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Left Ventricular DysfunctionPhase 3INOVATE-HFNCT01303718

INcrease Of VAgal TonE in CHF

A Phase 3 study testing CardioFit® System in people with Left Ventricular Dysfunction and Heart Failure, run by BioControl Medical at 87 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Left Ventricular Dysfunction, Heart Failure
What is being tested?
CardioFit® System
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
730 participants
Where
87 sitesin 8 countries
Study dates
Feb 2011to Dec 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

87 sites in 8 countries.

87 sites in 8 countries

United States57 sites

  • Lone Star Heart Center

    Amarillo, Texas, 79106

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • St. Joseph's Hospital

    Atlanta, Georgia, 30342

  • Texas Cardiac Arrhythmia (TCA)

    Austin, Texas, 78705

  • University of Alabama Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess

    Boston, Massachusetts, 02215

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Cincinnati

    Cincinnati, Ohio, 45267-0542

  • Clearwater Cardiovascular Consultants/Morton Plant

    Clearwater, Florida, 33756

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • The Ohio State

    Columbus, Ohio, 43210

  • Dallas Cardiovascular Associates (CRSTI)

    Dallas, Texas, 75230

  • South Denver Cardiology

    Denver, Colorado, 80120

  • Detroit Medical Center - Harper Hospital

    Detroit, Michigan, 48201

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Detroit Clinical Research Center/Botsford Hospital

    Farmington Hills, Michigan, 48334

  • Glendale Memorial Hospital

    Glendale, California, 91204

  • Hershey Medical Center/Penn State

    Hershey, Pennsylvania, 17033

  • EP Heart/ETHSC at Houston

    Houston, Texas, 77030

  • St Lukes Episcopal

    Houston, Texas, 77030

  • Community Heart and Vascular Clinic

    Indianapolis, Indiana, 46250

  • Saint Vincent Medical Group

    Indianapolis, Indiana, 46260

  • University of Iowa

    Iowa City, Iowa, 52242

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • St. Luke's Mid America Heart Institute

    Kansas City, Missouri, 64111

  • Aurora Health Care

    Lake Geneva, Wisconsin, 53147

  • Lancaster Heart and Stroke Foundation

    Lancaster, Pennsylvania, 17602

  • Health Care Partners Cardiology/St. Rose Hospital

    Las Vegas, Nevada, 89169-2579

  • Bryan Heart Institute

    Lincoln, Nebraska, 68506

  • Georgia Arrhythmia Consultants

    Macon, Georgia, 31201

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Banner Research Institute

    Mesa, Arizona, 85206

  • VA Tennessee Valley Healthcare System

    Nashville, Tennessee, 37212

  • Mount Sinai

    New York, New York, 10029

  • Sentara Norfolk Hospital

    Norfolk, Virginia, 23507

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • Oklahoma Cardiovascular Research Group

    Oklahoma City, Oklahoma, 73120

  • Florida Hospital, CV Research Institute

    Orlando, Florida, 32803

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Sutter Memorial Hospital

    Sacramento, California, 95819

  • Michigan Cardiovascular Institute

    Saginaw, Michigan, 48601

  • Park Nicollet / Methodist

    Saint Louis Park, Minnesota, 55426

  • United Heart & Vascular

    Saint Paul, Minnesota, 55102

  • University of Utah

    Salt Lake City, Utah, 84132

  • Chula Vista Heart Clinic

    San Diego, California, 91910

  • Kootenai Heart Clinic

    Spokane, Washington, 99204

  • Washington University

    St Louis, Missouri, 63110

  • St. Louis Heart and Vascular

    St Louis, Missouri, 63136

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Multicare Health System

    Tacoma, Washington, 98405

  • Montefiore Medical Center/Albert Einstein Colelge of Medicine

    The Bronx, New York, 10467

  • Munson Medical Center/Traverse Heart and Vascular

    Traverse, Michigan, 49684

  • Cardiology Associates of North Mississippi

    Tupelo, Mississippi, 38801

Other trials in United States

United Kingdom10 sites

  • Queen Elizabeth Hospital

    Birmingham, B15 2TH

  • Blackpool Victoria Hospital

    Blackpool, FY3 8NR

  • St. Peter's Hospital

    Chertsey, KT16 0PZ

  • Golden Jubilee National Hospital

    Clydebank, Scotland, G81 4DY

  • University of Hull/Castle Hill Hospital

    Cottingham, HU16 5JQ

  • University Hospital Coventry

    Coventry, CV2 2DX

  • Glenfield Hospital

    Leicester, LE3 9QP

  • Royal Brompton Hospital

    London, SW3 6NP

  • Oxford University/John Radcliffe Hospital

    Oxford, OX3 9DU

  • Southampton General Hospital

    Southampton, SO16 6YD

Other trials in United Kingdom

Germany9 sites

  • Uniklinikum Aachen

    Aachen, 52074

  • Charite Benjamin Franklin Campus

    Berlin, 12203

  • Charite Campus Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Kardiologie

    Berlin, 13353

  • St. Josef Hospital

    Bochum, 44791

  • Asklepios St Georg Hospital

    Hamburg, 20099

  • Albertinen-Krankenhaus

    Hamburg, 22457

  • MHH Klinik für Kardiologie und Angiologie

    Hanover, 30625

  • University of Medicine Mannheim

    Mannheim, 68167

  • Uniklinikum Muenster

    Münster, 48149

Other trials in Germany

Belgium3 sites

  • Onze Lieve Vrouwziekenhuis

    Aalst, 9300

  • Ziekenhuis Oost Limburg

    Genk, 3600

  • Universitair Ziekenhuis Campus Gasthuisberg

    Leuven, 03000

Other trials in Belgium

Netherlands3 sites

  • University Medical Centre Groningen

    Groningen

  • Maastricht University Medical Center

    Maastricht

  • Erasmus University Medical Center Rotterdam

    Rotterdam, 3015 CE

Other trials in Netherlands

Poland2 sites

  • Medical University of Łodź

    Łodź, 91425

  • Fourth Military Hospital Wroclaw

    Wroclaw, 50981

Other trials in Poland

Serbia2 sites

  • Clinical Centre of Serbia

    Belgrade, 11000

  • Clinical Hosptial Centre Bezanijska Kosa

    Belgrade, 11080

Other trials in Serbia

Israel1 site

  • Bnai-Zion Hospital

    Haifa, 31048

Other trials in Israel

About this study

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

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.

Read the 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.

Being tested
CardioFit® System, Standard of Care
Keywords
LV Dysfunction, Heart Failure
Medical subject headings
Ventricular Dysfunction, Left, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CardioFit® SystemDevice

    Vagal nerve stimulation with the CardioFit® system

  • Standard of CareOther

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

Study groups in NCT01303718
Study groupRoleWhat they receive
CardioFit® SystemExperimentalVagal nerve stimulation with the CardioFit® system
Receives: Device: CardioFit® System
Standard of CareActive comparatorUsual care (no CardioFit System implant)
Receives: Other: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants reaching all-cause mortality or unplanned heart failure hospitalization or equivalent.

    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.

    Measured: Until the end of the study

  2. 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

    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

    Measured: a) 90 days and b) Until the end of the study

Secondary outcomes (7)

  1. The rate of unplanned heart failure hospitalization equivalents

    The rate of unplanned heart failure hospitalization equivalents

    Measured: Until the end of the study

  2. Mean improvement in LVESVi from baseline to 12-months

    Mean improvement in LVESVi from baseline to 12-months

    Measured: 12 Months

  3. Mean improvement in the summary score of the KCCQ from baseline to 12-months

    Mean improvement in the summary score of the KCCQ from baseline to 12-months

    Measured: 12 Months

  4. Mean improvement in 6 minute walk test from baseline to 12-months

    Mean improvement in 6 minute walk test from baseline to 12-months

    Measured: 12 Months

  5. All cause mortality and the number of unplanned heart failure hospitalization equivalents

    All cause mortality and the number of unplanned heart failure hospitalization equivalents

    Measured: Until the end of the study

  6. Rate of hospitalization-free days

    Rate of hospitalization-free days

    Measured: Until the end of the study

  7. Secondary Safety Endpoints: Mortality and Complications

    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

    Measured: Until the end of the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2011 (estimated)
  2. Study startFeb 2011
  3. Primary completionDec 2015
  4. Study completionDec 2015

Why it stopped: Futility of Primary Efficacy Endpoint

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
730 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01303718
Sponsor's protocol ID
CP-05-026
Acronym
INOVATE-HF
Status last verified
Dec 2015
First submitted
18 Feb 2011
Last updated
15 Dec 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27058909

  • 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.

    PubMed 22709747

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CardioFit® System in people with Left Ventricular Dysfunction and Heart Failure, run by BioControl Medical at 87 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 87 sites in United States, United Kingdom, Germany, Belgium, Netherlands and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Futility of Primary Efficacy Endpoint). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants reaching all-cause mortality or unplanned heart failure hospitalization or equivalent. (time frame: Until the end of the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01303718, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2015.

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