Antiarrhythmics or Ablation for Ventricular Tachycardia 2

Study Overview
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Brief Summary
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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
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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.

Official Title
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Ventricular Tachycardia Antiarrhythmics or AblatioN In Structural Heart Disease 2

Conditions
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Ventricular Tachycardia (VT)

Intervention / Treatment
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* Drug: Antiarrythmic Drug Therapy
* Procedure: Catheter ablation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VT catheter ablation<br>Catheter ablation of ventricular tachycardia | Procedure: Catheter ablation<br>* 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.<br>* Other names: VT ablation;|
| Active Comparator: Antiarrhythmic Drug Therapy<br>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<br>* 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.)<br>* Other names: Amiodarone (Cordarone) or Sotalol (Sotacor);|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiarrhythmic drug therapy, VT Catheter ablation, ICD Therapy, Ischemic Heart Disease