INcrease Of VAgal TonE in CHF
- Conditions
- Heart FailureLeft Ventricular Dysfunction
- Interventions
- Other: Standard of CareDevice: CardioFit® System
- Registration Number
- NCT01303718
- Lead Sponsor
- BioControl Medical
- Brief Summary
The purpose of the INOVATE-HF study is to demonstrate the long-term safety and efficacy of vagus nerve stimulation with the CardioFit® system for the treatment of subjects with Heart Failure.
- Detailed Description
Prospective, Randomized (3:2 active:control), Open Label, Event-driven Interventional Study. All subjects undergo the following: Baseline, Randomization, (Implantation \& Optimization for subjects randomized to the active therapy), and Follow-up Period, followed by an Extension period, which lasts until the end of the study. The Clinical Events Committee (CEC) and Data Monitoring and Safety Board (DSMB) will conduct scheduled independent reviews of the data at the following time-points in order to ensure that an ongoing acceptable safety profile is being achieved.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 730
- Chronic symptomatic heart failure in New York Heart Association functional class III.
- Age of at least 18 years.
- Subjects should be predominately in sinus rhythm at the time of enrollment.
- On stable optimally uptitrated medical therapy recommended according to current guidelines as standard of care for heart failure therapy.
- LVEF ≤ 40% per site measurement within three months before enrollment.
- The left ventricular end diastolic diameter, per site measurement, should be between 50 and 80 mm.
- The subject is a male or postmenopausal female. Females of childbearing age may be included if an acceptable contraception measure is used.
- Subject must sign an approved informed consent form. Subject agrees to attend all followup evaluations.
- Subjects with CRT devices may be included in the trial provided they have had CRT for at least 12 months.
- Presence of a life threatening condition or disease other than heart failure, that is likely to lead to death within 6 months.
- Acute myocardial infarction (MI), variant angina pectoris, unstable angina or acute coronary syndrome in the previous one month.
- History of stroke or TIA within the previous 3 months or significant neurological damage that would impair the ability to respond to or detect improvement with the vagal nerve stimulation.
- Coronary Artery Bypass Surgery (CABG), valve replacement or repair, aortic surgery or PCI) in the prior 3 months or planned/anticipated within 6 months.
- Heart failure due to acute myocarditis, restrictive cardiomyopathy, constrictive pericarditis or hemodynamically significant aortic valve insufficiency, aortic stenosis, or mitral valve stenosis.
- Severe renal failure (creatinine level > 3 mg/dL (265 micromole/liter).
- Severe hepatic failure (transaminase level four times ULN, or total bilirubin level > 1.8 mmol/dL).
- Uncontrolled Diabetes Mellitus, which in the opinion of the investigator, would compromise the safety of the implant procedure and/or the ability to respond or detect improvement with vagal nerve stimulation.
- Previous right neck surgery, including for cerebrovascular disease (CVD), malignancy, and previous irradiation therapy of the neck, which in the opinion of the implanting surgeon, would preclude safe implantation of the vagal nerve cuff. Subjects with more than 70% right carotid artery stenosis assessed on carotid ultrasound are excluded.
- Current hypotension (systolic blood pressure below 80 mmHg).
- Active peptic ulcer disease or history of upper GI bleeding, or ulcer within 6 months.
- History of lung disease such as severe asthma, COPD (e.g., FEV1<1.5 liter) or continuous oxygen dependence.
- 2nd or 3rd degree AV block or other pacemaker indication that is not treated with a pacemaker.
- Chronic atrial fibrillation or flutter in the previous 3 months, or hospitalization for AF due to clinical manifestations of such in the last 6 months.
- Use of unipolar sensing
- Congenital or acquired long QT syndrome.
- Documented recorded or suspected vaso-vagal syncope or vaso depressor syncope.
- Treatment by investigational drug or device within the past 3 months.
- The subject must not have received inotropic therapy within 2 months or be considered a possible candidate for inotropic therapy within the next 1 month.
- Inability to understand the informed consent and/or prior diagnosis of major affective disorder e.g., major depression or bipolar disorder or schizophrenia that requires ongoing treatment and is not adequately controlled by medication.
- Subjects transplanted with heart or other tissues or organs, or on a heart transplant waiting list and anticipated to receive a transplant within 6 months of randomization.
- Immunosuppressed subjects; subjects under systemic steroid treatment.
- Anemia with Hgb ≤ 9.5 g/L. Treatment with erythropoietin or other similar agents is allowed if used to keep Hgb > 9.5 g/L.
- Untreated obstructive sleep apnea ("OSA") with apnea-hypopnea index of 15 or more; or OSA that is treated for less than 3-months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of Care Standard of Care Usual care (no CardioFit System implant) CardioFit® System CardioFit® System Vagal nerve stimulation with the CardioFit® system
- Primary Outcome Measures
Name Time Method Number of participants reaching all-cause mortality or unplanned heart failure hospitalization or equivalent. Until the end of the study The primary efficacy end-point of the study is the composite of all-cause mortality or unplanned heart failure hospitalization equivalent using a time to first event analysis, as compared between the two study arms after a pre-specified number of such events have been accumulated.
Co-Primary Safety Endpoints: a) Freedom from procedure and system related complication events and b) Number of all-cause death cases or complications resulting in hospitalization a) 90 days and b) Until the end of the study The co-primary safety endpoints of the study are the following:
1. Freedom from procedure and system related complication events through 90 days
2. Demonstrate time to first event equivalence in all-cause mortality and complications resulting in prolonged hospitalization between the Control and CardioFit
- Secondary Outcome Measures
Name Time Method The rate of unplanned heart failure hospitalization equivalents Until the end of the study The rate of unplanned heart failure hospitalization equivalents
Mean improvement in LVESVi from baseline to 12-months 12 Months Mean improvement in LVESVi from baseline to 12-months
Mean improvement in the summary score of the KCCQ from baseline to 12-months 12 Months Mean improvement in the summary score of the KCCQ from baseline to 12-months
Mean improvement in 6 minute walk test from baseline to 12-months 12 Months Mean improvement in 6 minute walk test from baseline to 12-months
All cause mortality and the number of unplanned heart failure hospitalization equivalents Until the end of the study All cause mortality and the number of unplanned heart failure hospitalization equivalents
Rate of hospitalization-free days Until the end of the study Rate of hospitalization-free days
Secondary Safety Endpoints: Mortality and Complications Until the end of the study The following additional (secondary) safety endpoint data will also be evaluated comparatively at 6- and 12-months:
1. All-cause mortality
2. Cardiovascular mortality
3. Serious adverse events
4. Complications
5. System- or procedure-related complications
Trial Locations
- Locations (87)
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Chula Vista Heart Clinic
🇺🇸San Diego, California, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
St Lukes Episcopal
🇺🇸Houston, Texas, United States
Glendale Memorial Hospital
🇺🇸Glendale, California, United States
Saint Vincent Medical Group
🇺🇸Indianapolis, Indiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Community Heart and Vascular Clinic
🇺🇸Indianapolis, Indiana, United States
St. Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Bryan Heart Institute
🇺🇸Lincoln, Nebraska, United States
Health Care Partners Cardiology/St. Rose Hospital
🇺🇸Las Vegas, Nevada, United States
The Ohio State
🇺🇸Columbus, Ohio, United States
Lancaster Heart and Stroke Foundation
🇺🇸Lancaster, Pennsylvania, United States
Sentara Norfolk Hospital
🇺🇸Norfolk, Virginia, United States
Aurora Health Care
🇺🇸Lake Geneva, Wisconsin, United States
MHH Klinik für Kardiologie und Angiologie
🇩🇪Hannover, Germany
Bnai-Zion Hospital
🇮🇱Haifa, Israel
Onze Lieve Vrouwziekenhuis
🇧🇪Aalst, Belgium
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Clinical Hosptial Centre Bezanijska Kosa
🇷🇸Belgrade, Serbia
Universitair Ziekenhuis Campus Gasthuisberg
🇧🇪Leuven, Belgium
Erasmus University Medical Center Rotterdam
🇳🇱Rotterdam, Netherlands
Medical University of Łodź
🇵🇱Łodź, Poland
Golden Jubilee National Hospital
🇬🇧Clydebank, Scotland, United Kingdom
Fourth Military Hospital Wroclaw
🇵🇱Wroclaw, Poland
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
South Denver Cardiology
🇺🇸Denver, Colorado, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Oklahoma Cardiovascular Research Group
🇺🇸Oklahoma City, Oklahoma, United States
VA Tennessee Valley Healthcare System
🇺🇸Nashville, Tennessee, United States
St. Louis Heart and Vascular
🇺🇸St Louis, Missouri, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Clearwater Cardiovascular Consultants/Morton Plant
🇺🇸Clearwater, Florida, United States
Florida Hospital, CV Research Institute
🇺🇸Orlando, Florida, United States
Cardiology Associates of North Mississippi
🇺🇸Tupelo, Mississippi, United States
Michigan Cardiovascular Institute
🇺🇸Saginaw, Michigan, United States
Beth Israel Deaconess
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Park Nicollet / Methodist
🇺🇸St. Louis Park, Minnesota, United States
Georgia Arrhythmia Consultants
🇺🇸Macon, Georgia, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
St. Luke's Mid America Heart Institute
🇺🇸Kansas City, Missouri, United States
Detroit Clinical Research Center/Botsford Hospital
🇺🇸Farmington Hills, Michigan, United States
United Heart & Vascular
🇺🇸Saint Paul, Minnesota, United States
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
University of Hull/Castle Hill Hospital
🇬🇧Cottingham, United Kingdom
University Hospital Coventry
🇬🇧Coventry, United Kingdom
Oxford University/John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Uniklinikum Aachen
🇩🇪Aachen, Germany
University of Medicine Mannheim
🇩🇪Mannheim, Germany
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Dallas Cardiovascular Associates (CRSTI)
🇺🇸Dallas, Texas, United States
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Multicare Health System
🇺🇸Tacoma, Washington, United States
Albertinen-Krankenhaus
🇩🇪Hamburg, Germany
St. Josef Hospital
🇩🇪Bochum, Germany
Ziekenhuis Oost Limburg
🇧🇪Genk, Belgium
University Medical Centre Groningen
🇳🇱Groningen, Netherlands
Lone Star Heart Center
🇺🇸Amarillo, Texas, United States
Texas Cardiac Arrhythmia (TCA)
🇺🇸Austin, Texas, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Charite Benjamin Franklin Campus
🇩🇪Berlin, Germany
Kootenai Heart Clinic
🇺🇸Spokane, Washington, United States
Uniklinikum Muenster
🇩🇪Muenster, Germany
EP Heart/ETHSC at Houston
🇺🇸Houston, Texas, United States
Asklepios St Georg Hospital
🇩🇪Hamburg, Germany
St. Peter's Hospital
🇬🇧Chertsey, United Kingdom
Glenfield Hospital
🇬🇧Leicester, United Kingdom
Clinical Centre of Serbia
🇷🇸Belgrade, Serbia
University of Utah
🇺🇸Salt Lake City, Utah, United States
Mount Sinai
🇺🇸New York, New York, United States
Munson Medical Center/Traverse Heart and Vascular
🇺🇸Traverse, Michigan, United States
Detroit Medical Center - Harper Hospital
🇺🇸Detroit, Michigan, United States
Banner Research Institute
🇺🇸Mesa, Arizona, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Montefiore Medical Center/Albert Einstein Colelge of Medicine
🇺🇸Bronx, New York, United States
Charite Campus Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Kardiologie
🇩🇪Berlin, Germany
Hershey Medical Center/Penn State
🇺🇸Hershey, Pennsylvania, United States
Sutter Memorial Hospital
🇺🇸Sacramento, California, United States
Royal Brompton Hospital
🇬🇧London, United Kingdom
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States