INcrease Of VAgal TonE in CHF

NCT ID: NCT01303718

Last Updated: 2015-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

730 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2015-12-31

Brief Summary

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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

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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.

Conditions

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Left Ventricular Dysfunction Heart Failure

Keywords

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LV Dysfunction Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CardioFit® System

Vagal nerve stimulation with the CardioFit® system

Group Type EXPERIMENTAL

CardioFit® System

Intervention Type DEVICE

Vagal nerve stimulation with the CardioFit® system

Standard of Care

Usual care (no CardioFit System implant)

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type OTHER

Usual care for LV dysfunction and heart failure (no CardioFit System implant)

Interventions

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CardioFit® System

Vagal nerve stimulation with the CardioFit® system

Intervention Type DEVICE

Standard of Care

Usual care for LV dysfunction and heart failure (no CardioFit System implant)

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioControl Medical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Douglas L. Mann, MD

Role: STUDY_CHAIR

Washington University School of Medicine

Michael Gold

Role: STUDY_CHAIR

Medical University of South Carolina

Locations

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University of Alabama Birmingham

Birmingham, Alabama, United States

Site Status

Banner Research Institute

Mesa, Arizona, United States

Site Status

Glendale Memorial Hospital

Glendale, California, United States

Site Status

Sutter Memorial Hospital

Sacramento, California, United States

Site Status

Chula Vista Heart Clinic

San Diego, California, United States

Site Status

South Denver Cardiology

Denver, Colorado, United States

Site Status

Clearwater Cardiovascular Consultants/Morton Plant

Clearwater, Florida, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Hospital, CV Research Institute

Orlando, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

St. Joseph's Hospital

Atlanta, Georgia, United States

Site Status

Georgia Arrhythmia Consultants

Macon, Georgia, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

Community Heart and Vascular Clinic

Indianapolis, Indiana, United States

Site Status

Saint Vincent Medical Group

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Detroit Medical Center - Harper Hospital

Detroit, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Detroit Clinical Research Center/Botsford Hospital

Farmington Hills, Michigan, United States

Site Status

Michigan Cardiovascular Institute

Saginaw, Michigan, United States

Site Status

Munson Medical Center/Traverse Heart and Vascular

Traverse, Michigan, United States

Site Status

Park Nicollet / Methodist

Saint Louis Park, Minnesota, United States

Site Status

United Heart & Vascular

Saint Paul, Minnesota, United States

Site Status

Cardiology Associates of North Mississippi

Tupelo, Mississippi, United States

Site Status

St. Luke's Mid America Heart Institute

Kansas City, Missouri, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

St. Louis Heart and Vascular

St Louis, Missouri, United States

Site Status

Bryan Heart Institute

Lincoln, Nebraska, United States

Site Status

Health Care Partners Cardiology/St. Rose Hospital

Las Vegas, Nevada, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Montefiore Medical Center/Albert Einstein Colelge of Medicine

The Bronx, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

The Ohio State

Columbus, Ohio, United States

Site Status

Oklahoma Cardiovascular Research Group

Oklahoma City, Oklahoma, United States

Site Status

Hershey Medical Center/Penn State

Hershey, Pennsylvania, United States

Site Status

Lancaster Heart and Stroke Foundation

Lancaster, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

VA Tennessee Valley Healthcare System

Nashville, Tennessee, United States

Site Status

Lone Star Heart Center

Amarillo, Texas, United States

Site Status

Texas Cardiac Arrhythmia (TCA)

Austin, Texas, United States

Site Status

Dallas Cardiovascular Associates (CRSTI)

Dallas, Texas, United States

Site Status

EP Heart/ETHSC at Houston

Houston, Texas, United States

Site Status

St Lukes Episcopal

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Sentara Norfolk Hospital

Norfolk, Virginia, United States

Site Status

Kootenai Heart Clinic

Spokane, Washington, United States

Site Status

Multicare Health System

Tacoma, Washington, United States

Site Status

Aurora Health Care

Lake Geneva, Wisconsin, United States

Site Status

Marshfield Clinic

Marshfield, Wisconsin, United States

Site Status

Onze Lieve Vrouwziekenhuis

Aalst, , Belgium

Site Status

Ziekenhuis Oost Limburg

Genk, , Belgium

Site Status

Universitair Ziekenhuis Campus Gasthuisberg

Leuven, , Belgium

Site Status

Uniklinikum Aachen

Aachen, , Germany

Site Status

Charite Benjamin Franklin Campus

Berlin, , Germany

Site Status

Charite Campus Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Kardiologie

Berlin, , Germany

Site Status

St. Josef Hospital

Bochum, , Germany

Site Status

Asklepios St Georg Hospital

Hamburg, , Germany

Site Status

Albertinen-Krankenhaus

Hamburg, , Germany

Site Status

MHH Klinik für Kardiologie und Angiologie

Hanover, , Germany

Site Status

University of Medicine Mannheim

Mannheim, , Germany

Site Status

Uniklinikum Muenster

Münster, , Germany

Site Status

Bnai-Zion Hospital

Haifa, , Israel

Site Status

University Medical Centre Groningen

Groningen, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Erasmus University Medical Center Rotterdam

Rotterdam, , Netherlands

Site Status

Fourth Military Hospital Wroclaw

Wroclaw, , Poland

Site Status

Medical University of Łodź

Łodź, , Poland

Site Status

Clinical Centre of Serbia

Belgrade, , Serbia

Site Status

Clinical Hosptial Centre Bezanijska Kosa

Belgrade, , Serbia

Site Status

Golden Jubilee National Hospital

Clydebank, Scotland, United Kingdom

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Blackpool Victoria Hospital

Blackpool, , United Kingdom

Site Status

St. Peter's Hospital

Chertsey, , United Kingdom

Site Status

University of Hull/Castle Hill Hospital

Cottingham, , United Kingdom

Site Status

University Hospital Coventry

Coventry, , United Kingdom

Site Status

Glenfield Hospital

Leicester, , United Kingdom

Site Status

Royal Brompton Hospital

London, , United Kingdom

Site Status

Oxford University/John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Belgium Germany Israel Netherlands Poland Serbia United Kingdom

References

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Gold MR, Van Veldhuisen DJ, Hauptman PJ, Borggrefe M, Kubo SH, Lieberman RA, Milasinovic G, Berman BJ, Djordjevic S, Neelagaru S, Schwartz PJ, Starling RC, Mann DL. Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial. J Am Coll Cardiol. 2016 Jul 12;68(2):149-58. doi: 10.1016/j.jacc.2016.03.525. Epub 2016 Apr 4.

Reference Type DERIVED
PMID: 27058909 (View on PubMed)

Hauptman PJ, Schwartz PJ, Gold MR, Borggrefe M, Van Veldhuisen DJ, Starling RC, Mann DL. Rationale and study design of the increase of vagal tone in heart failure study: INOVATE-HF. Am Heart J. 2012 Jun;163(6):954-962.e1. doi: 10.1016/j.ahj.2012.03.021.

Reference Type DERIVED
PMID: 22709747 (View on PubMed)

Related Links

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http://clinicaltrials.gov/ct2/show/NCT00461019

CardioFit Pilot Study Description and Results

Other Identifiers

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CP-05-026

Identifier Type: -

Identifier Source: org_study_id