ANTHEM-HFrEF Pivotal Study

October 6, 2023 updated by: LivaNova

Autonomic Regulation Therapy to Enhance Myocardial Function and Reduce Progression of Heart Failure With Reduced Ejection Fraction

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

533

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Central Arkansas Veterans Healthcare System
    • California
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Hospital
      • Los Angeles, California, United States, 90073
        • Greater Los Angeles VA Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
    • Florida
      • Jacksonville, Florida, United States, 32256
        • First Coast Cardiovascular Institute
    • Illinois
      • Peoria, Illinois, United States, 61606
        • UnityPoint Health - Methodist Hospital
    • Indiana
      • Muncie, Indiana, United States, 47303
        • Indiana University Health Ball Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Burlington, Massachusetts, United States, 01805
        • Lahey Medical Center
    • Michigan
      • Ypsilanti, Michigan, United States, 48197
        • Michigan Heart, PC
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • New York
      • New York, New York, United States, 10025
        • Mount Sinai School St. Luke's
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth System
      • Toledo, Ohio, United States, 43606
        • ProMedica Northwest Ohio Cardiology Consultants
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Health Milton Hershey Medical Center
      • Wormleysburg, Pennsylvania, United States, 17043
        • Pinnacle Health
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor St. Luke's Medical Center
      • Tyler, Texas, United States, 75701
        • Tyler Cardiovascular Consultants
    • Washington
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Therapy
VITARIA system implantation on the right cervical vagus nerve in addition to stable guideline-directed medical therapy
Device: VITARIA System
Chronic stimulation of the right cervical vagus nerve
No Intervention: Control
Stable guideline-directed medical therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free rate
Time Frame: 90 days
The event-free rate, through 90 days after VITARIA implantation, from all VITARIA system-related and VITARIA implantation-related serious adverse events, as adjudicated by the Clinical Events Committee
90 days
Cardiovascular mortality and HF hospitalization
Time Frame: Through study completion, an average of 2 years
A composite of cardiovascular mortality or heart failure hospitalization, as adjudicated by the Clinical Events Committee, based on time to first event after randomization
Through study completion, an average of 2 years

Collaborators and Investigators

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

Sponsor

LivaNova

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)

May 1, 2018

Primary Completion (Actual)

May 31, 2023

Study Completion (Actual)

May 31, 2023

Study Registration Dates

First Submitted

January 26, 2018

First Submitted That Met QC Criteria

February 6, 2018

First Posted (Actual)

February 7, 2018

Study Record Updates

Last Update Posted (Estimated)

October 10, 2023

Last Update Submitted That Met QC Criteria

October 6, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C-07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

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.

Clinical Trials on Heart Failure

Clinical Trials on VITARIA System

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Argentina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe