Heart Failure
Conditions
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.
Interventions
DEVICEBAROSTIM NEO® System
DRUGMedical Management
Sponsors
CVRx, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Rate of Cardiovascular Mortality and Heart Failure Morbidity | From randomization until data-cut date for the endpoint analysis. Median follow-up was 3.6 years per patient. | 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. Event rates were calculated using negative binomial to account for varying follow-up times. Rates are expressed as events per patient-year, with 95% confidence intervals reflecting dispersion. |
| Percent Change in Log 10 Amino-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) From Baseline to 6 Months Post-implant | 6 months post-implant | To demonstrate that treatment with the BAROSTIM NEO® system results in a larger reduction in NT-proBNP from baseline to 6 months post-implant than medical management. |
| Change to Six Minute Hall Walk (6MHW) | Baseline and 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. The 6 Minute Hall Walk is an assessment of a patient's functional exercise capacity by recording the maximum distance walked in 6 minutes on a flat course in meters (m). A higher score (more distance) indicates better functional capacity. |
| Change in Minnesota Living With Heart Failure Quality of Life (MLWHF QOL) Score | Baseline and 6 months post-implant | To demonstrate that treatment with the BAROSTIM NEO® System results in a larger improvement in MLWHF QOL score at 6 months than medical management. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a validated patient-reported outcome measure assessing the impact of heart failure on quality of life. It includes 21 items rated from 0 to 5 (0 = no impact, 5 = very much impact). The Total Score is the sum of all items and ranges from 0 to 105, with higher scores indicating worse quality of life. |
Countries
United Kingdom, United States
Contacts
STUDY_CHAIRMichael Zile, MD
Medical University of South Carolina
PRINCIPAL_INVESTIGATORWilliam Abraham, MD
Ohio State University
PRINCIPAL_INVESTIGATORFred Weaver, MD
University of Southern California
PRINCIPAL_INVESTIGATORFaiez Zannad, MD
Inserm Centre d'Investigation, CHU de Nancy
PRINCIPAL_INVESTIGATORJoAnn Lindenfield, MD
Vanderbilt Heart and Vascular Institute
Participant flow
Pre-assignment details
The protocol indicates a subject is considered enrolled upon signing the informed consent form. A total of 1090 subjects provided informed consent and were enrolled. Following completion of screening procedures and application of eligibility criteria per protocol, 467 subjects met randomization criteria and were assigned to study arms. The remaining enrolled subjects were considered screen failures and did not proceed to randomization.
Baseline characteristics
| Characteristic | — |
|---|---|
| 6 Minute Hall Walk | 300 meters STANDARD_DEVIATION 71 |
| Age, Continuous | 63 years STANDARD_DEVIATION 10 |
| Left Ventricular Ejection Fraction | 27 % STANDARD_DEVIATION 6 |
| Minnesota Living with Heart Failure Questionnaire | 53 score STANDARD_DEVIATION 24 |
| New York Heart Association Class Class II | 9 participants |
| New York Heart Association Class Class III | 151 participants |
| NT-proBNP | 736 pg/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) White | 120 Participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 162 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 33 / 159 | 42 / 160 |
| other Total, other adverse events | 134 / 163 | 128 / 160 |
| serious Total, serious adverse events | 121 / 163 | 121 / 160 |
Outcome results
None listed