INOVATE-HF INcrease Of VAgal TonE in chronic Heart Failure


Status: Recruiting
Keywords: Heart Failure , Neurostimulator , Vagus Nerve
IRB Number: 00061054
Specialty: Cardiology, Cardiology, Cardiology, Cardiology
Sub Specialties: Interventional Cardiology, General Cardiology, Heart Failure

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.

The study objective is to determine the efficacy and safety of the CardioFit system for the treatment of subjects with systolic heart failure who have failed to achieve symptom relief through standard evidence-based management per applicable guidelines.

Cognitive Function Substudy

Show clinical difference in cognitive domain sub-scores from Baseline to 6 and 12 month visits.

Principal Investigator: Edward Gilbert
Department: Internal Medicine
Co Investigator: Stavros Drakos
Co Investigator: Jose Nativi-Nicolau
Co Investigator: Roger Freedman
Co Investigator: Josef Stehlik

Contact Information

Name:John Kirk
Phone: 801-585-2944

Inclusion Criteria

(1) Chronic symptomatic New York Heart Association functional class III heart failure.

(2) Age of at least 18 years.

(3) Subjects should be predominately in sinus rhythm at the time of enrollment. (Note: If the patient has a pacemaker or CRT device, a paced rhythm is acceptable.)

(4) On stable optimally uptitrated medical therapy recommended according to current guidelines as standard of care for heart failure therapy (refer to protocol Appendix C).

(5) LVEF < 40% per site measurement, within three months prior to enrollment

(6) The left ventricular end diastolic diameter, per site measurement, should be between 50 and 80 mm within 3 months prior to enrollment

(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 follow-up evaluations.

(9) Subjects with CRT devices may be included in the trial provided they have had CRT for at least 12 months (refer to INOVATE HF protocol for CRT optimization guidelines).

· NOTE: Subjects with CRT for less than 12 months or are anticipated to receive a CRT device within 12 months of randomization are excluded. Subjects with CRT who have had AV optimization, V-V optimization or LV lead repositioning in the last 3 months or expected in the next 3 months are excluded.

Exclusion Criteria

(1) Presence of a life threatening condition or disease other than heart failure, such as cancer, terminal renal failure or a progressive neurological disorder, 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 1 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 vagal nerve stimulation.

(4) Coronary Artery Bypass Surgery (CABG), valve replacement or repair, aortic surgery or percutaneous coronary intervention 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<50% predicted) or continuous oxygen dependence.

(13) 2nd or 3rd degree AV block or other pacemaker indication that is not treated with a pacemaker.

(14) Chronic (permanent) 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 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.