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

NCT ID: NCT02970669

Last Updated: 2021-10-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-16

Study Completion Date

2018-03-19

Brief Summary

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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.

Detailed Description

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Conditions

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Heart Failure, Reduced Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

sacubitril/valsartan (LCZ696)

Intervention Type DRUG

sacubitril/valsartan tablet taken orally.

enalapril

Intervention Type DRUG

Enalapril tablet taken orally.

matching placebo sacubitril/valsartan (LCZ696)

Intervention Type DRUG

matching placebo sacubitril/valsartan tablet taken orally

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.

Group Type EXPERIMENTAL

sacubitril/valsartan (LCZ696)

Intervention Type DRUG

sacubitril/valsartan tablet taken orally.

matching placebo enalapril

Intervention Type DRUG

matching placebo enalapril tablet taken orally

Interventions

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sacubitril/valsartan (LCZ696)

sacubitril/valsartan tablet taken orally.

Intervention Type DRUG

enalapril

Enalapril tablet taken orally.

Intervention Type DRUG

matching placebo sacubitril/valsartan (LCZ696)

matching placebo sacubitril/valsartan tablet taken orally

Intervention Type DRUG

matching placebo enalapril

matching placebo enalapril tablet taken orally

Intervention Type DRUG

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Fort Payne, Alabama, United States

Site Status

Novartis Investigative Site

Beverly Hills, California, United States

Site Status

Novartis Investigative Site

Stockton, California, United States

Site Status

Novartis Investigative Site

West Hills, California, United States

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Novartis Investigative Site

Doral, Florida, United States

Site Status

Novartis Investigative Site

Inverness, Florida, United States

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Novartis Investigative Site

Ormond Beach, Florida, United States

Site Status

Novartis Investigative Site

Port Orange, Florida, United States

Site Status

Novartis Investigative Site

Lutherville, Maryland, United States

Site Status

Novartis Investigative Site

East Brunswick, New Jersey, United States

Site Status

Novartis Investigative Site

Ridgewood, New Jersey, United States

Site Status

Novartis Investigative Site

Columbia, South Carolina, United States

Site Status

Novartis Investigative Site

Greenville, South Carolina, United States

Site Status

Novartis Investigative Site

Lancaster, South Carolina, United States

Site Status

Novartis Investigative Site

Allen, Texas, United States

Site Status

Novartis Investigative Site

McKinney, Texas, United States

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Novartis Investigative Site

New Braunfels, Texas, United States

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Novartis Investigative Site

San Antonio, Texas, United States

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Novartis Investigative Site

San Marcos, Texas, United States

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Novartis Investigative Site

Sherman, Texas, United States

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Novartis Investigative Site

Tomball, Texas, United States

Site Status

Novartis Investigative Site

Midlothian, Virginia, United States

Site Status

Novartis Investigative Site

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 32978755 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=471

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

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CLCZ696BUS14

Identifier Type: -

Identifier Source: org_study_id

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