ANTHEM-HFrEF Pivotal Study
- Conditions
- Heart FailureHeart Failure, CongestiveHeart Failure, Systolic
- Registration Number
- NCT03425422
- Lead Sponsor
- LivaNova
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 533
- Age 18 or above
- Willing and capable of providing informed consent
- Capable of participating in all testing associated with this clinical investigation
- 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
- 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
- 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
- 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
- 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
- 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
- Refractory symptomatic hypotension (systolic blood pressure below 80 mmHg)
- Complete AV block treated with unipolar pacemaker therapy
- Currently implanted vagus nerve stimulation (VNS) device, baroreceptor activation therapy (BAT) device, other nerve stimulator, artificial or donor heart, or ventricular assist device (VAD)
- 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)
- 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
- Symptomatic uncontrolled bradycardia
- On renal dialysis
- Involvement in any concurrent clinical study with an investigational therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Event-free rate 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
Cardiovascular mortality and HF hospitalization 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (22)
University of Alabama
🇺🇸Birmingham, Alabama, United States
University of Arizona
🇺🇸Tucson, Arizona, 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
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
First Coast Cardiovascular Institute
🇺🇸Jacksonville, Florida, United States
UnityPoint Health - Methodist Hospital
🇺🇸Peoria, Illinois, United States
Indiana University Health Ball Memorial Hospital
🇺🇸Muncie, Indiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Scroll for more (12 remaining)University of Alabama🇺🇸Birmingham, Alabama, United States