Neural Cardiac Therapy for Heart Failure Study (NECTAR-HF)

Not Applicable

Active, not recruiting

Conditions: Congestive Heart Failure
Heart Failure

Interventions: Device: Implant of investigational device system
Procedure: Titration during the randomization phase
Diagnostic Test: Blood Draw
Procedure: Titration after the randomization phase

Registration Number: NCT01385176

Lead Sponsor: Boston Scientific Corporation

Brief Summary: The NECTAR-HF feasibility trial is designed to evaluate the application of right vagal nerve stimulation in heart failure patients with a New York Heart Association Class III, an ejection fraction equal to or less than 35 %, and a narrow QRS duration equal to or less than 130 ms.

Detailed Description: The objectives of this study are to assess the impact of right vagal nerve stimulation on left ventricular remodeling, functional capacity, quality of life, and other measures in heart failure patients over a 6-month period. In addition, the study will assess the safety of the NECTAR-HF study system over an 18-month period.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 118

Inclusion Criteria

Age 18 or above, and of legal age to give informed consent specific to national laws
Willing and capable of providing informed consent
Capable of participating in all testing associated with this clinical investigation
Stable symptomatic heart failure NYHA class II-III
Left ventricular (LV) ejection fraction equal or smaller than 35 %
Left ventricular end diastolic diameter (LVEDD) of 5.5 cm or greater
Prescribed to optimal pharmacologic therapy

Exclusion Criteria

QRS larger than 130 ms
Patients who have been hospitalized for heart failure and who required the use of HF IV therapy within 30 days before enrollment
Patients unable to tolerate anesthesia required for implant
Patients with unstable angina, myocardial infarction, PTCA, coronary artery bypass graft, cerebral vascular accident, or transient ischemic attack within previous 90 days before enrollment
Patients whose primary cause of heart failure is mitral or aortic valve disease, with a severe classification
Patients with persistent or permanent atrial fibrillation within 90 days prior to enrollment
Pacemaker indicated patients
Patients whose heart failure is due to congenital heart disease
Patients who have started treatment for sleep apnea or sleep disordered breathing with therapies to maintain airway patency (e.g., CPAP, Bi-PAP,APAP) with or without oxygen supplementation within the previous 6 months prior to enrollment
Patients with hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis)
Patients with documented chronic obstructive lung disease
Patients on or indicated for renal dialysis
Type 1 diabetic patients
Type 2 diabetic patients that have been treated with insulin for more than 5 years prior to enrollment
Patients with a life expectancy of less than 12 months per physician judgment
Patients involved in any concurrent clinical investigation
Women of childbearing potential who are or might be pregnant at the time of the study or breastfeeding
Patients with a prior cardiac transplant or expecting a heart transplant operation within the next 12 months
Patients with a prior vagotomy
Patients with prior or existing vagal nerve stimulation treatment
Patients implanted with any active implantable medical device other than a left sided single or dual chamber implantable cardioverter defibrillator (ICD) with bipolar sensing, or a left sided CRT device with each sensing channel programmed to either bipolar sensing or no sensing. All CRT patients must have had CRT for at least 1 year prior to enrollment. The total number of CRT patients will not exceed 30
Patients with locally implanted semi-/permanent devices such as vascular catheters, etc. that would interfere with the NECTAR-HF study system
Patients with previously implanted devices on the right side that became infected before removal
Patients with previous neck surgery and resultant scar formation that interferes with the ability to implant the study system on the right side of the neck (Thyroid/parathyroid, carotid artery etc)
Patients with known recurrent nerve paralysis
Patients who have undergone radiotherapy for thyroid disease/cancer
Patients who have existing or prior tracheotomy
Patients with severe vertebral cervical disease and limited mobility in the neck; includes those that frequently wear a brace
Patients with carotid murmur/vascular bruit/carotid artery lesion
Patients with known/suspected vascular malformation in carotid/vertebral circulatory bed
Patients who are likely to need an MRI of the neck area because of previous medical conditions

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Therapy	Titration during the randomization phase	Implant of investigational device system for vagus nerve stimulation. Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The experimental arm was receiving vagus nerve stimulation during the first 6 months after implant. Titration during the randomization phase with delivery of highest tolerable by patient stimulation current. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.
Therapy	Implant of investigational device system	Implant of investigational device system for vagus nerve stimulation. Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The experimental arm was receiving vagus nerve stimulation during the first 6 months after implant. Titration during the randomization phase with delivery of highest tolerable by patient stimulation current. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.
Control	Blood Draw	Implant of investigational device system for vagus nerve stimulation. Control group was implanted with study system like the experimental arm, but was not receiving experimental vagus nerve stimulation therapy during the first 6 months after implant. 6-month after implant a cross-over took place and the control arm also started to receive experimental vagus nerve stimulation. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.
Therapy	Titration after the randomization phase	Implant of investigational device system for vagus nerve stimulation. Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The experimental arm was receiving vagus nerve stimulation during the first 6 months after implant. Titration during the randomization phase with delivery of highest tolerable by patient stimulation current. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.
Therapy	Blood Draw	Implant of investigational device system for vagus nerve stimulation. Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The experimental arm was receiving vagus nerve stimulation during the first 6 months after implant. Titration during the randomization phase with delivery of highest tolerable by patient stimulation current. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.
Control	Implant of investigational device system	Implant of investigational device system for vagus nerve stimulation. Control group was implanted with study system like the experimental arm, but was not receiving experimental vagus nerve stimulation therapy during the first 6 months after implant. 6-month after implant a cross-over took place and the control arm also started to receive experimental vagus nerve stimulation. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.
Control	Titration after the randomization phase	Implant of investigational device system for vagus nerve stimulation. Control group was implanted with study system like the experimental arm, but was not receiving experimental vagus nerve stimulation therapy during the first 6 months after implant. 6-month after implant a cross-over took place and the control arm also started to receive experimental vagus nerve stimulation. Blood Draw before implant and 6 months after implant. Titration after the randomization phase with adjustments of the chronically highest tolearble by patient current.

Primary Outcome Measures

Name	Time	Method
Percentage of Surviving Participants	18-months	As pre-specified in the study protocol, the All-cause Survival endpoint combined both groups into one analysis population. Subjects contributed data according to the follow-up period during they received VNS therapy (Implant through 18 months for Therapy subjects, 6 through 18 months for Control subjects). Control patients who exited the study in the first 6 months, or who did not have a 6 month visit, were excluded.
Change in Left Ventricular End-systolic Dimension (LVESD)	LVESD at Baseline and at 6-months post Baseline	Change in the Left ventricular end-systolic dimension (LVESD) between Baseline and the value at the end of the randomization phase (6 months after Baseline) i.e. 6 months after vagus nerve stimulation in the THERAPY Arm. No Vagus nerve stimulation during that time window in the CONTROL Arm. The sign (- ) indicates a reduction in the LVESD. Minus means a reduction in LVESD. The change was calculated from two time points as the value at the later time point minus the value at the earlier time point (e.g., value at 6 months minus value at baseline).

Secondary Outcome Measures

Name	Time	Method
LVEF, Left Ventricular Ejection Fraction	LVEF at Baseline and at 6-months after Baseline	LVEF, left ventricular ejection fraction.
Exercise Capacity, Peak VO2	Measurements at Baseline and at 6-months after Baseline	Assessment of functional capacity (e.g., peak VO2) as measures related to patient heart failure status.
LVESV, Left Ventricular End Systolic Volume	At Baseline and at 6-months after Baseline	Measurements of LVESV, left ventricular end systolic volume at Baseline and 6 months after Baseline in the Control Arm and in the Therapy Arm

Trial Locations

Locations (21): King's College Hospital NHS Foundation Trust
🇬🇧
London, United Kingdom
Hospital Doce de Octubre
🇪🇸
Madrid, Spain
Catharina Ziekenhuis Eindhoven
🇳🇱
Eindhoven, Netherlands
The Heart Hospital, University College London Hospitals, NHS Foundation Trust
🇬🇧
London, England, United Kingdom
Universitätsmedizin Göttingen
🇩🇪
Göttingen, Germany
A. O. Dei Colli - Monaldi
🇮🇹
Napoli, Italy
Policlinico San Matteo
🇮🇹
Pavia, Italy
Azienda Ospedaliera Niguarda Cà Granda
🇮🇹
Milano, Italy
Clínica Universitaria de Navarra, Avenida Pio XII s/n
🇪🇸
Pamplona, Navarra, Spain
CHRU de Lille - Hôpital Cardiologique
🇫🇷
Lille, France
Nemocnice Na Homolce
🇨🇿
Prague, Czechia
Centre d'Investigation Clinique Pierre Drouin, CHU de Nancy
🇫🇷
Vandoeuvre les Nancy, Nancy, France
Immanuel Klinikum Bernau Herzzentrum Brandenburg
🇩🇪
Bernau, Brandenburg, Germany
Universitäres Herzzentrum GmbH, Universitätsklinikum Hamburg-Eppendorf
🇩🇪
Hamburg, Germany
UCL Bruxelles
🇧🇪
Brussels, Belgium
Universitätsklinikum Leipzig
🇩🇪
Leipzig, Germany
Hospital Clinic de Barcelona
🇪🇸
Barcelona, Spain
University Hospitals Bristol, NHS Foundation Trust
🇬🇧
Bristol, England, United Kingdom
UMC Utrecht
🇳🇱
Utrecht, Netherlands
Imperial College Healthcare NHS Trust, St. Mary's Hospital
🇬🇧
London, England, United Kingdom
Liverpool Heart and Chest Hospital, NHS Foundation Trust
🇬🇧
Liverpool, England, United Kingdom