Trial record 1 of 1 for:    INOVATE-HF
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INcrease Of VAgal TonE in CHF (INOVATE-HF)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
BioControl Medical Identifier:
First received: February 18, 2011
Last updated: November 17, 2015
Last verified: November 2015
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.

Condition Intervention Phase
Left Ventricular Dysfunction
Heart Failure
Device: CardioFit® System
Other: Standard of Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: INcrease Of VAgal TonE in CHF (INOVATE-HF) - A Randomized Study to Establish the Safety and Efficacy of CardioFit® for the Treatment of Subjects With Heart Failure and Left Ventricular Dysfunction

Resource links provided by NLM:

Further study details as provided by BioControl Medical:

Primary Outcome Measures:
  • Number of participants reaching all-cause mortality or unplanned heart failure hospitalization or equivalent. [ Time Frame: Until the end of the study ] [ Designated as safety issue: No ]
    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 [ Time Frame: a) 90 days and b) Until the end of the study ] [ Designated as safety issue: Yes ]

    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:
  • The rate of unplanned heart failure hospitalization equivalents [ Time Frame: Until the end of the study ] [ Designated as safety issue: No ]
    The rate of unplanned heart failure hospitalization equivalents

  • Mean improvement in LVESVi from baseline to 12-months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Mean improvement in LVESVi from baseline to 12-months

  • Mean improvement in the summary score of the KCCQ from baseline to 12-months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Mean improvement in 6 minute walk test from baseline to 12-months

  • All cause mortality and the number of unplanned heart failure hospitalization equivalents [ Time Frame: Until the end of the study ] [ Designated as safety issue: No ]
    All cause mortality and the number of unplanned heart failure hospitalization equivalents

  • Rate of hospitalization-free days [ Time Frame: Until the end of the study ] [ Designated as safety issue: No ]
    Rate of hospitalization-free days

  • Secondary Safety Endpoints: Mortality and Complications [ Time Frame: Until the end of the study ] [ Designated as safety issue: Yes ]

    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

Estimated Enrollment: 650
Study Start Date: February 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CardioFit® System
Vagal nerve stimulation with the CardioFit® system
Device: CardioFit® System
Vagal nerve stimulation with the CardioFit® system
Active Comparator: Standard of Care
Usual care (no CardioFit System implant)
Other: Standard of Care
Usual care for LV dysfunction and heart failure (no CardioFit System implant)

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Chronic symptomatic heart failure in New York Heart Association functional class III.
  2. Age of at least 18 years.
  3. Subjects should be predominately in sinus rhythm at the time of enrollment.
  4. On stable optimally uptitrated medical therapy recommended according to current guidelines as standard of care for heart failure therapy.
  5. LVEF ≤ 40% per site measurement within three months before enrollment.
  6. The left ventricular end diastolic diameter, per site measurement, should be between 50 and 80 mm.
  7. The subject is a male or postmenopausal female. Females of childbearing age may be included if an acceptable contraception measure is used.
  8. Subject must sign an approved informed consent form. Subject agrees to attend all followup evaluations.
  9. Subjects with CRT devices may be included in the trial provided they have had CRT for at least 12 months.

Exclusion Criteria:

  1. Presence of a life threatening condition or disease other than heart failure, that is likely to lead to death within 6 months.
  2. Acute myocardial infarction (MI), variant angina pectoris, unstable angina or acute coronary syndrome in the previous one month.
  3. 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.
  4. Coronary Artery Bypass Surgery (CABG), valve replacement or repair, aortic surgery or PCI) in the prior 3 months or planned/anticipated within 6 months.
  5. Heart failure due to acute myocarditis, restrictive cardiomyopathy, constrictive pericarditis or hemodynamically significant aortic valve insufficiency, aortic stenosis, or mitral valve stenosis.
  6. Severe renal failure (creatinine level > 3 mg/dL (265 micromole/liter).
  7. Severe hepatic failure (transaminase level four times ULN, or total bilirubin level > 1.8 mmol/dL).
  8. 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.
  9. 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.
  10. Current hypotension (systolic blood pressure below 80 mmHg).
  11. Active peptic ulcer disease or history of upper GI bleeding, or ulcer within 6 months.
  12. History of lung disease such as severe asthma, COPD (e.g., FEV1<1.5 liter) or continuous oxygen dependence.
  13. 2nd or 3rd degree AV block or other pacemaker indication that is not treated with a pacemaker.
  14. 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.
  15. Use of unipolar sensing
  16. Congenital or acquired long QT syndrome.
  17. Documented recorded or suspected vaso-vagal syncope or vaso depressor syncope.
  18. Treatment by investigational drug or device within the past 3 months.
  19. 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.
  20. 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.
  21. 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.
  22. Immunosuppressed subjects; subjects under systemic steroid treatment.
  23. 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.
  24. Untreated obstructive sleep apnea ("OSA") with apnea-hypopnea index of 15 or more; or OSA that is treated for less than 3-months.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01303718

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United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Banner Research Institute
Mesa, Arizona, United States, 85206
United States, California
Glendale Memorial Hospital
Glendale, California, United States, 91204
Sutter Memorial Hospital
Sacramento, California, United States, 95819
Chula Vista Heart Clinic
San Diego, California, United States, 91910
United States, Colorado
South Denver Cardiology
Denver, Colorado, United States, 80120
United States, Florida
Clearwater Cardiovascular Consultants/Morton Plant
Clearwater, Florida, United States, 33756
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
Florida Hospital, CV Research Institute
Orlando, Florida, United States, 32803
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
St. Joseph's Hospital
Atlanta, Georgia, United States, 30342
Georgia Arrhythmia Consultants
Macon, Georgia, United States, 31201
United States, Illinois
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453
United States, Indiana
Community Heart and Vascular Clinic
Indianapolis, Indiana, United States, 46250
Saint Vincent Medical Group
Indianapolis, Indiana, United States, 46260
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Beth Israel Deaconess
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Detroit Medical Center - Harper Hospital
Detroit, Michigan, United States, 48201
Henry Ford Health System
Detroit, Michigan, United States, 48202
Detroit Clinical Research Center/Botsford Hospital
Farmington Hills, Michigan, United States, 48334
Michigan Cardiovascular Institute
Saginaw, Michigan, United States, 48601
Munson Medical Center/Traverse Heart and Vascular
Traverse, Michigan, United States, 49684
United States, Minnesota
United Heart & Vascular
Saint Paul, Minnesota, United States, 55102
Park Nicollet / Methodist
St. Louis Park, Minnesota, United States, 55426
United States, Mississippi
Cardiology Associates of North Mississippi
Tupelo, Mississippi, United States, 38801
United States, Missouri
St. Luke's Mid America Heart Institute
Kansas City, Missouri, United States, 64111
St. Louis Heart and Vascular
St Louis, Missouri, United States, 63136
Washington University
St. Louis, Missouri, United States, 63110
United States, Nebraska
Bryan Heart Institute
Lincoln, Nebraska, United States, 68506
United States, Nevada
Health Care Partners Cardiology/St. Rose Hospital
Las Vegas, Nevada, United States, 89169-2579
United States, New York
Montefiore Medical Center/Albert Einstein Colelge of Medicine
Bronx, New York, United States, 10467
Mount Sinai
New York, New York, United States, 10029
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0542
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
The Ohio State
Columbus, Ohio, United States, 43210
United States, Oklahoma
Oklahoma Cardiovascular Research Group
Oklahoma City, Oklahoma, United States, 73120
United States, Pennsylvania
Hershey Medical Center/Penn State
Hershey, Pennsylvania, United States, 17033
Lancaster Heart and Stroke Foundation
Lancaster, Pennsylvania, United States, 17602
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
VA Tennessee Valley Healthcare System
Nashville, Tennessee, United States, 37212
United States, Texas
Lone Star Heart Center
Amarillo, Texas, United States, 79106
Texas Cardiac Arrhythmia (TCA)
Austin, Texas, United States, 78705
Dallas Cardiovascular Associates (CRSTI)
Dallas, Texas, United States, 75230
EP Heart/ETHSC at Houston
Houston, Texas, United States, 77030
St Lukes Episcopal
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
Sentara Norfolk Hospital
Norfolk, Virginia, United States, 23507
United States, Washington
Kootenai Heart Clinic
Spokane, Washington, United States, 99204
Multicare Health System
Tacoma, Washington, United States, 98405
United States, Wisconsin
Aurora Health Care
Lake Geneva, Wisconsin, United States, 53147
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Onze Lieve Vrouwziekenhuis
Aalst, Belgium, 9300
Ziekenhuis Oost Limburg
Genk, Belgium, 3600
Universitair Ziekenhuis Campus Gasthuisberg
Leuven, Belgium, 03000
Uniklinikum Aachen
Aachen, Germany, 52074
Charite Benjamin Franklin Campus
Berlin, Germany, 12203
Charite Campus Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Kardiologie
Berlin, Germany, 13353
St. Josef Hospital
Bochum, Germany, 44791
Hamburg, Germany, 22457
Asklepios St Georg Hospital
Hamburg, Germany, 20099
MHH Klinik für Kardiologie und Angiologie
Hannover, Germany, 30625
University of Medicine Mannheim
Mannheim, Germany, 68167
Uniklinikum Muenster
Muenster, Germany, 48149
Bnai-Zion Hospital
Haifa, Israel, 31048
University Medical Centre Groningen
Groningen, Netherlands
Maastricht University Medical Center
Maastricht, Netherlands
Erasmus University Medical Center Rotterdam
Rotterdam, Netherlands, 3015 CE
Fourth Military Hospital Wroclaw
Wroclaw, Poland, 50981
Medical University of Łodź
Łodź, Poland, 91425
Clinical Centre of Serbia
Belgrade, Serbia, 11000
Clinical Hosptial Centre Bezanijska Kosa
Belgrade, Serbia, 11080
United Kingdom
Golden Jubilee National Hospital
Clydebank, Scotland, United Kingdom, G81 4DY
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
Blackpool Victoria Hospital
Blackpool, United Kingdom, FY3 8NR
St. Peter's Hospital
Chertsey, United Kingdom, KT16 0PZ
University of Hull/Castle Hill Hospital
Cottingham, United Kingdom, HU16 5JQ
University Hospital Coventry
Coventry, United Kingdom, CV2 2DX
Glenfield Hospital
Leicester, United Kingdom, LE3 9QP
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Oxford University/John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
BioControl Medical
Study Chair: Douglas L. Mann, MD Washington University School of Medicine
Study Chair: Michael Gold Medical University of South Carolina
  More Information

Additional Information:
No publications provided by BioControl Medical

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: BioControl Medical Identifier: NCT01303718     History of Changes
Other Study ID Numbers: CP-05-026
Study First Received: February 18, 2011
Last Updated: November 17, 2015
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by BioControl Medical:
LV Dysfunction
Heart Failure

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction
Ventricular Dysfunction, Left
Cardiovascular Diseases
Heart Diseases processed this record on November 25, 2015