INcrease Of VAgal TonE in CHF

Heart Failure Clinical Trial

— INOVATE-HF  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01303718
• Other study ID #: CP-05-026
• Status: Terminated
• Phase: Phase 3
• First received: February 18, 2011
• Last updated: December 11, 2015
• Start date: February 2011
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: BioControl Medical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 730
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Left Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Device:
• CardioFit® System
Vagal nerve stimulation with the CardioFit® system

Other:
• Standard of Care
Usual care for LV dysfunction and heart failure (no CardioFit System implant)

Locations

Country	Name	City	State
Belgium	Onze Lieve Vrouwziekenhuis	Aalst
Belgium	Ziekenhuis Oost Limburg	Genk
Belgium	Universitair Ziekenhuis Campus Gasthuisberg	Leuven
Germany	Uniklinikum Aachen	Aachen
Germany	Charite Benjamin Franklin Campus	Berlin
Germany	Charite Campus Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Kardiologie	Berlin
Germany	St. Josef Hospital	Bochum
Germany	Albertinen-Krankenhaus	Hamburg
Germany	Asklepios St Georg Hospital	Hamburg
Germany	MHH Klinik für Kardiologie und Angiologie	Hannover
Germany	University of Medicine Mannheim	Mannheim
Germany	Uniklinikum Muenster	Muenster
Israel	Bnai-Zion Hospital	Haifa
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Erasmus University Medical Center Rotterdam	Rotterdam
Poland	Medical University of Lodz	Lodz
Poland	Fourth Military Hospital Wroclaw	Wroclaw
Serbia	Clinical Centre of Serbia	Belgrade
Serbia	Clinical Hosptial Centre Bezanijska Kosa	Belgrade
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	St. Peter's Hospital	Chertsey
United Kingdom	Golden Jubilee National Hospital	Clydebank	Scotland
United Kingdom	University of Hull/Castle Hill Hospital	Cottingham
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Oxford University/John Radcliffe Hospital	Oxford
United Kingdom	Southampton General Hospital	Southampton
United States	Lone Star Heart Center	Amarillo	Texas
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	St. Joseph's Hospital	Atlanta	Georgia
United States	Texas Cardiac Arrhythmia (TCA)	Austin	Texas
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center/Albert Einstein Colelge of Medicine	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Clearwater Cardiovascular Consultants/Morton Plant	Clearwater	Florida
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	The Ohio State	Columbus	Ohio
United States	Dallas Cardiovascular Associates (CRSTI)	Dallas	Texas
United States	South Denver Cardiology	Denver	Colorado
United States	Detroit Medical Center - Harper Hospital	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	Detroit Clinical Research Center/Botsford Hospital	Farmington Hills	Michigan
United States	Glendale Memorial Hospital	Glendale	California
United States	Hershey Medical Center/Penn State	Hershey	Pennsylvania
United States	EP Heart/ETHSC at Houston	Houston	Texas
United States	St Lukes Episcopal	Houston	Texas
United States	Community Heart and Vascular Clinic	Indianapolis	Indiana
United States	Saint Vincent Medical Group	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	St. Luke's Mid America Heart Institute	Kansas City	Missouri
United States	Aurora Health Care	Lake Geneva	Wisconsin
United States	Lancaster Heart and Stroke Foundation	Lancaster	Pennsylvania
United States	Health Care Partners Cardiology/St. Rose Hospital	Las Vegas	Nevada
United States	Bryan Heart Institute	Lincoln	Nebraska
United States	Georgia Arrhythmia Consultants	Macon	Georgia
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Banner Research Institute	Mesa	Arizona
United States	VA Tennessee Valley Healthcare System	Nashville	Tennessee
United States	Mount Sinai	New York	New York
United States	Sentara Norfolk Hospital	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Oklahoma Cardiovascular Research Group	Oklahoma City	Oklahoma
United States	Florida Hospital, CV Research Institute	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Sutter Memorial Hospital	Sacramento	California
United States	Michigan Cardiovascular Institute	Saginaw	Michigan
United States	United Heart & Vascular	Saint Paul	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	Chula Vista Heart Clinic	San Diego	California
United States	Kootenai Heart Clinic	Spokane	Washington
United States	St. Louis Heart and Vascular	St Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	Park Nicollet / Methodist	St. Louis Park	Minnesota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Multicare Health System	Tacoma	Washington
United States	Munson Medical Center/Traverse Heart and Vascular	Traverse	Michigan
United States	Cardiology Associates of North Mississippi	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
BioControl Medical

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Israel,  Netherlands,  Poland,  Serbia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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: Freedom from procedure and system related complication events through 90 days; 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	Yes
Secondary	The rate of unplanned heart failure hospitalization equivalents	The rate of unplanned heart failure hospitalization equivalents	Until the end of the study	No
Secondary	Mean improvement in LVESVi from baseline to 12-months	Mean improvement in LVESVi from baseline to 12-months	12 Months	No
Secondary	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	12 Months	No
Secondary	Mean improvement in 6 minute walk test from baseline to 12-months	Mean improvement in 6 minute walk test from baseline to 12-months	12 Months	No
Secondary	All cause mortality and the number of unplanned heart failure hospitalization equivalents	All cause mortality and the number of unplanned heart failure hospitalization equivalents	Until the end of the study	No
Secondary	Rate of hospitalization-free days	Rate of hospitalization-free days	Until the end of the study	No
Secondary	Secondary Safety Endpoints: Mortality and Complications	The following additional (secondary) safety endpoint data will also be evaluated comparatively at 6- and 12-months: All-cause mortality; Cardiovascular mortality; Serious adverse events; Complications; System- or procedure-related complications	Until the end of the study	Yes

External Links

•   CardioFit Pilot Study Description and Results