Clinical trial NCT02830360: Antiarrhythmics or Ablation for Ventricular Tachycardia 2
Official title: Ventricular Tachycardia Antiarrhythmics or AblatioN In Structural Heart Disease 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ventricular Tachycardia (VT)
Keywords: Antiarrhythmic drug therapy
VT Catheter ablation
ICD Therapy
Ischemic Heart Disease
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Canada
name: Abbott Medical Devices
name: Biosense Webster, Inc.
name: Ottawa Heart Institute Research Corporation
name: Canadian Institutes of Health Research (CIHR)
name: Cardiac Arrhythmia Network of Canada
name: Abbott
name: Nova Scotia Health Authority
First posted: 2016-07-12
Enrollment: 416
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: All-cause mortality
timeFrame: 8 years (including pilot study data)
measure: Appropriate ICD shock at least 14 days post randomization
timeFrame: 8 years (including pilot study data)
measure: VT storm at least 14 days post randomization
timeFrame: 8 years (including pilot study data)
measure: Sustained VT requiring treatment at least 14 days post randomziation
timeFrame: 8 years (including pilot study data)
Secondary outcomes:
measure: All-cause mortality at any time
timeFrame: 8 years (including pilot study data)
measure: Appropriate ICD ATP at any time or after 14 days
timeFrame: 8 years (including pilot study data)
measure: Appropriate shocks at any time or after 14 days
timeFrame: 8 years (including pilot study data)
measure: VT storm at any time or after 14 days
timeFrame: 8 years (including pilot study data)
measure: Sustained VT not treated by ICD at any time or after 14 days
timeFrame: 8 years (including pilot study data)
measure: Time to sustained VT treated with appropriate any type of manual cardioversion after 14 days
timeFrame: 8 years (including pilot study data)
measure: Inappropriate ICD shocks at any time or after 14 days
timeFrame: 8 years (including pilot study data)
measure: Any ICD shock at any time or after 14 days
timeFrame: 6 years (including pilot study data)
measure: 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)
timeFrame: 8 years (including pilot study data)
measure: Number of ICD shocks (all cause)
timeFrame: 8 years (including pilot study data)
measure: Number of Anti-tachycardia pacing (ATP)
timeFrame: 8 years (including pilot study data)
measure: Number of ICD appropriate therapy
timeFrame: 8 years (including pilot study data)
measure: Number of VT storm events
timeFrame: 8 years (including pilot study data)
measure: Number of sustained VT events
timeFrame: 8 years (including pilot study data)
measure: Number of ventricular arrhythmia events
timeFrame: 8 years (including pilot study data)
measure: Hospital admission for cardiac causes
timeFrame: 8 years (including pilot study data)
measure: Ablation procedural complications or antiarrhythmic drug adverse effects (this may require a separate substudy, depending on data complexity)
timeFrame: 8 years (including pilot study data)
measure: Serious adverse events
timeFrame: 8 years (including pilot study data)
measure: Side effects from anti-arrhythmic medication
timeFrame: 8 years (including pilot study data)
measure: Quality of life - SF36
timeFrame: 8 years (including pilot study data)
measure: Quality of life - EQ5D
timeFrame: 8 years (including pilot study data))
measure: Quality of life - HADS
timeFrame: 8 years (including pilot study data)
measure: Cost-effectiveness
timeFrame: 8 years (including pilot study data)
measure: Escalation and De-escalation of antiarrhythmic medication
timeFrame: 8 years (including pilot study data)
measure: ICD Revision
timeFrame: 8 years (including pilot study data)
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford General Hospital
state: Connecticut
city: Nashville
country: United States
facility: Vanderbilt University Hospital
state: Tennessee
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Kelowna
country: Canada
facility: Interior Health Authority
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Center
state: Ontario
city: Kingston
country: Canada
facility: Queen's University Health Sciences Centre
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universitaire de Montreal
state: Quebec
city: Montréal
country: Canada
facility: Sacre-Coeur Hospital
state: Quebec
city: Quebec CIty
country: Canada
facility: Institut Universitaire de cardiologie et pneumologie de Quebec - Laval University Hosptial
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Bordeaux
country: France
facility: Hopitaux de Bordeaux
state: Acquitaine
city: Nancy
country: France
facility: CHU - University Hospital Nancy
state: Meurthe-et-Moselle
Study officials:
affiliation: Nova Scotia Health Authority
name: John L Sapp, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Nova Scotia Health Authoriry
name: Ratika Parkash, MD MSc FRCPC
role: STUDY_DIRECTOR
affiliation: London Health Sciences Centre
name: Anthony L Tang, MD FRCPC
role: STUDY_DIRECTOR
affiliation: Ottawa Heart Institute Research Corporation
name: George A Wells, BSc MSc PhD
role: STUDY_DIRECTOR
affiliation: Brigham and Women's Hospital
name: William G Stevenson, MD
role: STUDY_DIRECTOR
affiliation: Population Health Research Institute, McMaster University
name: Jeff Healey, MD FRCPC
role: STUDY_DIRECTOR
References:
citation: Kheiri B, Barbarawi M, Zayed Y, Hicks M, Osman M, Rashdan L, Kyi HH, Bachuwa G, Hassan M, Stecker EC, Nazer B, Bhatt DL. Antiarrhythmic Drugs or Catheter Ablation in the Management of Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Circ Arrhythm Electrophysiol. 2019 Nov;12(11):e007600. doi: 10.1161/CIRCEP.119.007600. Epub 2019 Nov 8.