MedPath

Antiarrhythmics or Ablation for Ventricular Tachycardia 2

Phase 4
Completed
Conditions
Ventricular Tachycardia (VT)
Interventions
Drug: Antiarrythmic Drug Therapy
Procedure: Catheter ablation
Registration Number
NCT02830360
Lead Sponsor
John Sapp
Brief Summary

A multicenter, randomized clinical trial to assess whether catheter ablation or antiarrhythmic drug therapy provides the most effective control of important clinical outcomes for patients with prior myocardial infarction and sustained monomorphic ventricular tachycardia (VT).

Detailed Description

Implantable Defibrillators (ICDs) reduce sudden death and can terminate some VT without shocks, but they don't prevent VT; the most appropriate strategy to suppress VT remains unknown. Two randomized clinical trials have suggested that catheter ablation can significantly reduce the incidence of subsequent VT in patients after an initial episode. Neither trial, however, compared catheter ablation to active antiarrhythmic drug therapy. Randomized trials of antiarrhythmic drug therapy have demonstrated that therapy with either sotalol or amiodarone can reduce recurrent VT. Both antiarrhythmic drug and ablation therapy suffer from imperfect efficacy and the potential for significant side-effects. No study has compared ablation to drug therapy for first-line treatment. The VANISH study which compared ablation to aggressive antiarrhythmic drug therapy for patients who have failed initial drug therapy was published in May 2016, and demonstrated that for patients with drug-refractory VT, catheter ablation was superior to escalation of antiarrhythmic drug therapy. Benefits were seen in the group which had VT despite amiodarone. Event rates were similar between amiodarone and sotalol for patients with VT occurring despite sotalol, who were randomized to either new initiation of amiodarone or catheter ablation. These results do not address the clinical question of the most appropriate first line therapy for suppression of VT in persons with prior myocardial infarction, an ICD and VT.

The trial hypothesis is: catheter ablation will, in comparison to antiarrhythmic drug therapy reduce the composite outcome of death at any time, appropriate ICD shock after 14 days, ventricular tachycardia storm after 14 days or treated sustained ventricular tachycardia below the detection rate of the ICD for patients with prior myocardial infarction and sustained monomorphic ventricular tachycardia.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
416
Inclusion Criteria
  • Prior Myocardial Infarction and

  • One of the following VT events while not being treated with amiodarone, sotalol, or another class I or class III antiarrhythmic drug) within the last 6 months:

    • Sustained monomorphic VT documented on 12-lead ECG or rhythm strip terminated by pharmacologic means or DC cardioversion
    • ≥3 episodes of VT treated with antitachycardia pacing (ATP), at least one of which was symptomatic
    • ≥ 5 episodes of VT treated with antitachycardia pacing (ATP) regardless of symptoms
    • ≥1 appropriate ICD shocks,
    • ≥3 VT episodes within 24 hours
Exclusion Criteria
  • Unable or unwilling to provide informed consent.
  • Active ischemia (acute thrombus diagnosed by coronary angiography, or dynamic ST segment changes demonstrated on ECG) or another reversible cause of VT (e.g. drug-induced arrhythmia), had recent acute coronary syndrome within 30 days, coronary revascularization (<90 days bypass surgery, <30 days percutaneous coronary intervention), or have CCS functional class IV angina. Note that biomarker level elevation alone after ventricular arrhythmias does not denote acute coronary syndrome or active ischemia.
  • Are ineligible to take the antiarrhythmic drug to which they would be assigned due to allergy, intolerance or contraindication
  • Are known to have protruding left ventricular thrombus or mechanical aortic and mitral valves
  • Have had a prior catheter ablation procedure for VT
  • Presenting arrhythmia: polymorphic VT or ventricular fibrillation (VF)
  • Are in renal failure (Creatinine clearance <15 mL/min), have NYHA Functional class IV heart failure, or a systemic illness likely to limit survival to <1 year
  • Have had recent ST elevation myocardial infarction or non-ST elevation MI (< 30 days); note that biomarker elevation alone after ventricular arrhythmias does not denote MI.
  • Are pregnant.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Antiarrhythmic Drug TherapyAntiarrythmic Drug TherapyPatients will be prescribed either oral amiodarone or sotalol daily (dosage and frequency to be determined based on patient's clinical presentation at the time of the qualifying arrhythmia).
VT catheter ablationCatheter ablationCatheter ablation of ventricular tachycardia
Primary Outcome Measures
NameTimeMethod
Appropriate ICD shock at least 14 days post randomization8 years (including pilot study data)

Time to first appropriate ICD shock after 14 days post randomization

VT storm at least 14 days post randomization8 years (including pilot study data)

Time to 3 or more episodes of VT within 24 hours

All-cause mortality8 years (including pilot study data)

Time to any death occurring at any time post randomization

Sustained VT requiring treatment at least 14 days post randomziation8 years (including pilot study data)

Time to any sustained VT greater below the detection rate of the ICD requiring cardioversion (electrical or chemical) or manual ICD therapy at least 14 days post randomization

Secondary Outcome Measures
NameTimeMethod
VT storm at any time or after 14 days8 years (including pilot study data)

3 or more episodes of VT occurring within 24 hours at any time post randomization; including incessant VT

Sustained VT not treated by ICD at any time or after 14 days8 years (including pilot study data)

any sustained VT greater than 30 seconds captured on a rhythm strip, monitor zone, holter monitor, or 12 lead ECG

Any ICD shock at any time or after 14 days6 years (including pilot study data)

Both appropriate and inappropriate shocks from the ICD at any time post randomization

Number of ICD shocks (all cause)8 years (including pilot study data)

the number of all shocks from any cause will be calculated

Number of VT storm events8 years (including pilot study data)

Total number of VT storms (3 episodes of VT within 24 hours)/ incessant VT will be calculated

Number of sustained VT events8 years (including pilot study data)

Total number of sustained VT (greater than 30 seconds)

All-cause mortality at any time8 years (including pilot study data)

Time to any death occurring at any time post randomization

Appropriate shocks at any time or after 14 days8 years (including pilot study data)

appropriate ICD shocks at any time post randomization

Time to sustained VT treated with appropriate any type of manual cardioversion after 14 days8 years (including pilot study data)

Any sustained VT greater than 30 seconds requiring manual cardioversion (ICD, external or pharmacologic)

Number of ICD appropriate therapy8 years (including pilot study data)

Total number of therapies which received appropriate ICD therapy

Hospital admission for cardiac causes8 years (including pilot study data)

Hospitalizations greater than 24 hours due to a cardiovascular cause.

Serious adverse events8 years (including pilot study data)

Serious events is any event which causes death, hospitalization, is life threatening and is directly related to the study treatment.

Quality of life - SF368 years (including pilot study data)

Will include responses from the Short Form 36

Quality of life - HADS8 years (including pilot study data)

Will include responses from the Hospital Anxiety and Depression Scale quesionnaire

Cost-effectiveness8 years (including pilot study data)

Quality adjusted life years (QALYs) will be derived from the case report forms and the questionnaires

Escalation and De-escalation of antiarrhythmic medication8 years (including pilot study data)

Any increase or decrease in the dosage of antiarrhythmic medication either due to inefficacy or side effects will be assessed.

Appropriate ICD ATP at any time or after 14 days8 years (including pilot study data)

any appropriate therapy delivered from the ICD at least 14 days post randomization

Number of Anti-tachycardia pacing (ATP)8 years (including pilot study data)

The total of all ATP delivered from the ICD will be calculated

Ablation procedural complications or antiarrhythmic drug adverse effects (this may require a separate substudy, depending on data complexity)8 years (including pilot study data)

Periprocedural complications and adverse drug reactions will be assessed

Quality of life - EQ5D8 years (including pilot study data))

Will include responses from the Euroquol 5D questionnaire

ICD Revision8 years (including pilot study data)

Surgical revisions to implanted defibrillators at any time

Inappropriate ICD shocks at any time or after 14 days8 years (including pilot study data)

all inappropriate shocks from the ICD at any time post randomization

Any ventricular arrhythmia event at any time or after 14 days (composite of appropriate ATP, appropriate shock, sustained VT not treated by ICD, external cardioversion, or pharmacologic cardioversion)8 years (including pilot study data)

All ventricular arrhythmias including a composite of: appropriate ATP, appropriate shock, sustained VT not treated by ICD, external cardioversion, or pharmacologic cardioversion), VT storm/incessant VT.

Side effects from anti-arrhythmic medication8 years (including pilot study data)

Any dose change or discontinuation of anti-arrhythmic medication due to abnormal blood tests (including kidney function, liver function, thyroid function) or any perceived side effects.

Number of ventricular arrhythmia events8 years (including pilot study data)

This is a composite of appropriate ATP, appropriate shock, sustained VT not treated by ICD, external cardioversion, or pharmacologic cardioversion, or VT storm/incessant VT. VT events which do not terminate despite exhausting ICD therapies will be considered incessant VT and included within the definition of VT storm.

Trial Locations

Locations (22)

Hartford General Hospital

🇺🇸

Hartford, Connecticut, United States

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

Foothills Hospital

🇨🇦

Calgary, Alberta, Canada

Interior Health Authority

🇨🇦

Kelowna, British Columbia, Canada

St. Paul's Hospital

🇨🇦

Vancouver, British Columbia, Canada

Royal Jubilee Hospital

🇨🇦

Victoria, British Columbia, Canada

Nova Scotia Health Authority

🇨🇦

Halifax, Nova Scotia, Canada

Hamilton Health Sciences Center

🇨🇦

Hamilton, Ontario, Canada

Queen's University Health Sciences Centre

🇨🇦

Kingston, Ontario, Canada

St. Mary's Hospital

🇨🇦

Kitchener, Ontario, Canada

London Health Sciences Centre

🇨🇦

London, Ontario, Canada

University of Ottawa Heart Institute

🇨🇦

Ottawa, Ontario, Canada

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Montreal Heart Institute

🇨🇦

Montreal, Quebec, Canada

McGill University Health Center

🇨🇦

Montreal, Quebec, Canada

Centre Hospitalier de l'Universitaire de Montreal

🇨🇦

Montréal, Quebec, Canada

Sacre-Coeur Hospital

🇨🇦

Montréal, Quebec, Canada

Institut Universitaire de cardiologie et pneumologie de Quebec - Laval University Hosptial

🇨🇦

Quebec CIty, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke

🇨🇦

Sherbrooke, Quebec, Canada

Hopitaux de Bordeaux

🇫🇷

Bordeaux, Acquitaine, France

CHU - University Hospital Nancy

🇫🇷

Nancy, Meurthe-et-Moselle, France

Vanderbilt University Hospital

🇺🇸

Nashville, Tennessee, United States

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