Antiarrhythmics or Ablation for Ventricular Tachycardia 2 (VANISH2)

Ventricular Tachycardia Antiarrhythmics or AblatioN In Structural Heart Disease 2

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Ventricular Tachycardia (VT)
• Intervention / Treatment: Procedure: Catheter ablation; Drug: Antiarrythmic Drug Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2W 1S7
      • Foothills Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1T2
      • Interior Health Authority
    • Vancouver, British Columbia, Canada, V6E 1M7
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V3T OH1
      • Fraser Health Authority - Royal Columbian Hospital
    • Victoria, British Columbia, Canada, V8R 1J8
      • Royal Jubilee Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8L 8E7
      • Hamilton Health Sciences Center
    • Kingston, Ontario, Canada, K7L 2V7
      • Queen's University Health Sciences Centre
    • Kitchener, Ontario, Canada, N2M 1B2
      • St. Mary's Hospital
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Montreal, Quebec, Canada, H3H 1A4
      • McGill University Health center
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universitaire de Montreal
    • Quebec CIty, Quebec, Canada, G1V 4G5
      • Institut Universitaire de cardiologie et pneumologie de Quebec - Laval University Hosptial
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Univesitaire de Sherbrooke
• France
  • Acquitaine
    • Bordeaux, Acquitaine, France, 33604
      • Hopitaux de Bordeaux
  • Meurthe-et-Moselle
    • Nancy, Meurthe-et-Moselle, France, 54511
      • CHU - University Hospital Nancy
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VT catheter ablation; Catheter ablation of ventricular tachycardia	Procedure: Catheter ablation; Intracardiac electrode catheters are placed via central vasculature to identify myocardial scar, and surviving conduction channels within the scar which form the substrate for ventricular tachycardia. Radiofrequency energy is applied to these sites, interrupting the VT circuits.; Other Names: VT ablation
Active Comparator: Antiarrhythmic Drug Therapy; Patients 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).	Drug: Antiarrythmic Drug Therapy; Patients will be prescribed antiarrhythmic drugs (either amiodarone or sotalol based on specific clinical presentation, including medical history, functional class, ejection fraction, and renal function.); Other Names: Amiodarone (Cordarone) or Sotalol (Sotacor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Time to any death occurring at any time post randomization	8 years (including pilot study data)
Appropriate ICD shock at least 14 days post randomization	Time to first appropriate ICD shock after 14 days post randomization	8 years (including pilot study data)
VT storm at least 14 days post randomization	Time to 3 or more episodes of VT within 24 hours	8 years (including pilot study data)
Sustained VT requiring treatment at least 14 days post randomziation	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	8 years (including pilot study data)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at any time	Time to any death occurring at any time post randomization	8 years (including pilot study data)
Appropriate ICD ATP at any time or after 14 days	any appropriate therapy delivered from the ICD at least 14 days post randomization	8 years (including pilot study data)
Appropriate shocks	appropriate ICD shocks at any time post randomization	8 years (including pilot study data)
VT storm at any time or after 14 days	3 or more episodes of VT occurring within 24 hours at any time post randomization; including incessant VT	8 years (including pilot study data)
Sustained VT not treated by ICD at any time or after 14 days	any sustained VT greater than 30 seconds captured on a rhythm strip, monitor zone, holter monitor, or 12 lead ECG	8 years (including pilot study data)
Time to sustained VT treated with appropriate any type of manual cardioversion after 14 days	Any sustained VT greater than 30 seconds requiring manual cardioversion (ICD, external or pharmacologic)	8 years (including pilot study data)
Inappropriate ICD shocks at any time or after 14 days	all inappropriate shocks from the ICD at any time post randomization	8 years (including pilot study data)
Any ICD shock at any time or after 14 days	Both appropriate and inappropriate shocks from the ICD at any time post randomization	6 years (including pilot study data)
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)	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.	8 years (including pilot study data)
Number of ICD shocks (all cause)	the number of all shocks from any cause will be calculated	8 years (including pilot study data)
Number of Anti-tachycardia pacing (ATP)	The total of all ATP delivered from the ICD will be calculated	8 years (including pilot study data)
Number of ICD appropriate therapy	Total number of therapies which received appropriate ICD therapy	8 years (including pilot study data)
Number of VT storm events	Total number of VT storms (3 episodes of VT within 24 hours)/ incessant VT will be calculated	8 years (including pilot study data)
Number of sustained VT events	Total number of sustained VT (greater than 30 seconds)	8 years (including pilot study data)
Number of ventricular arrhythmia events	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.	8 years (including pilot study data)
Hospital admission for cardiac causes	Hospitalizations greater than 24 hours due to a cardiovascular cause.	8 years (including pilot study data)
Ablation procedural complications or antiarrhythmic drug adverse effects (this may require a separate substudy, depending on data complexity)	Periprocedural complications and adverse drug reactions will be assessed	8 years (including pilot study data)
Time to any serious adverse events	Serious events is any event which causes death, hospitalization, is life threatening and is directly related to the study treatment.	8 years (including pilot study data)
Side effects from anti-arrhythmic medication	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.	8 years (including pilot study data)
Quality of life - SF36	Will include responses from the Short Form 36	8 years (including pilot study data)
Quality of life - EQ5D	Will include responses from the Euroquol 5D questionnaire	8 years (including pilot study data))
Quality of life - HADS	Will include responses from the Hospital Anxiety and Depression Scale quesionnaire	8 years (including pilot study data)
Cost-effectiveness	Quality adjusted life years (QALYs) will be derived from the case report forms and the questionnaires	8 years (including pilot study data)
Escalation and De-escalation of antiarrhythmic medication	Any increase or decrease in the dosage of antiarrhythmic medication either due to inefficacy or side effects will be assessed.	8 years (including pilot study data)

Collaborators and Investigators

• Sponsor: John Sapp
• Collaborators: Canadian Institutes of Health Research (CIHR); Nova Scotia Health Authority; Abbott Medical Devices; Abbott; Ottawa Heart Institute Research Corporation; Biosense Webster, Inc.; Heart and Stroke Foundation of Canada; Cardiac Arrhythmia Network of Canada
• Investigators: Study Director: Ratika Parkash, MD MSc FRCPC, Nova Scotia Health Authoriry; Study Director: Anthony L Tang, MD FRCPC, London Health Sciences Centre; Study Director: George A Wells, BSc MSc PhD, Ottawa Heart Institute Research Corporation; Study Director: Jeff Healey, MD FRCPC, Population Health Research Institute, McMaster University; Principal Investigator: John L Sapp, MD FRCPC, Nova Scotia Health Authority; Study Director: William G Stevenson, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Estimated): June 6, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (Estimated): July 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Ischemic Heart Disease; ICD Therapy; Antiarrhythmic drug therapy; VT Catheter ablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Tachycardia; Tachycardia, Ventricular; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Sympatholytics; Potassium Channel Blockers; Amiodarone; Sotalol
• Other Study ID Numbers: SAPP004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO