Barostim Neo® - Baroreflex Activation Therapy® for Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- CVRx, Inc.
- 入组人数
- 1,090
- 试验地点
- 92
- 主要终点
- Major Adverse Neurological and Cardiovascular Events (MANCE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 >
- •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.
研究组 & 干预措施
Device and 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.
干预措施: BAROSTIM NEO® System (Device)
Device and 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.
干预措施: Medical Management (Drug)
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.
干预措施: Medical Management (Drug)
结局指标
主要结局
Major Adverse Neurological and Cardiovascular Events (MANCE)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
未报告次要终点