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

Primary Purpose

Heart Failure, Reduced Ejection Fraction

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
sacubitril/valsartan (LCZ696)
enalapril
matching placebo sacubitril/valsartan (LCZ696)
matching placebo enalapril
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Heart Failure, Reduced Ejection Fraction focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Enalapril

Sacubitril/Valsartan

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Ratio of Mean Activity Counts Collected During the Most Active 30 Minutes of the Subject's Day Between Week 8 and Baseline
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.

Secondary Outcome Measures

Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to 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).
Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to 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).
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to 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).
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to 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).
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to 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).

Full Information

First Posted
November 17, 2016
Last Updated
October 6, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02970669
Brief Title
Study on the Effects of Sacubitril/Valsartan on Physical Activity and Sleep in Heart Failure With Reduced Ejection Fraction Patients.
Acronym
AWAKE-HF
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

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
December 16, 2016 (Actual)
Primary Completion Date
March 19, 2018 (Actual)
Study Completion Date
March 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Enalapril
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Sacubitril/Valsartan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
sacubitril/valsartan (LCZ696)
Intervention Description
sacubitril/valsartan tablet taken orally.
Intervention Type
Drug
Intervention Name(s)
enalapril
Intervention Description
Enalapril tablet taken orally.
Intervention Type
Drug
Intervention Name(s)
matching placebo sacubitril/valsartan (LCZ696)
Intervention Description
matching placebo sacubitril/valsartan tablet taken orally
Intervention Type
Drug
Intervention Name(s)
matching placebo enalapril
Intervention Description
matching placebo enalapril tablet taken orally
Primary Outcome Measure Information:
Title
Ratio of Mean Activity Counts Collected During the Most Active 30 Minutes of the Subject's Day Between Week 8 and Baseline
Description
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.
Time Frame
Baseline, week 8
Secondary Outcome Measure Information:
Title
Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 1
Description
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).
Time Frame
Baseline, Week 1
Title
Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 9 and 16
Description
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).
Time Frame
Baseline (Sacubitril/Valsartan: week -1/ Enalapril: week 8), week 9 and 16
Title
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 8
Description
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).
Time Frame
Baseline, Week 8
Title
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 1
Description
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).
Time Frame
Baseline, Week 1
Title
Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 9 and 16
Description
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).
Time Frame
Baseline (Sacubitril/Valsartan: week -1 / Enalapril: week 8), week 9 and 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Fort Payne
State/Province
Alabama
ZIP/Postal Code
35967
Country
United States
Facility Name
Novartis Investigative Site
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Novartis Investigative Site
City
Stockton
State/Province
California
ZIP/Postal Code
95204
Country
United States
Facility Name
Novartis Investigative Site
City
West Hills
State/Province
California
ZIP/Postal Code
91307
Country
United States
Facility Name
Novartis Investigative Site
City
Doral
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Novartis Investigative Site
City
Inverness
State/Province
Florida
ZIP/Postal Code
34452
Country
United States
Facility Name
Novartis Investigative Site
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Novartis Investigative Site
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Novartis Investigative Site
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
Facility Name
Novartis Investigative Site
City
East Brunswick
State/Province
New Jersey
ZIP/Postal Code
08816
Country
United States
Facility Name
Novartis Investigative Site
City
Ridgewood
State/Province
New Jersey
ZIP/Postal Code
07450
Country
United States
Facility Name
Novartis Investigative Site
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Novartis Investigative Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Novartis Investigative Site
City
Lancaster
State/Province
South Carolina
ZIP/Postal Code
29720
Country
United States
Facility Name
Novartis Investigative Site
City
Allen
State/Province
Texas
ZIP/Postal Code
75002-3688
Country
United States
Facility Name
Novartis Investigative Site
City
McKinney
State/Province
Texas
ZIP/Postal Code
75013
Country
United States
Facility Name
Novartis Investigative Site
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78130
Country
United States
Facility Name
Novartis Investigative Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Novartis Investigative Site
City
San Marcos
State/Province
Texas
ZIP/Postal Code
78666
Country
United States
Facility Name
Novartis Investigative Site
City
Sherman
State/Province
Texas
ZIP/Postal Code
75092
Country
United States
Facility Name
Novartis Investigative Site
City
Tomball
State/Province
Texas
ZIP/Postal Code
77375
Country
United States
Facility Name
Novartis Investigative Site
City
Midlothian
State/Province
Virginia
ZIP/Postal Code
23114
Country
United States
Facility Name
Novartis Investigative Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32978755
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.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=471
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

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

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