Clinical trial NCT02627196: Baroreflex Activation Therapy for Heart Failure
Official title: Barostim Neo® - Baroreflex Activation Therapy® for Heart Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure
Lead sponsor: CVRx, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-10
Enrollment: 1200
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age 21 years or above.
2. 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).
3. Left ventricular ejection fraction ≤ 35% within 45 days prior to randomization.
4. 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.
5. 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.
6. Six-minute hall walk (6MHW) ≥ 150 m AND ≤ 400 m within 45 days prior to randomization.
7. 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:

     1. Below the level of the mandible AND
     2. No ulcerative carotid arterial plaques AND
     3. No carotid atherosclerosis producing a 50% or greater reduction in linear diameter in the internal carotid AND
     4. 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.
8. 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.
9. 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.
10. 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.
11. Signed a CVRx-approved informed consent form for participation in this trial.

Exclusion Criteria:

If any of the following criteria are met, subjects are not eligible for this trial.

1. Received cardiac resynchronization therapy (CRT) within six months of randomization, or is actively receiving CRT.
2. 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. ,
3. Known or suspected baroreflex failure or autonomic neuropathy.
4. AHA/ACC Stage D heart failure within 45 days prior to randomization.
5. Body mass index \> 40.
6. Serum estimated glomerular filtration rate (eGFR) \< 25 mL/min/1.73 m2 within 45 days prior to randomization.
7. 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.)
8. Recurring symptomatic hypotension within 45 days prior to randomization.
9. Significant uncontrolled symptomatic bradyarrhythmias or unstable ventricular arrhythmias.
10. 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.
11. Episode of NYHA class IV heart failure with acute pulmonary edema within 45 days prior to randomization.
12. 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
13. Solid organ or hematologic transplant, or currently being actively evaluated for an organ transplant.
14. Has received or is receiving LVAD therapy.
15. Has received or is receiving chronic dialysis.
16. Heart failure secondary to a reversible cause, such as cardiac structural valvular disease, acute myocarditis and pericardial constriction.
17. Primary pulmonary hypertension.
18. Infiltrative cardiomyopathy (e.g. cardiac amyloidosis).
19. Severe COPD or severe restrictive lung disease (e.g. requires chronic steroid use or home oxygen use).
20. Active malignancy.
21. Current or planned treatment with intravenous positive inotrope therapy.
22. Life expectancy less than one year.
23. Clinically significant psychological condition that in the physician's opinion would prohibit the subject's ability to meet the protocol requirements.
24. Unable or unwilling to fulfill the protocol medication compliance, testing, and follow-up requirements (e.g. recent drug abuse).
25. Enrolled and active in another (e.g. device, pharmaceutical, or biological) clinical trial unless approved by the CVRx Clinical department.
26. Subjects with known allergies to silicone and titanium.

Primary outcomes:
measure: Rate of Cardiovascular Mortality and Heart Failure Morbidity
timeFrame: At study completion, approximately 5 years
measure: Major Adverse Neurological and Cardiovascular Events (MANCE)
timeFrame: 6 months post implant
measure: Amino-terminal prohormone of brain natriuretic peptide (NT-proBNP)
timeFrame: 6 months post implant
measure: Six Minute Hall Walk (6MHW)
timeFrame: 6 months post implant.
measure: Minnesota Living With Heart Failure Quality of Life (MLWHF QOL)
timeFrame: 6 months post implant
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Heart and Rhythm Solutions, PLLC
state: Arizona
city: Mesa
country: United States
facility: Chan Heart Rhythm Institute
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arrhythmia Research Center
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: Phoenix
country: United States
facility: Cardiovascular Consultants, Ltd.
state: Arizona
city: Fayetteville
country: United States
facility: Washington Regional Medical Center
state: Arkansas
city: Bakersfield
country: United States
facility: Central Cardiology Medical Center
state: California
city: Chula Vista
country: United States
facility: Chula Vista Cardiac Center
state: California
city: Chula Vista
country: United States
facility: Sharp Grossmont
state: California
city: Chula Vista
country: United States
facility: Sharp Chula Vista Medical Center
state: California
city: Concord
country: United States
facility: John Muir Health Clinical Research Center
state: California
city: Fresno
country: United States
facility: University of California, San Francisco - Fresno
state: California
city: Fresno
country: United States
facility: Herndon Surgery Center
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Laguna Hills
country: United States
facility: Memorial Health Services
state: California
city: Los Alamitos
country: United States
facility: Los Alamitos Cardiovascular
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Mountain View
country: United States
facility: Advanced Cardiovascular Specialists
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Palm Springs
country: United States
facility: Desert Heart Regional Medical Center
state: California
city: Pasadena
country: United States
facility: Huntington Hospital
state: California
city: Sacramento
country: United States
facility: Dignity Health
state: California
city: Saint Helena
country: United States
facility: Adventist Heart Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Bonometti, Inc
state: California
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Loveland
country: United States
facility: Medical Center of the Rockies Research
state: Colorado
city: Atlantis
country: United States
facility: Atlantic Clinical Research Center - Cardiology
state: Florida
city: Clearwater
country: United States
facility: Clearwater Cardiovascular Consultants
state: Florida
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Cardiovascular Institute
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Pensacola
country: United States
facility: Avanza Medical Research Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Macon
country: United States
facility: Mercer University
state: Georgia
city: Marietta
country: United States
facility: WellStar Medical Group
state: Georgia
city: Boise
country: United States
facility: St. Alphonsus Medical Center
state: Idaho
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Naperville
country: United States
facility: Advocate Medical Group
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Wichita
country: United States
facility: Via Christi Research
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University & Vascular Institute
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Brighton
country: United States
facility: St. Elizabeth's Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Detroit Medical Center Cardiovascular Institute
state: Michigan
city: Saginaw
country: United States
facility: Ascension St. Mary's Research Institute
state: Michigan
city: Southfield
country: United States
facility: Providence-Providence Park Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Heart and Vascular
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Healthcare Partners Clinical Research
state: Nevada
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Presbyterian Heart Group
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital - Long Island
state: New York
city: Greensboro
country: United States
facility: Cone Health
state: North Carolina
city: Raleigh
country: United States
facility: WakeMed
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular Research Group
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny-Singer Research Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Florence
country: United States
facility: McLeod Cardiology Associates
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular Foundation
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research Foundation
state: Texas
city: Dallas
country: United States
facility: Cardiovascular Research Institute of Dallas
state: Texas
city: Houston
country: United States
facility: Private Practice Leadership
state: Texas
city: Richardson
country: United States
facility: Methodist Richardson Medical Center
state: Texas
city: Tyler
country: United States
facility: Tyler Cardiovascular Consultants
state: Texas
city: Murray
country: United States
facility: Intermountain Heart Institute
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Tacoma
country: United States
facility: CHI Franciscan Health Research Center
state: Washington
city: Milwaukee
country: United States
facility: Columbia St. Mary's Hospital
state: Wisconsin
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
state: Cambridgeshire
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
state: Merseyside
city: Harefield
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
state: Middlesex
city: Belfast
country: United Kingdom
facility: Belfast Health & Social Care Trust
state: Northern Ireland
Study officials:
affiliation: Medical University of South Carolina
name: Michael Zile, MD
role: STUDY_CHAIR
affiliation: Ohio State University
name: William Abraham, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Fred Weaver, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm Centre d'Investigation, CHU de Nancy
name: Faiez Zannad, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt Heart and Vascular Institute
name: JoAnn Lindenfield, MD
role: PRINCIPAL_INVESTIGATOR
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