Ventricular Tachycardia (VT) Ablation or Escalated Drug Therapy (VANISH)

Ventricular Tachycardia Ablation or Escalated aNtiarrhythmic Drugs in ISchemic Heart Disease

This study will compare aggressive antiarrhythmic therapy to catheter ablation for ventricular tachycardia in patients who have suffered prior myocardial infarction. The purpose of this study is to evaluate the optimal management of patients presenting with recurrent VT and receiving ICD therapy in spite of first-line antiarrhythmic drug therapy. The hypothesis is catheter ablation is superior to aggressive antiarrhythmic drug therapy for recurrent VT.

Study Overview

• Status: Completed
• Conditions: Recurrent Ventricular Tachycardia
• Intervention / Treatment: Procedure: Catheter Ablation; Drug: Escalated Antiarrhythmic Therapy

Detailed Description

This is a multicentre, parallel group, two arm, unblinded, randomized clinical trial to compare two management strategies for patients with ischemic heart disease and recurrent ICD therapy despite at least one antiarrhythmic drug. The primary endpoint will be a composite of appropriate ICD shocks or death.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QEII Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior Myocardial Infarction
• An implantable defibrillator

• One of the following VT events (within the past 3 months):

  • greater than or equal to 3 episodes of symptomatic VT treated with ATP
  • greater than or equal to 1 appropriate ICD shock
  • greater than or equal to 3 VT episodes within 24 hours
  • sustained VT below detection rate of the ICD documented by ECG

• "Failed" first-line antiarrhythmic drug therapy as defined by one of:

  • Appropriate ICD therapy or sustained VT occurred while patient was taking amiodarone (stable dose >/= 2 weeks)
  • Appropriate ICD therapy or sustained VT occurred on another antiarrhythmic drug (stable dose >/= 2 weeks)

Exclusion Criteria:

• Active ischemia (acute thrombus, dynamic ST elevation on ECG) or another reversible cause of VT (eg. electrolyte abnormalities, drug induced arrhythmia)
• Are known to be ineligible to take amiodarone (eg. active hepatitis, current hyperthyroidism, pulmonary fibrosis, known allergy)
• Are ineligible for ablation (left ventricular thrombus, implanted mechanical aortic and mitral valves)
• Renal Failure (creatinine clearance < 15 ml/min)
• Current NYHA functional class IV heart failure or CCS Functional Class IV angina
• Recent ST elevation myocardial infarction (< 1 month)
• Recent coronary bypass surgery (< 3 mon) or recent PCI (< 1 mon)
• Pregnant
• prior ablation for ventricular tachycardia
• A systemic illness likely to limit survival to < 1 year
• Unable or unwilling to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ventricular Tachycardia Ablation; Catheter ablation for Ventricular tachycardia will be performed within 14 days of randomization.	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: Escalated Antiarrhythmic Drug Therapy; Patients are prescribed a loading dose of amiodarone or the addition of mexiletine to their current anti-arrhythmic medication which is stratified by the dose and type of antiarrhymic medication at the time of the index arrhythmic event.	Drug: Escalated Antiarrhythmic Therapy; Patients who have 'failed' antiarrhythmic therapy (except amiodarone) will be prescribed: Amiodarone 400 mg twice daily for 2 weeks, followed by 400 mg/day for 4 weeks, followed by 200 mg/day thereafter. Patients who 'failed' amiodarone (less than 300mg/day) will be prescribed: Amiodarone 400 mg three times a day for 2 weeks, followed by 400 mg/day for 1 week and 300 mg/day thereafter. Patients who 'failed' amiodarone (greater or equal to 300mg/day) will be prescribed: Amiodarone at the current dose with the addition of mexiletine 400 to 800 mg/day; Other Names: Cordarone; Mexetil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Appropriate ICD shocks,VT storm and death	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
All cause mortality	3 years
Appropriate ICD antitachycardia pacing anytime and after 1 month treatment period	3 years
appropriate ICD shocks anytime and after 1 month treatment period	3 years
Inappropriate shocks anytime and after 1 month treatment period	3 years
VT storm anytime and after 1 month treatment period	3 years
Documented sustained VT below detection rate of the ICD any time and after 1 month treatment period	3 years
Number of ICD shocks	3 years
Hospital admission for cardiac causes	3 years
Procedural complications, amiodarone toxicity or adverse events	3 years

Collaborators and Investigators

• Sponsor: John Sapp
• Collaborators: Canadian Institutes of Health Research (CIHR); Abbott Medical Devices; Biosense Webster, Inc.
• Investigators: Principal Investigator: John L Sapp, BSc, MD, FRCPC, Nova Scotia Health Authority; Study Director: Ratika Parkash, MD, MSc, FRCPC, Nova Scotia Health Authority; Study Director: Anthony S Tang, MSc, MD, FRCPC, Royal Jubilee Hospital; Study Director: George A Wells, BSc,MSc,PhD, Univeristy of Ottawa Heart Institute

Publications and helpful links

General Publications

• Parkash R, Nault I, Rivard L, Gula L, Essebag V, Nery P, Tung S, Raymond JM, Sterns L, Doucette S, Wells G, Tang ASL, Stevenson WG, Sapp JL. Effect of Baseline Antiarrhythmic Drug on Outcomes With Ablation in Ischemic Ventricular Tachycardia: A VANISH Substudy (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease). Circ Arrhythm Electrophysiol. 2018 Jan;11(1):e005663. doi: 10.1161/CIRCEP.117.005663.
• Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin JF, Thibault B, Rivard L, Gula L, Leong-Sit P, Essebag V, Nery PB, Tung SK, Raymond JM, Sterns LD, Veenhuyzen GD, Healey JS, Redfearn D, Roux JF, Tang AS. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med. 2016 Jul 14;375(2):111-21. doi: 10.1056/NEJMoa1513614. Epub 2016 May 5.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: May 20, 2009
• First Submitted That Met QC Criteria: May 20, 2009
• First Posted (ESTIMATE): May 21, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): July 11, 2016
• Last Update Submitted That Met QC Criteria: July 8, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Catheter Ablation; Ischemic Heart Disease; Ventricular Tachycardia; Antiarrhythmic Drug Therapy; ICD therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Tachycardia; Tachycardia, Ventricular; Molecular Mechanisms of Pharmacological Action; Vasodilator 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; Potassium Channel Blockers; Amiodarone; Anti-Arrhythmia Agents
• Other Study ID Numbers: Sapp001

Plan for Individual participant data (IPD)

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