ANTHEM-HFrEF Pivotal Study

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03425422
• Other study ID #: C-07
• Status: Terminated
• Phase: N/A
• Start date: May 1, 2018
• Est. completion date: May 31, 2023

Study information

• Verified date: October 2023
• Source: LivaNova
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 533
• Est. completion date: May 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Congestive
• Heart Failure, Systolic

Intervention

Device:
• VITARIA System
Chronic stimulation of the right cervical vagus nerve

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Lahey Medical Center	Burlington	Massachusetts
United States	MetroHealth System	Cleveland	Ohio
United States	Hartford Hospital	Hartford	Connecticut
United States	Penn State Health Milton Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor St. Luke's Medical Center	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	First Coast Cardiovascular Institute	Jacksonville	Florida
United States	Central Arkansas Veterans Healthcare System	Little Rock	Arkansas
United States	Long Beach Memorial Hospital	Long Beach	California
United States	Greater Los Angeles VA Medical Center	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Indiana University Health Ball Memorial Hospital	Muncie	Indiana
United States	Mount Sinai School St. Luke's	New York	New York
United States	UnityPoint Health - Methodist Hospital	Peoria	Illinois
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	ProMedica Northwest Ohio Cardiology Consultants	Toledo	Ohio
United States	University of Arizona	Tucson	Arizona
United States	Tyler Cardiovascular Consultants	Tyler	Texas
United States	Pinnacle Health	Wormleysburg	Pennsylvania
United States	Michigan Heart, PC	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
LivaNova

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free rate	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
Primary	Cardiovascular mortality and HF hospitalization	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

External Links

•   ANTHEM-HFrEF Study Site