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

NCT01385176 | Active Not Recruiting Results DMC

• 1 other identifier: NECTAR-1109
• Study Type: interventional
• Target: 118
• Locations: 8 countries
• Sites: 21

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.

Conditions

Heart Failure; Congestive Heart Failure

Keywords

Heart failure; Congestive heart failure; New York Heart Association Class II-III; Vagal therapy; Vagal nerve stimulation

Outcome Measures

Primary Outcomes (2)

• Change in Left Ventricular End-systolic Dimension (LVESD)

  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).

  LVESD at Baseline and at 6-months post Baseline

• Percentage of Surviving Participants

  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.

  18-months

Secondary Outcomes (3)

• LVEF, Left Ventricular Ejection Fraction

  LVEF at Baseline and at 6-months after Baseline

• Exercise Capacity, Peak VO2

  Measurements at Baseline and at 6-months after Baseline

• LVESV, Left Ventricular End Systolic Volume

  At Baseline and at 6-months after Baseline

Study Arms (2)

Therapy

EXPERIMENTAL

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.

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

Control

SHAM COMPARATOR

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.

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

Interventions

Implant of investigational device system DEVICE

Vagus nerve stimulation lead was wrapped around the right cervical vagus nerve and then connected to a stimulator permanently implanted in the right pectoral region.

Control; Therapy

Titration during the randomization phase PROCEDURE

Amplitude of the chronically delivered vagus nerve stimulation in the experimental arm was adjusted to the highest tolerable by patient value. No chronically delivered vagus nerve stimulation in the control arm during the randomization phase.

Therapy

Titration after the randomization phase PROCEDURE

Amplitude of the chronically delivered vagus nerve stimulation was adjusted to the highest tolerable by patient value in all patients in both arms of the study.

Control; Therapy

Blood Draw DIAGNOSTIC_TEST

Blood draw before implant and 6 months after implant at the end of the randomization phase.

Control; Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Scientific Corporation: lead

Study Sites (21)

UCL Bruxelles

Brussels, 1200, Belgium

Location

Nemocnice Na Homolce

Prague, 15030, Czechia

Location

Centre d'Investigation Clinique Pierre Drouin, CHU de Nancy

Vandœuvre-lès-Nancy, Nancy, 54500, France

Location

CHRU de Lille - Hôpital Cardiologique

Lille, 59037, France

Location

Immanuel Klinikum Bernau Herzzentrum Brandenburg

Bernau bei Berlin, Brandenburg, 16321, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Universitäres Herzzentrum GmbH, Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Azienda Ospedaliera Niguarda Cà Granda

Milan, 20162, Italy

Location

A. O. Dei Colli - Monaldi

Naples, 80131, Italy

Location

Policlinico San Matteo

Pavia, 27100, Italy

Location

Catharina Ziekenhuis Eindhoven

Eindhoven, 5623EJ, Netherlands

Location

UMC Utrecht

Utrecht, 3584CX, Netherlands

Location

Clínica Universitaria de Navarra, Avenida Pio XII s/n

Pamplona, Navarre, 31008, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Doce de Octubre

Madrid, 28041, Spain

Location

University Hospitals Bristol, NHS Foundation Trust

Bristol, England, BS2 8HW, United Kingdom

Location

Liverpool Heart and Chest Hospital, NHS Foundation Trust

Liverpool, England, L14 3PD, United Kingdom

Location

The Heart Hospital, University College London Hospitals, NHS Foundation Trust

London, England, W1G 8PH, United Kingdom

Location

Imperial College Healthcare NHS Trust, St. Mary's Hospital

London, England, W2 1NY, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (3)

• De Ferrari GM, Tuinenburg AE, Ruble S, Brugada J, Klein H, Butter C, Wright DJ, Schubert B, Solomon S, Meyer S, Stein K, Ramuzat A, Zannad F. Rationale and study design of the NEuroCardiac TherApy foR Heart Failure Study: NECTAR-HF. Eur J Heart Fail. 2014 Jun;16(6):692-9. doi: 10.1002/ejhf.80. Epub 2014 May 20.

  PMID: 24846173 BACKGROUND

• Zannad F, De Ferrari GM, Tuinenburg AE, Wright D, Brugada J, Butter C, Klein H, Stolen C, Meyer S, Stein KM, Ramuzat A, Schubert B, Daum D, Neuzil P, Botman C, Castel MA, D'Onofrio A, Solomon SD, Wold N, Ruble SB. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J. 2015 Feb 14;36(7):425-33. doi: 10.1093/eurheartj/ehu345. Epub 2014 Aug 31.

  PMID: 25176942 RESULT

• De Ferrari GM, Stolen C, Tuinenburg AE, Wright DJ, Brugada J, Butter C, Klein H, Neuzil P, Botman C, Castel MA, D'Onofrio A, de Borst GJ, Solomon S, Stein KM, Schubert B, Stalsberg K, Wold N, Ruble S, Zannad F. Long-term vagal stimulation for heart failure: Eighteen month results from the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) trial. Int J Cardiol. 2017 Oct 1;244:229-234. doi: 10.1016/j.ijcard.2017.06.036. Epub 2017 Jun 10.

  PMID: 28663046 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

Inappropriate patient selection may have also contributed to the neutral findings. In the present study, therapy patients experienced side effects (e.g. neck pain, coughing), which limited programming to low stimulation amplitudes.

Results Point of Contact

• Title: Principal Investigator of the Study, Prof. Faiez Zannad
• Organization: Institut Lorrain du Coeur et des Vaisseaux, CHU de Nancy, France

f.zannad@chu-nancy.fr

+33 3 83 15 73 22

Study Officials

• Faiez Zannad, M.D.

  Centre d'Investigation Clinique (CIC), Batiment Louis Mathieu, CHU de Nancy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients were randomized in a 2:1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LVend systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers.

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: June 30, 2011
• Study Start: September 21, 2011
• Primary Completion: May 1, 2014
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 29, 2026
• Results First Posted: January 6, 2020

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); GB (5); DE (4); CZ (1); FR (2); BE (1); IT (3); NL (2)