Study Stopped
Futility of Primary Efficacy Endpoint
INcrease Of VAgal TonE in CHF
INOVATE-HF
1 other identifier
interventional
730
8 countries
87
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2011
Longer than P75 for phase_3
87 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2011
CompletedFirst Submitted
Initial submission to the registry
February 18, 2011
CompletedFirst Posted
Study publicly available on registry
February 25, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2015
CompletedDecember 15, 2015
December 1, 2015
4.8 years
February 18, 2011
December 11, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
Until the end of the study
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
a) 90 days and b) Until the end of the study
Secondary Outcomes (7)
The rate of unplanned heart failure hospitalization equivalents
Until the end of the study
Mean improvement in LVESVi from baseline to 12-months
12 Months
Mean improvement in the summary score of the KCCQ from baseline to 12-months
12 Months
Mean improvement in 6 minute walk test from baseline to 12-months
12 Months
All cause mortality and the number of unplanned heart failure hospitalization equivalents
Until the end of the study
- +2 more secondary outcomes
Study Arms (2)
CardioFit® System
EXPERIMENTALVagal nerve stimulation with the CardioFit® system
Standard of Care
ACTIVE COMPARATORUsual care (no CardioFit System implant)
Interventions
Usual care for LV dysfunction and heart failure (no CardioFit System implant)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- nd 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
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (87)
University of Alabama Birmingham
Birmingham, Alabama, 35294, United States
Banner Research Institute
Mesa, Arizona, 85206, United States
Glendale Memorial Hospital
Glendale, California, 91204, United States
Sutter Memorial Hospital
Sacramento, California, 95819, United States
Chula Vista Heart Clinic
San Diego, California, 91910, United States
South Denver Cardiology
Denver, Colorado, 80120, United States
Clearwater Cardiovascular Consultants/Morton Plant
Clearwater, Florida, 33756, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Florida Hospital, CV Research Institute
Orlando, Florida, 32803, United States
Emory University
Atlanta, Georgia, 30322, United States
St. Joseph's Hospital
Atlanta, Georgia, 30342, United States
Georgia Arrhythmia Consultants
Macon, Georgia, 31201, United States
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453, United States
Community Heart and Vascular Clinic
Indianapolis, Indiana, 46250, United States
Saint Vincent Medical Group
Indianapolis, Indiana, 46260, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Detroit Medical Center - Harper Hospital
Detroit, Michigan, 48201, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Detroit Clinical Research Center/Botsford Hospital
Farmington Hills, Michigan, 48334, United States
Michigan Cardiovascular Institute
Saginaw, Michigan, 48601, United States
Munson Medical Center/Traverse Heart and Vascular
Traverse, Michigan, 49684, United States
Park Nicollet / Methodist
Saint Louis Park, Minnesota, 55426, United States
United Heart & Vascular
Saint Paul, Minnesota, 55102, United States
Cardiology Associates of North Mississippi
Tupelo, Mississippi, 38801, United States
St. Luke's Mid America Heart Institute
Kansas City, Missouri, 64111, United States
Washington University
St Louis, Missouri, 63110, United States
St. Louis Heart and Vascular
St Louis, Missouri, 63136, United States
Bryan Heart Institute
Lincoln, Nebraska, 68506, United States
Health Care Partners Cardiology/St. Rose Hospital
Las Vegas, Nevada, 89169-2579, United States
Mount Sinai
New York, New York, 10029, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Montefiore Medical Center/Albert Einstein Colelge of Medicine
The Bronx, New York, 10467, United States
University of Cincinnati
Cincinnati, Ohio, 45267-0542, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
The Ohio State
Columbus, Ohio, 43210, United States
Oklahoma Cardiovascular Research Group
Oklahoma City, Oklahoma, 73120, United States
Hershey Medical Center/Penn State
Hershey, Pennsylvania, 17033, United States
Lancaster Heart and Stroke Foundation
Lancaster, Pennsylvania, 17602, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
VA Tennessee Valley Healthcare System
Nashville, Tennessee, 37212, United States
Lone Star Heart Center
Amarillo, Texas, 79106, United States
Texas Cardiac Arrhythmia (TCA)
Austin, Texas, 78705, United States
Dallas Cardiovascular Associates (CRSTI)
Dallas, Texas, 75230, United States
EP Heart/ETHSC at Houston
Houston, Texas, 77030, United States
St Lukes Episcopal
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Sentara Norfolk Hospital
Norfolk, Virginia, 23507, United States
Kootenai Heart Clinic
Spokane, Washington, 99204, United States
Multicare Health System
Tacoma, Washington, 98405, United States
Aurora Health Care
Lake Geneva, Wisconsin, 53147, United States
Marshfield Clinic
Marshfield, Wisconsin, 54449, United States
Onze Lieve Vrouwziekenhuis
Aalst, 9300, Belgium
Ziekenhuis Oost Limburg
Genk, 3600, Belgium
Universitair Ziekenhuis Campus Gasthuisberg
Leuven, 03000, Belgium
Uniklinikum Aachen
Aachen, 52074, Germany
Charite Benjamin Franklin Campus
Berlin, 12203, Germany
Charite Campus Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Kardiologie
Berlin, 13353, Germany
St. Josef Hospital
Bochum, 44791, Germany
Asklepios St Georg Hospital
Hamburg, 20099, Germany
Albertinen-Krankenhaus
Hamburg, 22457, Germany
MHH Klinik für Kardiologie und Angiologie
Hanover, 30625, Germany
University of Medicine Mannheim
Mannheim, 68167, Germany
Uniklinikum Muenster
Münster, 48149, Germany
Bnai-Zion Hospital
Haifa, 31048, Israel
University Medical Centre Groningen
Groningen, Netherlands
Maastricht University Medical Center
Maastricht, Netherlands
Erasmus University Medical Center Rotterdam
Rotterdam, 3015 CE, Netherlands
Fourth Military Hospital Wroclaw
Wroclaw, 50981, Poland
Medical University of Łodź
Łodź, 91425, Poland
Clinical Centre of Serbia
Belgrade, 11000, Serbia
Clinical Hosptial Centre Bezanijska Kosa
Belgrade, 11080, Serbia
Golden Jubilee National Hospital
Clydebank, Scotland, G81 4DY, United Kingdom
Queen Elizabeth Hospital
Birmingham, B15 2TH, United Kingdom
Blackpool Victoria Hospital
Blackpool, FY3 8NR, United Kingdom
St. Peter's Hospital
Chertsey, KT16 0PZ, United Kingdom
University of Hull/Castle Hill Hospital
Cottingham, HU16 5JQ, United Kingdom
University Hospital Coventry
Coventry, CV2 2DX, United Kingdom
Glenfield Hospital
Leicester, LE3 9QP, United Kingdom
Royal Brompton Hospital
London, SW3 6NP, United Kingdom
Oxford University/John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
Related Publications (2)
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.
PMID: 27058909DERIVEDHauptman 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.
PMID: 22709747DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Douglas L. Mann, MD
Washington University School of Medicine
- STUDY CHAIR
Michael Gold
Medical University of South Carolina
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 18, 2011
First Posted
February 25, 2011
Study Start
February 1, 2011
Primary Completion
December 1, 2015
Study Completion
December 1, 2015
Last Updated
December 15, 2015
Record last verified: 2015-12