigative Site
      • San Antonio, Texas, United States, 78229
        • Novartis Investigative Site
      • San Marcos, Texas, United States, 78666
        • Novartis Investigative Site
      • Sherman, Texas, United States, 75092
        • Novartis Investigative Site
      • Tomball, Texas, United States, 77375
        • Novartis Investigative Site
    • Virginia
      • Midlothian, Virginia, United States, 23114
        • Novartis Investigative Site
    • Washington
      • Tacoma, Washington, United States, 98405
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Enalapril

Double blind treatment epoch: Patients randomized to this arm received 1 tablet of enalapril and 1 tablet of matching placebo sacubitril/valsartan twice daily for 8 weeks. All Patients began the study on Dose Level 1 (i.e. 2.5 mg enalapril BID). Patients may have been sequentially up-titrated to achieve desired dose of Dose Level 3 (i.e. 10 mg enalapril BID). Patients not tolerating dose escalation could have been titrated down to next lower dose level.

Open-label treatment epoch: All patients entering this epoch (8 weeks) were given sacubitril/valsartan 49/51 mg BID (Dose Level 2) unless they completed the double-blind treatment epoch on enalapril Dose Level 1. Instead, these patients entered open-label epoch on Dose Level 1 of sacubitril/valsartan. Patients may have been sequentially up-titrated to achieve desired dose of Dose Level 3 of sacubitril/valsartan. Patients not tolerating dose escalation could have been titrated down to next lower dose level.
Drug: sacubitril/valsartan (LCZ696)
sacubitril/valsartan tablet taken orally.
Drug: enalapril
Enalapril tablet taken orally.
Drug: matching placebo sacubitril/valsartan (LCZ696)
matching placebo sacubitril/valsartan tablet taken orally
EXPERIMENTAL: Sacubitril/Valsartan

Double blind treatment epoch: Patients randomized to this arm received 1 tablet of sacubitril/valsartan and 1 tablet of matching placebo enalapril twice daily for 8 weeks. All Patients began the study on Dose Level 1 (i.e. 24/26 mg sacubitril/valsartan BID). Patients may have sequentially been up-titrated to achieve desired dose of Dose Level 3 (i.e. 97/103 mg sacubitril/valsartan BID). Patients not tolerating dose escalation could have been titrated down to next lower dose level.

Open-label treatment epoch: All patients entering this epoch (8 weeks) were given sacubitril/valsartan 49/51 mg BID (Dose Level 2) unless they completed the double-blind treatment epoch on Dose Level 1. Instead, these patients entered open-label epoch on Dose Level 1. Patients may sequentially have been up-titrated to achieve desired dose of Dose Level 3. Patients not tolerating dose escalation could have been titrated down to next lower dose level.
Drug: sacubitril/valsartan (LCZ696)
sacubitril/valsartan tablet taken orally.
Drug: matching placebo enalapril
matching placebo enalapril tablet taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ratio of Mean Activity Counts Collected During the Most Active 30 Minutes of the Subject's Day Between Week 8 and Baseline
Time Frame: Baseline, week 8
The primary endpoint is the ratio in mean activity counts collected during the most active 30 minutes of the subject's day between the final randomized treatment phase measurement (mean of endpoint data collected each day during week 8) and baseline phase (mean of endpoint data collected each day during week -1), as measured by wrist-worn accelerometer collected actigraphy (total counts per 30 min period collected during the most active 30 minutes of each day). A ratio > 1 indicates an increase in mean activity counts from baseline to week 8.
Baseline, week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 1
Time Frame: Baseline, Week 1
Change in mean activity counts during most active 30 minutes of day from baseline phase (mean of data collected during week -1) to week 1 (mean of data collected during week 1), as measured by actigraphy (total counts per 30 min period collected during the most active 30 minutes of each day).
Baseline, Week 1
Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 9 and 16
Time Frame: Baseline (Sacubitril/Valsartan: week -1/ Enalapril: week 8), week 9 and 16
Change in mean activity counts during most active 30 minutes of day from baseline phase (mean of data collected during week -1 for Sacubitril/Valsartan and mean of data collected during week 8 for Enalapril) to week 9 and 16 (mean of data collected during weeks 9 and 16), as measured by actigraphy (total counts per 30 min period collected during the most active 30 minutes of each day).
Baseline (Sacubitril/Valsartan: week -1/ Enalapril: week 8), week 9 and 16
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 8
Time Frame: Baseline, Week 8
Change in mean activity (counts per minute) during sleep from baseline phase (mean of data collected during week -1) to the final randomized treatment phase measurement (mean of data collected during week 8), as measured by actigraphy (activity counts per minute during daily sleep period, wrist-worn accelerometer).
Baseline, Week 8
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 1
Time Frame: Baseline, Week 1
Change in mean activity (counts per minute) during sleep from baseline phase (mean of data collected during week -1) to week 1 (mean of data collected during week 1), as measured by actigraphy (activity counts per minute during daily sleep period, wrist-worn accelerometer).
Baseline, Week 1
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 9 and 16
Time Frame: Baseline (Sacubitril/Valsartan: week -1 / Enalapril: week 8), week 9 and 16
Change in mean activity (counts per minute) during sleep from baseline phase (mean of data collected during week -1 for Sacubitril/Valsartan and mean of data collected during week 8 for Enalapril) to week 9 and 16 (mean of data collected during week 9 and 16), as measured by actigraphy (activity counts per minute during daily sleep period, wrist-worn accelerometer).
Baseline (Sacubitril/Valsartan: week -1 / Enalapril: week 8), week 9 and 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 16, 2016

Primary Completion (ACTUAL)

March 19, 2018

Study Completion (ACTUAL)

March 19, 2018

Study Registration Dates

First Submitted

November 17, 2016

First Submitted That Met QC Criteria

November 17, 2016

First Posted (ESTIMATE)

November 22, 2016

Study Record Updates

Last Update Posted (ACTUAL)

October 7, 2021

Last Update Submitted That Met QC Criteria

October 6, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLCZ696BUS14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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