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

NCT02970669 | Completed Phase 4 Results

• 1 other identifier: CLCZ696BUS14
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 23

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, week 8

Secondary Outcomes (5)

• Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 1

  Baseline, Week 1

• Change in Mean Activity Counts During Most Active 30 Minutes of Day From Baseline to Week 9 and 16

  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

  Baseline, Week 8

• Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 1

  Baseline, Week 1

• Change in Mean Activity (Counts Per Minute) During Sleep From Baseline to Week 9 and 16

  Baseline (Sacubitril/Valsartan: week -1 / Enalapril: week 8), week 9 and 16

Study Arms (2)

Enalapril

ACTIVE COMPARATOR

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); Drug: enalapril; Drug: matching placebo sacubitril/valsartan (LCZ696)

Sacubitril/Valsartan

EXPERIMENTAL

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); Drug: matching placebo enalapril

Interventions

sacubitril/valsartan (LCZ696) DRUG

sacubitril/valsartan tablet taken orally.

Enalapril; Sacubitril/Valsartan

enalapril DRUG

Enalapril tablet taken orally.

Enalapril

matching placebo sacubitril/valsartan (LCZ696) DRUG

matching placebo sacubitril/valsartan tablet taken orally

Enalapril

matching placebo enalapril DRUG

matching placebo enalapril tablet taken orally

Sacubitril/Valsartan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Novartis Investigative Site

Fort Payne, Alabama, 35967, United States

Location

Novartis Investigative Site

Beverly Hills, California, 90211, United States

Location

Novartis Investigative Site

Stockton, California, 95204, United States

Location

Novartis Investigative Site

West Hills, California, 91307, United States

Location

Novartis Investigative Site

Doral, Florida, 33126, United States

Location

Novartis Investigative Site

Inverness, Florida, 34452, United States

Location

Novartis Investigative Site

Ormond Beach, Florida, 32174, United States

Location

Novartis Investigative Site

Port Orange, Florida, 32127, United States

Location

Novartis Investigative Site

Lutherville, Maryland, 21093, United States

Location

Novartis Investigative Site

East Brunswick, New Jersey, 08816, United States

Location

Novartis Investigative Site

Ridgewood, New Jersey, 07450, United States

Location

Novartis Investigative Site

Columbia, South Carolina, 29203, United States

Location

Novartis Investigative Site

Greenville, South Carolina, 29615, United States

Location

Novartis Investigative Site

Lancaster, South Carolina, 29720, United States

Location

Novartis Investigative Site

Allen, Texas, 75002-3688, United States

Location

Novartis Investigative Site

McKinney, Texas, 75013, United States

Location

Novartis Investigative Site

New Braunfels, Texas, 78130, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

San Marcos, Texas, 78666, United States

Location

Novartis Investigative Site

Sherman, Texas, 75092, United States

Location

Novartis Investigative Site

Tomball, Texas, 77375, United States

Location

Novartis Investigative Site

Midlothian, Virginia, 23114, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• 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.

  PMID: 32978755 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Heart Failure, Systolic; Dilatation, Pathologic; Hypertrophy, Left Ventricular; Heart Failure; Motor Activity

Interventions

sacubitril; Valsartan; sacubitril and valsartan sodium hydrate drug combination; Enalapril

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Cardiomegaly; Hypertrophy; Behavior

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dipeptides; Oligopeptides; Peptides

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 22, 2016
• Study Start: December 16, 2016
• Primary Completion: March 19, 2018
• Study Completion: March 19, 2018
• Last Updated: October 7, 2021
• Results First Posted: April 8, 2019

Record last verified: 2021-10

Locations

US (23)