Cardiac Denervation Surgery for Prevention of Ventricular Tacharrhythmias (PREVENT VT)

This study is not yet open for participant recruitment.
Verified January 2014 by University of California, Los Angeles
Sponsor:
Collaborators:
Mayo Clinic
University of Kansas
Minneapolis VA Health Care System, Minneapolis, Minnesota
Texas Cardiac Arrhythmia Research Foundation
Washington University School of Medicine
Intermountain Health Medical Center, Salt Lake City, Utah
Johns Hopkins University
University of Pennsylvania
Texas Heart Institute
Information provided by (Responsible Party):
Marmar Vaseghi, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01013714
First received: November 13, 2009
Last updated: January 5, 2014
Last verified: January 2014
  Purpose

The purpose of this research study is to examine the effect of cardiac denervation surgery, otherwise known as bilateral cervicothoracic sympathectomy (CTS), on life threatening abnormal heart rhythms called ventricular tachycardia or ventricular fibrillation that can lead to sudden cardiac death.

Subjects will be asked to participate in this research trial if they have had recurrent ventricular tachycardia (at least one ICD shock for ventricular tachycardia) and have undergone at least one catheter ablation procedure or have ventricular tachycardia or fibrillation that is not ablatable. The goal of this study is to determine whether bilateral cervicothoracic sympathectomy can prevent these abnormal heart rhythms from occurring and therefore, prevent, ICD shocks, which are not only painful, but have been shown to reduce quality of life and/or lead to depression, particularly in the period immediately after the shock.


Condition Intervention Phase
Sudden Cardiac Death
Ventricular Tachycardia
Ventricular Fibrillation
Cardiomyopathy
Procedure: Bilateral cervicothoracic sympathectomy plux maximum medical therapy
Drug: Maximum medical therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prophylactic Bilateral Cervicothoracic Sympathectomy for Prevention of Ventricular Tachyarrhythmias

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Survival free from any appropriate ICD shock 1 month after sympathectomy procedure. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The primary end point: to compare the event free survival from ICD shocks in patients with bilateral CTS and medical therapy compared to medical therapy alone.


Secondary Outcome Measures:
  • Freedom from any appropriate ICD therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Secondary end-point: to compare the number of ICD therapies in patients with bilateral CTS and medical therapy to medical therapy alone.

  • Freedom from ICD shocks [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Secondary end-point: to compare the burden of ICD shocks in patients with bilateral CTS and medical therapy to those on medical therapy alone.

  • Primary and serious adverse events [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Secondary end-point: to assess the occurrence of primary and serious adverse events in patients with bilateral CTS and medical therapy compared to those on medical therapy alone

  • Cardiac mechanical and electrical indices of heart failure and sudden death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the effect of bilateral CTS and medical therapy vs. medical therapy alone on cardiac mechanical and electrical indices including EF and Tp-Te interval and QT/QTc interval

  • Quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the effects of bilateral CTS and medical therapy vs. medical therapy alone on quality of life.

  • Cardiac Biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the effects of bilateral CTS on biomarkers including BNP, galectin-3, troponin, and high sensitivity C-reactive protein.


Estimated Enrollment: 322
Study Start Date: July 2014
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sympathectomy + medical therapy + ICD

Bilateral cervicothoracic sympathectomy will be performed in patients randomized to the Active Therapy Arm via endoscopic procedure (VATS) with removal of the lower half of the bilateral cervico-thoracic (stellate) ganglia and T2-T4 ganglia.

All patients meeting the inclusion criteria of this study will have undergone or will undergo an ICD placement based on ACC/AHA criteria.

All participants will have had at least one ICD shock despite having a catheter ablation of VT performed prior to enrollment.

If patient has a recurrent ICD shock while enrolled in the study, repeat VT ablation procedure, as indicated, can be performed.

Follow-up Visits

  • Surgical follow up will occur at 2-4 weeks after discharge in the sympathectomy group.
  • All patients will be followed up every 6 months up to 24 months at the ICD clinic.
  • Information regarding ICD therapy and arrhythmias will be obtained from ICD interrogations at these follow ups.
Procedure: Bilateral cervicothoracic sympathectomy plux maximum medical therapy
Bilateral cervicothoracic sympathectomy which involves endoscopic removal of the lower one third to one half of the stellate ganglia together with the thoracic ganglia of T2 - T4 provides adequate cardiac denervation with no or minimal Horner's syndrome in long QT syndrome and recurrent angina. Though this procedure has been traditionally performed under general anesthesia most commonly using a supraclavicular approach, endoscopic techniques are now available, reducing both the duration and invasiveness of the procedure and hospitalization. Video-assisted thoracoscopic sympathectomy provides a minimally invasive endoscopic approach to this procedure that is safe and effective. Furthermore, the procedure can be completed in less than 45 minutes per side.
Placebo Comparator: Standard medical therapy, ICD

Patients assigned to this arm will not undergo denervation therapy (CTS). All patients meeting inclusion criteria of this study and randomized to the placebo arm will have undergone or will undergo an ICD based on ACC/AHA criteria.

If patient has a recurrent ICD shock while enrolled, a repeat VT ablation procedure as clinically indicated, can be performed.

  • Single or dual chamber device
  • ICD Programming to minimize ventricular pacing unless biventricular pacing indicated.
  • VF zone greater than 200 BPM
  • Bradycardia at 40 BPM with hysteresis, unless biventricular pacing indicated.
  • ATP: Burst pacing for monomorphic VT x 3.
  • VT zone programmed to 10 beats faster than clinical VT

Follow-up Visits

• All patients: 2-4 weeks post randomization for adjustment of anti-arrhythmic and other medical therapy, then every 6 months up to 24 months Information regarding ICD therapy and arrhythmias will be obtained from ICD interrogations.

Drug: Maximum medical therapy
Patients assigned to this arm will receive ACC/AHA guideline recommended therapies for heart failure only and will undergo/will have already undergone ICD placement as indicated for their heart failure. Furthermore, they will be considered for catheter ablation of their arrhythmia and will undergo catheter ablation of their ventricular arrhythmias prior to randomization.

Detailed Description:

The purpose of this research study is to examine the effect of a procedure called bilateral cervicothoracic sympathectomy which involves removal of part of the cervical stellate ganglia and thoracic ganglia of level 2 to 4. These ganglia house the left and right sided nerves that feed the heart and have been implicated in the occurrence of fast abnormal rhythms that cause defibrillator shocks and sudden death. Stimulation of these nerves has been shown to increase the incidence of sudden death and fast abnormal heart rhythms that lead to internal defibrillator shocks called ventricular tachycardia/ventricular fibrillation. Removal of the ganglia of these nerves in animal and human studies has been shown to decrease the incidence of life threatening abnormal rhythms and sudden death. The purpose of this study is to examine whether this procedure along with current maximum medical therapy can reduce the incidence of these life threatening abnormal rhythms as compared to an maximum medical therapy alone.

We are inviting patients to participate in this clinical trial who have undergone at least one catheter ablation procedure for ventricular tachycardia but have continued to experience recurrent arrhythmias (ICD shocks) or who have a type of ventricular tachycardia or fibrillation that can not be treated with catheter ablation procedures. You maybe randomized to receive the procedure plus maximum medical therapy or maximum medical therapy alone. The procedure involves removal of part of the bilateral ganglia of the nerves that feed the heart. This procedure takes less than 45 minutes on each side and can be performed endoscopically.

We are asking 322 individuals (approximate age range 18-80 years) who continue to experience ICD shocks to participate in this research trial but only half these individual will be randomized under the bilateral cervicothoracic sympathectomy.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Drug refractory (including beta-blockers and one anti-arrhythmic or has documented intolerance to or toxicity from beta-blockers and at least one anti-arrhythmic) ventricular tachy-arrhythmias leading to an ICD shock after at least one catheter ablation procedure for VT, OR drug refractory ventricular tachy-arrhythmias leading to an ICD shock that are not amenable to or clinically appropriate for catheter ablation procedures. Clinically appropriate is defined as those patients with MMVT. Those with PMVT or idiopathic VF are not required to have had previous ablation. ICD shock needs to have occurred in the 6 months prior to randomization. Epicardial mapping is encouraged, but not required, for non-ischemic cardiomyopathy patients.
  • Qualifying episode must be sustained VT and require an ICD shock.
  • If ischemic cardiomyopathy, myocardial infarction occurred more than one month before enrollment.
  • ICD implantation
  • Age greater than 18 years old.
  • Able and willing to comply with all pre- and follow-up testing and requirements.
  • Signed informed consent form.

Exclusion Criteria:

  • Active ongoing cardiac ischemia as assessed by: ECG, cardiac enzymes, symptoms, coronary angiography with evidence of significant epicardial coronary stenosis (>70%), or stress testing. (Note: positive troponin assay due to ICD shocks is not an exclusion criterion).
  • Revascularization in the past 90 days.
  • Incessant VT: defined as sustained VT over >3 hour period despite anti-arrhythmic therapy and catheter ablation.
  • Any medical or non-medical condition likely to prevent completion of trial.
  • Contraindication to sympathectomy (i.e. unlikely to tolerate general anesthesia, single-lung ventilation, severe pulmonary disease, or severe pulmonary hypertension) or previous cardiac sympathectomy procedure.
  • Left ventricular assist device or status post orthotopic heart transplantation
  • Other disease processes likely to limit survival to less than 12 months.
  • Severe thrombocytopenia (platelets < 50,000) or coagulopathy (INR > 2.0) that is not due to medications or a reversible cause.
  • Women who are pregnant (as evidenced by pregnancy test if pre-menopausal).
  • Unable or unwilling to comply with protocol requirements.
  • Slow VT, rate < 120 bpm.
  • Acute congestive heart failure exacerbation.
  • Known channelopathy such as long QT syndrome and catecholaminergic polymorphic VT.
  • Inability to give informed consent.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01013714

Contacts
Contact: Kalyanam Shivkumar, MD, PhD 310-206-2235 kshivkumar@mednet.ucla.edu
Contact: Marmar Vaseghi, MD 310-206-2235 mvaseghi@mednet.ucla.edu

Locations
United States, California
UCLA Not yet recruiting
Los Angeles, California, United States, 90065
Contact: Michelle Betwarda, M.S.    310-206-2235    mbetwarda@mednet.ucla.edu   
Contact: Marmar Vaseghi, MD    310-206-2235    mvaseghi@mednet.ucla.edu   
Principal Investigator: Kalyanam Shivkumar, MD, PhD         
Sub-Investigator: Marmar Vaseghi, MD         
Sponsors and Collaborators
University of California, Los Angeles
Mayo Clinic
University of Kansas
Minneapolis VA Health Care System, Minneapolis, Minnesota
Texas Cardiac Arrhythmia Research Foundation
Washington University School of Medicine
Intermountain Health Medical Center, Salt Lake City, Utah
Johns Hopkins University
University of Pennsylvania
Texas Heart Institute
Investigators
Principal Investigator: Kalyanam Shivkumar, MD, PhD University of California Los Angeles Cardiac Arrhythmia Center
Principal Investigator: Marmar Vaseghi, MD MS University of California, Los Angeles
  More Information

Publications:

Responsible Party: Marmar Vaseghi, Assistant Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01013714     History of Changes
Other Study ID Numbers: UCLA09-07-100-01
Study First Received: November 13, 2009
Last Updated: January 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Sudden cardiac death
Ventricular tachycardia
Ventricular fibrillation
Cardiomyopathy
Internal cardiac defibrillator shocks
Internal cardiac defibrillator therapies

Additional relevant MeSH terms:
Tachycardia, Ventricular
Death
Tachycardia
Ventricular Fibrillation
Death, Sudden, Cardiac
Cardiomyopathies
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Heart Arrest
Death, Sudden

ClinicalTrials.gov processed this record on April 16, 2014