Baroreflex Activation Therapy for Heart Failure
- Conditions
- Heart Failure
- Interventions
- Drug: Medical ManagementDevice: BAROSTIM NEO® System
- Registration Number
- NCT02627196
- Lead Sponsor
- CVRx, Inc.
- Brief Summary
The purpose of this clinical trial (NCT02627196) is to develop valid scientific evidence for safety and effectiveness of Baroreflex Activation Therapy with the BAROSTIM NEO System in subjects with heart failure, defined as New York Heart Association (NYHA) functional Class III, left ventricular ejection fraction (LVEF) ≤ 35% and NT-proBNP\<1600 pg/ml despite being treated with the appropriate heart failure guideline directed therapy, excluding subjects eligible for or actively receiving Cardiac Resynchronization Therapy (CRT).
The total trial duration is anticipated to be approximately 5 years; however, the duration of an individual subject enrollment will depend on when he or she entered the trial.
- Detailed Description
The BAROSTIM NEO - Baroreflex Activation Therapy for Heart Failure is a prospective, randomized trial in subjects with reduced ejection fraction heart failure. Subjects will be randomized in a 1:1 ratio to receive Barostim Activation Therapy with an implanted BAROSTIM NEO System in addition to medical management or to receive medical management alone (no device implant). The trial will be conducted at up to 120 investigational centers in the U.S. and up to 20 investigational centers outside the U.S. These centers will enroll up to 1200 subjects to randomize approximately 480 subjects who meet the entry criteria.
For all subjects, trial visits will occur at 0.5, 1, 1.5, 2, 3, 6, 9 and 12 months post-implant (post anticipated implant for medical management). Visits will occur quarterly from 15 to 24 months and semi-annually thereafter.
Subjects are followed in an identical manner regardless of trial arm.
The data will provide evidence of the safety and efficacy of BAROSTIM THERAPY. The accumulated morbidity and mortality data collected will provide evidence of morbidity and mortality benefit. This trial will involve one or more interim analyses to evaluate when sufficient evidence is reached for the final morbidity and mortality analysis.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1200
-
Age 21 years or above.
-
Currently NYHA Class II or III heart failure. For NYHA Class II, must have been NYHA Class III at any point in time within 3 calendar months prior to enrollment or at time of screening (enrollment is defined as the date the subject provided written consent).
-
Left ventricular ejection fraction ≤ 35% within 45 days prior to randomization.
-
Heart failure accompanied by either:
- Core lab NT-proBNP ≥ 400 AND <1600 pg/ml within 45 days prior to randomization OR
- Core lab NT-proBNP < 400 pg/ml within 45 days prior to randomization AND a heart failure hospitalization in the past 12 months.
Note: Heart failure hospitalization may include an overnight hospital or hospital-based observation unit stay with a primary diagnosis of heart failure or an emergency room visit with a primary diagnosis of heart failure.
Note: Screening/Baseline core lab NT-proBNP must be collected in an outpatient setting at a time when the subject is thought to be clinically stable.
-
On optimal, stable, Guideline Directed Medical Therapy (GDMT) per country specific guidelines for the treatment of heart-failure throughout screening/baseline evaluation and for at least 4 weeks prior to obtaining any post-consent screening parameters:
- No more than a 100% increase or a 50% decrease of the dosage of any one medication other than a diuretic.
- Medication changes within a drug class are allowed as long as the equivalent dosage is within the limits specified above.
- Unrestricted changes in diuretics are allowed as long as the subject remains on a diuretic.
-
Six-minute hall walk (6MHW) ≥ 150 m AND ≤ 400 m within 45 days prior to randomization.
-
The artery planned for the BAROSTIM implant must meet both of the following criteria:
-
At least one carotid bifurcation as identification by a bilateral carotid duplex ultrasound within 6 months prior to randomization that is:
- Below the level of the mandible AND
- No ulcerative carotid arterial plaques AND
- No carotid atherosclerosis producing a 50% or greater reduction in linear diameter in the internal carotid AND
- No carotid atherosclerosis producing a 50% or greater reduction in linear diameter in the distal common carotid
-
No prior surgery, radiation, or endovascular stent placement in the carotid artery or the carotid sinus region.
-
-
If female and of childbearing potential, must use a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) and agree to continue use of this method for the duration of the trial. Women of childbearing potential must have a negative pregnancy test within 14 days prior to randomization.
-
Received a standard cardiac work up and is an appropriate candidate for the study and the surgical procedure as determined by a trial cardiologist and a trial surgeon.
-
Subjects implanted with a cardiac rhythm management device that does not utilize an intracardiac lead, or implanted with a neurostimulation device, must be approved by the CVRx Clinical department.
-
Signed a CVRx-approved informed consent form for participation in this trial.
If any of the following criteria are met, subjects are not eligible for this trial.
-
Received cardiac resynchronization therapy (CRT) within six months of randomization, or is actively receiving CRT.
-
Currently have a Class I indication for a cardiac resynchronization therapy (CRT) device according to AHA/ACC/ESC guidelines for the treatment of congestive heart failure. ,
-
Known or suspected baroreflex failure or autonomic neuropathy.
-
AHA/ACC Stage D heart failure within 45 days prior to randomization.
-
Body mass index > 40.
-
Serum estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73 m2 within 45 days prior to randomization.
-
Recurring resting heart rate of either < 60 bpm or > 100 bpm via clinic measurements within 45 days prior to randomization. (Note: Heart rate <60 bpm is not applicable to subjects with an implanted device capable of pacing.)
-
Recurring symptomatic hypotension within 45 days prior to randomization.
-
Significant uncontrolled symptomatic bradyarrhythmias or unstable ventricular arrhythmias.
-
Subjects with any surgery that has occurred, or is planned to occur, within 45 days of the BAROSTIM NEO implant procedure. This includes pacemaker or ICD implants or battery replacements.
-
Episode of NYHA class IV heart failure with acute pulmonary edema within 45 days prior to randomization.
-
Any of the following within 3 months of randomization:
- Myocardial infarction
- Unstable angina
- Percutaneous coronary intervention (e.g. CABG or PTCA)
- Cerebral vascular accident or transient ischemic attack
- Sudden cardiac death
-
Solid organ or hematologic transplant, or currently being actively evaluated for an organ transplant.
-
Has received or is receiving LVAD therapy.
-
Has received or is receiving chronic dialysis.
-
Heart failure secondary to a reversible cause, such as cardiac structural valvular disease, acute myocarditis and pericardial constriction.
-
Primary pulmonary hypertension.
-
Infiltrative cardiomyopathy (e.g. cardiac amyloidosis).
-
Severe COPD or severe restrictive lung disease (e.g. requires chronic steroid use or home oxygen use).
-
Active malignancy.
-
Current or planned treatment with intravenous positive inotrope therapy.
-
Life expectancy less than one year.
-
Clinically significant psychological condition that in the physician's opinion would prohibit the subject's ability to meet the protocol requirements.
-
Unable or unwilling to fulfill the protocol medication compliance, testing, and follow-up requirements (e.g. recent drug abuse).
-
Enrolled and active in another (e.g. device, pharmaceutical, or biological) clinical trial unless approved by the CVRx Clinical department.
-
Subjects with known allergies to silicone and titanium.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Medical Management Medical Management Subjects will receive optimal, stable, Guideline Directed Medical Therapy (GDMT) for heart failure (American Heart Association \[AHA\] / American College of Cardiology \[ACC\] guidelines), including drugs to be determined by the subject's physician. Drug types include: Loop Diuretics, Thiazide Diuretics, Potassium-sparing Diuretics, Sequential Nephron Blockade, ACE Inhibitors, ARBs, ARNI, Aldosterone Antagonists, Beta Blockers and Hydralazine and Isosorbide Dinitrate. Device and Medical Management BAROSTIM NEO® System Subjects will be implanted with the BAROSTIM NEO System and receive optimal, stable, Guideline Directed Medical Therapy (GDMT) for heart failure (American Heart Association \[AHA\] / American College of Cardiology \[ACC\] guidelines), including drugs to be determined by the subject's physician. Drug types include: Loop Diuretics, Thiazide Diuretics, Potassium-sparing Diuretics, Sequential Nephron Blockade, ACE Inhibitors, ARBs, ARNI, Aldosterone Antagonists, Beta Blockers and Hydralazine and Isosorbide Dinitrate. Device and Medical Management Medical Management Subjects will be implanted with the BAROSTIM NEO System and receive optimal, stable, Guideline Directed Medical Therapy (GDMT) for heart failure (American Heart Association \[AHA\] / American College of Cardiology \[ACC\] guidelines), including drugs to be determined by the subject's physician. Drug types include: Loop Diuretics, Thiazide Diuretics, Potassium-sparing Diuretics, Sequential Nephron Blockade, ACE Inhibitors, ARBs, ARNI, Aldosterone Antagonists, Beta Blockers and Hydralazine and Isosorbide Dinitrate.
- Primary Outcome Measures
Name Time Method Major Adverse Neurological and Cardiovascular Events (MANCE) 6 months post implant To demonstrate the safety of the Barostim NEO® System via the event-free rate of all system- and procedure-related Major Adverse Neurological and Cardiovascular Events (MANCE) occurring within 6 months post implant in the device arm.
Minnesota Living With Heart Failure Quality of Life (MLWHF QOL) 6 months post implant To demonstrate that treatment with the BAROSTIM NEO® System results in a larger improvement in MLWHF QOL at 6 months than medical management
Six Minute Hall Walk (6MHW) 6 months post implant. To demonstrate that treatment with the BAROSTIM NEO® system results in a larger improvement in 6MHW at 6 months than medical management
Rate of Cardiovascular Mortality and Heart Failure Morbidity At study completion, approximately 5 years To demonstrate that treatment with the BAROSTIM NEO® System, relative to medical management, reduces the rate of cardiovascular mortality or worsening heart failure that leads to hospitalization, cardiac assist device or heart transplant.
Amino-terminal prohormone of brain natriuretic peptide (NT-proBNP) 6 months post implant To demonstrate that treatment with the BAROSTIM NEO® system results in a larger reduction in NT-proBNP at 6 months than medical management.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (92)
Memorial Health Services
🇺🇸Laguna Hills, California, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
NorthShore University Health System
🇺🇸Evanston, Illinois, United States
UC Irvine Health
🇺🇸Orange, California, United States
Huntington Hospital
🇺🇸Pasadena, California, United States
Avanza Medical Research Center
🇺🇸Pensacola, Florida, United States
Bonometti, Inc
🇺🇸Santa Barbara, California, United States
Memorial Cardiovascular Institute
🇺🇸Hollywood, Florida, United States
Southern California Permanente Medical Group
🇺🇸Los Angeles, California, United States
Adventist Heart Institute
🇺🇸Saint Helena, California, United States
St. Louis Heart and Vascular
🇺🇸Saint Louis, Missouri, United States
Nebraska Heart Institute
🇺🇸Lincoln, Nebraska, United States
Advanced Cardiovascular Specialists
🇺🇸Mountain View, California, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
St. Alphonsus Medical Center
🇺🇸Boise, Idaho, United States
Sharp Grossmont
🇺🇸Chula Vista, California, United States
Los Alamitos Cardiovascular
🇺🇸Los Alamitos, California, United States
Medical Center of the Rockies Research
🇺🇸Loveland, Colorado, United States
Mercer University
🇺🇸Macon, Georgia, United States
WellStar Medical Group
🇺🇸Marietta, Georgia, United States
Advocate Medical Group
🇺🇸Naperville, Illinois, United States
Ascension St. Mary's Research Institute
🇺🇸Saginaw, Michigan, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Deborah Heart and Lung Center
🇺🇸Browns Mills, New Jersey, United States
Cardiovascular Institute of the South
🇺🇸Houma, Louisiana, United States
Mercy Hospital St. Louis
🇺🇸Saint Louis, Missouri, United States
Cone Health
🇺🇸Greensboro, North Carolina, United States
St. Francis Hospital - Long Island
🇺🇸Roslyn, New York, United States
McLeod Cardiology Associates
🇺🇸Florence, South Carolina, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Methodist Richardson Medical Center
🇺🇸Richardson, Texas, United States
Stern Cardiovascular Foundation
🇺🇸Germantown, Tennessee, United States
Private Practice Leadership
🇺🇸Houston, Texas, United States
Healthcare Partners Clinical Research
🇺🇸Las Vegas, Nevada, United States
Via Christi Research
🇺🇸Wichita, Kansas, United States
Arizona Arrhythmia Research Center
🇺🇸Phoenix, Arizona, United States
Phoenix Cardiovascular Research Group
🇺🇸Phoenix, Arizona, United States
Cardiovascular Consultants, Ltd.
🇺🇸Phoenix, Arizona, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Heart and Rhythm Solutions, PLLC
🇺🇸Chandler, Arizona, United States
Chan Heart Rhythm Institute
🇺🇸Mesa, Arizona, United States
Washington Regional Medical Center
🇺🇸Fayetteville, Arkansas, United States
Central Cardiology Medical Center
🇺🇸Bakersfield, California, United States
Chula Vista Cardiac Center
🇺🇸Chula Vista, California, United States
Sharp Chula Vista Medical Center
🇺🇸Chula Vista, California, United States
Glendale Adventist Medical Center
🇺🇸Glendale, California, United States
University of California, San Francisco - Fresno
🇺🇸Fresno, California, United States
Herndon Surgery Center
🇺🇸Fresno, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Clearwater Cardiovascular Consultants
🇺🇸Clearwater, Florida, United States
Atlantic Clinical Research Center - Cardiology
🇺🇸Atlantis, Florida, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸Kansas City, Kansas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
St. Elizabeth's Medical Center
🇺🇸Brighton, Massachusetts, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
University of Rochester
🇺🇸Rochester, New York, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
WakeMed
🇺🇸Raleigh, North Carolina, United States
Oklahoma Cardiovascular Research Group
🇺🇸Oklahoma City, Oklahoma, United States
Drexel University
🇺🇸Philadelphia, Pennsylvania, United States
Cardiovascular Research Institute of Dallas
🇺🇸Dallas, Texas, United States
Intermountain Heart Institute
🇺🇸Murray, Utah, United States
Tyler Cardiovascular Consultants
🇺🇸Tyler, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Royal Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Liverpool Heart and Chest Hospital
🇬🇧Liverpool, Merseyside, United Kingdom
Belfast Health & Social Care Trust
🇬🇧Belfast, Northern Ireland, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust
🇬🇧Harefield, Middlesex, United Kingdom
Detroit Medical Center Cardiovascular Institute
🇺🇸Detroit, Michigan, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Columbia St. Mary's Hospital
🇺🇸Milwaukee, Wisconsin, United States
Providence-Providence Park Hospital
🇺🇸Southfield, Michigan, United States
John Muir Health Clinical Research Center
🇺🇸Concord, California, United States
Hoag Memorial Hospital
🇺🇸Newport Beach, California, United States
Allegheny-Singer Research Institute
🇺🇸Pittsburgh, Pennsylvania, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
CHI Franciscan Health Research Center
🇺🇸Tacoma, Washington, United States
Desert Heart Regional Medical Center
🇺🇸Palm Springs, California, United States
Presbyterian Heart Group
🇺🇸Albuquerque, New Mexico, United States
Dignity Health
🇺🇸Sacramento, California, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Texas Cardiac Arrhythmia Research Foundation
🇺🇸Austin, Texas, United States
Tulane University & Vascular Institute
🇺🇸New Orleans, Louisiana, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Prairie Education and Research Cooperative
🇺🇸Springfield, Illinois, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States