ANTHEM-HFrEF Pivotal Study

NCT ID: NCT03425422

Last Updated: 2023-10-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

533 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-01

Study Completion Date

2023-05-31

Brief Summary

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A multi-center randomized controlled clinical trial to evaluate Autonomic Regulation Therapy with the VITARIA system in patients with symptomatic heart failure and reduced ejection fraction.

Detailed Description

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ANTHEM-HFrEF is a multi-center, open-label, randomized controlled clinical trial with an adaptive design. Patients with symptomatic heart failure and reduced LVEF will be enrolled and randomized 2:1 to receive VITARIA system implantation on the right cervical vagus nerve in addition to stable guideline-directed medical therapy (therapy), or to continue receiving stable guideline-directed medical therapy alone (control arm).

Subjects in the therapy arm will receive continuous, periodic VNS stimulation after surgery is completed, and will undergo visits for VNS up titration over a period of 3 months. Subjects in the control arm will also undergo scheduled visits at a similar frequency as the titration visits that are scheduled for subjects in the therapy arm. Data for safety and efficacy assessments will be collected for both study arms at 4 weeks post-randomization, every 3 months for the first 12 months, and every 4 months thereafter.

Conditions

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Heart Failure Heart Failure, Congestive Heart Failure, Systolic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Therapy

VITARIA system implantation on the right cervical vagus nerve in addition to stable guideline-directed medical therapy

Group Type EXPERIMENTAL

VITARIA System

Intervention Type DEVICE

Chronic stimulation of the right cervical vagus nerve

Control

Stable guideline-directed medical therapy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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VITARIA System

Chronic stimulation of the right cervical vagus nerve

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Age 18 or above
2. Willing and capable of providing informed consent
3. Capable of participating in all testing associated with this clinical investigation
4. Stable, guideline-directed medical therapy for at least 4 weeks before subject screening. Unrestricted changes in diuretics are allowed during the 4 weeks, as long as the subject remains on a diuretic. If the use of an ARNI is being contemplated for a study subject, ARNI should be administered, and GDMT optimized, before the subject is randomized. No more than a 100% increase or 50% decrease of the dosage of any medication other than a diuretic is permitted. For these medications, medication changes within a class are allowed, as long as the equivalent dosage is within these specified limits
5. Stable symptomatic heart failure NYHA class III; or NYHA class II with a heart failure hospitalization in the previous 12 months. HF hospitalization may include an overnight hospital or hospital-based observation unit stay with a primary diagnosis of HF, or an emergency department visit with a primary diagnosis of HF, and will in either case include documentation of intravenous HF therapy administration or other intervention for HF
6. Left ventricular ejection fraction (EF) ≤ 35% and left ventricular end-diastolic diameter (LVEDD) \< 8.0 cm, as confirmed by the core echocardiography laboratory during screening
7. N-terminal pro-BNP (NT-proBNP) level of at least 800 pg/mL, as determined by the core laboratory; or NT-proBNP level of at least 1200 pg/mL, as determined by the core laboratory, for patients with permanent atrial fibrillation or reporting signs or symptoms of atrial fibrillation at the time that the NT-proBNP sample is drawn
8. Received a standard cardiac assessment, including history, physical exam, and electrocardiogram, and determined by a heart failure cardiologist and study surgeon to be an appropriate candidate for the study's surgical procedure
9. Physically capable and willing to perform repeated 6-minute walk tests associated with the study, and having a baseline distance of between 150 and 450 meters. Symptoms limiting the duration of the 6 minute walk test must be due primarily to heart failure

Exclusion Criteria

1. Refractory symptomatic hypotension (systolic blood pressure below 80 mmHg)
2. Complete AV block treated with unipolar pacemaker therapy
3. Currently implanted vagus nerve stimulation (VNS) device, baroreceptor activation therapy (BAT) device, other nerve stimulator, artificial or donor heart, or ventricular assist device (VAD)
4. Heart failure of non-ischemic origin for less than 6 months, or due to congenital heart disease, hypertrophic obstructive cardiomyopathy, or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis)
5. Moderate (3+) or severe (4+) aortic valve or mitral valve stenosis; moderate (3+) or severe (4+) aortic valve insufficiency; or severe (4+) mitral valve insufficiency
6. Symptomatic uncontrolled bradycardia
7. On renal dialysis
8. Involvement in any concurrent clinical study with an investigational therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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LivaNova

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

Central Arkansas Veterans Healthcare System

Little Rock, Arkansas, United States

Site Status

Long Beach Memorial Hospital

Long Beach, California, United States

Site Status

Greater Los Angeles VA Medical Center

Los Angeles, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

First Coast Cardiovascular Institute

Jacksonville, Florida, United States

Site Status

UnityPoint Health - Methodist Hospital

Peoria, Illinois, United States

Site Status

Indiana University Health Ball Memorial Hospital

Muncie, Indiana, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Lahey Medical Center

Burlington, Massachusetts, United States

Site Status

Michigan Heart, PC

Ypsilanti, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Mount Sinai School St. Luke's

New York, New York, United States

Site Status

MetroHealth System

Cleveland, Ohio, United States

Site Status

ProMedica Northwest Ohio Cardiology Consultants

Toledo, Ohio, United States

Site Status

Penn State Health Milton Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Pinnacle Health

Wormleysburg, Pennsylvania, United States

Site Status

Baylor St. Luke's Medical Center

Houston, Texas, United States

Site Status

Tyler Cardiovascular Consultants

Tyler, Texas, United States

Site Status

Providence Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS. Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Card Fail. 2014 Nov;20(11):808-16. doi: 10.1016/j.cardfail.2014.08.009. Epub 2014 Sep 1.

Reference Type BACKGROUND
PMID: 25187002 (View on PubMed)

Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS. Extended Follow-Up of Patients With Heart Failure Receiving Autonomic Regulation Therapy in the ANTHEM-HF Study. J Card Fail. 2016 Aug;22(8):639-42. doi: 10.1016/j.cardfail.2015.11.002. Epub 2015 Nov 11.

Reference Type BACKGROUND
PMID: 26576716 (View on PubMed)

Konstam MA, Udelson JE, Butler J, Klein HU, Parker JD, Teerlink JR, Wedge PM, Saville BR, Ardell JL, Libbus I, DiCarlo LA. Impact of Autonomic Regulation Therapy in Patients with Heart Failure: ANTHEM-HFrEF Pivotal Study Design. Circ Heart Fail. 2019 Nov;12(11):e005879. doi: 10.1161/CIRCHEARTFAILURE.119.005879. Epub 2019 Nov 14.

Reference Type DERIVED
PMID: 31722536 (View on PubMed)

Related Links

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http://www.artforheartfailure.com

ANTHEM-HFrEF Study Site

Other Identifiers

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C-07

Identifier Type: -

Identifier Source: org_study_id

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