Antiarrhythmics or Ablation for Ventricular Tachycardia 2

Ventricular Tachycardia (VT) Clinical Trial

— VANISH2  

Official title:

Ventricular Tachycardia Antiarrhythmics or AblatioN In Structural Heart Disease 2

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02830360
• Other study ID #: SAPP004
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2023
• Source: Nova Scotia Health Authority
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 416
• Est. completion date: December 31, 2024
• Est. primary completion date: June 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Tachycardia
• Tachycardia, Ventricular
• Ventricular Tachycardia (VT)

Intervention

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.)

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.

Locations

Country	Name	City	State
Canada	Foothills Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Center	Hamilton	Ontario
Canada	Interior Health Authority	Kelowna	British Columbia
Canada	Queen's University Health Sciences Centre	Kingston	Ontario
Canada	St. Mary's Hospital	Kitchener	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	McGill University Health Center	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Centre Hospitalier de l'Universitaire de Montreal	Montréal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut Universitaire de cardiologie et pneumologie de Quebec - Laval University Hosptial	Quebec CIty	Quebec
Canada	Centre Hospitalier Univesitaire de Sherbrooke	Sherbrooke	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Fraser Health Authority - Royal Columbian Hospital	Vancouver	British Columbia
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Royal Jubilee Hospital	Victoria	British Columbia
France	Hopitaux de Bordeaux	Bordeaux	Acquitaine
France	CHU - University Hospital Nancy	Nancy	Meurthe-et-Moselle
United States	Vanderbilt University Hospital	Nashville	Tennessee

Sponsors (9)

Lead Sponsor	Collaborator
John Sapp	Abbott, Abbott Medical Devices, Biosense Webster, Inc., Canadian Institutes of Health Research (CIHR), Cardiac Arrhythmia Network of Canada, Heart and Stroke Foundation of Canada, Nova Scotia Health Authority, Ottawa Heart Institute Research Corporation

Countries where clinical trial is conducted

United States,  Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality	Time to any death occurring at any time post randomization	8 years (including pilot study data)
Primary	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)
Primary	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)
Primary	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	All-cause mortality at any time	Time to any death occurring at any time post randomization	8 years (including pilot study data)
Secondary	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)
Secondary	Appropriate shocks	appropriate ICD shocks at any time post randomization	8 years (including pilot study data)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Number of ICD shocks (all cause)	the number of all shocks from any cause will be calculated	8 years (including pilot study data)
Secondary	Number of Anti-tachycardia pacing (ATP)	The total of all ATP delivered from the ICD will be calculated	8 years (including pilot study data)
Secondary	Number of ICD appropriate therapy	Total number of therapies which received appropriate ICD therapy	8 years (including pilot study data)
Secondary	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)
Secondary	Number of sustained VT events	Total number of sustained VT (greater than 30 seconds)	8 years (including pilot study data)
Secondary	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)
Secondary	Hospital admission for cardiac causes	Hospitalizations greater than 24 hours due to a cardiovascular cause.	8 years (including pilot study data)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Quality of life - SF36	Will include responses from the Short Form 36	8 years (including pilot study data)
Secondary	Quality of life - EQ5D	Will include responses from the Euroquol 5D questionnaire	8 years (including pilot study data))
Secondary	Quality of life - HADS	Will include responses from the Hospital Anxiety and Depression Scale quesionnaire	8 years (including pilot study data)
Secondary	Cost-effectiveness	Quality adjusted life years (QALYs) will be derived from the case report forms and the questionnaires	8 years (including pilot study data)
Secondary	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)