Pan-Asia United States PrEvention of Sudden Cardiac Death Catheter Ablation Trial

Study Overview
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Brief Summary
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The current standard of care for ventricular tachycardia (VT) includes the use of medicine called anti-arrhythmic drugs (AADs) and Implantable Cardioverter Defibrillator (ICD) therapy. These treatments are used to terminate the irregular heartbeats and bring the heart back to a normal rhythm. Catheter ablation is a procedure used to eliminate (damage) the heart cells causing the arrhythmia. Patients eligible for this may benefit from an ablation procedure in addition to an ICD to treat their VT condition or risk of developing VT. This study aims to show that treating VT with catheter ablation, if performed preemptively at the time of ICD implantation, will reduce subsequent recurrent VT, ICD shocks, and lead to improved survival.

Detailed Description
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Subjects who meet inclusion/exclusion criteria will be entered into the randomized trial. Randomization will be 1:1 between control group and ablation group. Those randomized to the control group will receive ICD therapy and routine drug therapy (including antiarrhythmic drugs as indicated). Subjects randomized to the ablation group will receive ablation therapy plus ICD for ventricular tachycardia. Patients that refuse ICD therapy and undergo ablation only will be enrolled in a prospective registry. Follow-up will be performed prior to hospital discharge for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 1, 3, 6, 12, 18, and 24 months. Electrocardiography (ECG) will be performed pre-implant and prior to hospital discharge. Echocardiography (TTE) will be performed pre-implant and at 12 and 24 months. Patients that refuse ICD implantation will not be randomized and will be approached for inclusion into a registry if they undergo catheter ablation without an ICD. Basic demographics and medical history will be collected from registry subjects upon enrollment. Registry subjects will receive follow-up for routine clinical care every 6 months to check on their overall status. 120 subjects will be randomized. An additional 60 subjects will enrolled into the registry. As of the time protocol revision C changes were made (07Nov2016), 33 subjects have been randomized. There has not been any preliminary or interim analysis of any data at this point. The study-sponsor has not had any access to any clinical follow-up for the patients enrolled to date.

Official Title
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PAUSE-SCD: Pan-Asia United States PrEvention of Sudden Cardiac Death Catheter Ablation Trial

Conditions
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Ventricular Tachycardia (VT)

Intervention / Treatment
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* Device: Implantable Cardioverter Defibrillator (ICD)
* Procedure: Catheter Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is receiving a new implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) implant that has study required programing capabilities and is appropriate for remote monitoring. Patient who has received the ICD / CRT-D within 90 days of enrollment can also be enrolled. Patient who has a high risk of ICD shock as shown by documented Monomorphic VT (MMVT) by one or more of the following: Spontaneous MMVT Inducible MMVT during electrophysiology study, Inducible MMVT during noninvasive programmed stimulation study *Inducible MMVT is defined as MMVT > 30 seconds or requiring electrical termination (ATP or cardioversion) Patient has ejection fraction < 50% or right ventricular dysfunction Patient has a cardiomyopathy with structural heart disease of any cause Exclusion Criteria: Any history of debilitating stroke with neurologic deficit ST-segment elevation myocardial infarction or previous cardiac surgery within 60 days prior to enrollment Patient is pregnant or nursing Patient has chronic New York Heart Association (NYHA) class IV heart failure Patient has incessant VT necessitating immediate treatment Patient has ventricular tachycardia/ventricular fibrillation thought to be from channelopathies Limited life expectancy (less than one year) Patient has current class IV angina Recent coronary artery bypass graft or percutaneous coronary intervention (< 45 days) Patient is currently participating in another investigational drug or device study Known presence of intracardiac thrombi Prosthetic mitral or aortic valve or mitral or aortic valvular heart disease requiring immediate surgical intervention Major contraindication to anticoagulation therapy or coagulation disorder Left Ventricular Ejection Fraction < 15% Patient has had a previous ablation procedure for VT, excluding remote (> 3 months) outflow tract tachycardia Patient has glomerular filtration rate (GFR) < 30 mL/min/1.73m2 Patient has peripheral vascular disease that precludes left ventricular access Patient is thought to have idiopathic outflow VT as only VT Patient has a premature ventricular contraction (PVC) or VT induced cardiomyopathy that is expected to resolve with ablation and will not require an ICD Patient has reversible cause of VT Patient does not meet criteria for ICD or CRT-D

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 |
| --- | --- |
| Experimental: ICD with Ablation<br>Patient will receive an implantable cardioverter defibrillator (ICD) with catheter ablation and standard medical management. | Device: Implantable Cardioverter Defibrillator (ICD)<br>* An ICD is a battery-powered device placed under the skin that keeps track of heart rate. Thin wires connect the ICD to the heart. If an abnormal heart rhythm is detected, the device will deliver an electric shock to restore a normal heartbeat.<br>Procedure: Catheter Ablation<br>* Catheter ablation is a procedure that uses radiofrequency energy to destroy a small area of heart tissue that is causing rapid and irregular heartbeats. Destroying this tissue helps restore the heart's regular rhythm.<br>|
| Active Comparator: ICD Only<br>Patient will receive an implantable cardioverter defibrillator (ICD) and standard medical management. | Device: Implantable Cardioverter Defibrillator (ICD)<br>* An ICD is a battery-powered device placed under the skin that keeps track of heart rate. Thin wires connect the ICD to the heart. If an abnormal heart rhythm is detected, the device will deliver an electric shock to restore a normal heartbeat.<br>|
| Active Comparator: Ablation Only (Registry)<br>The registry will enroll patients who refuse an implantable cardioverter defibrillator (ICD) and are thus not randomized. This arm will assess the efficacy of catheter ablation in the absence of background ICD therapy. | Procedure: Catheter Ablation<br>* Catheter ablation is a procedure that uses radiofrequency energy to destroy a small area of heart tissue that is causing rapid and irregular heartbeats. Destroying this tissue helps restore the heart's regular rhythm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From Recurrent VT, Cardiovascular Rehospitalization, and All-cause Mortality | The primary endpoint is a composite. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From Recurrent VT | Recurrent VT is defined as any appropriate ICD therapy (shock or ATP) or documented sustained monomorphic VT >30 seconds. | 2 years | 
| Freedom From Cardiovascular Rehospitalization | Cardiovascular rehospitalization is defined as a hospital admission after the randomized procedure for heart failure, procedure-associated complication, or arrhythmia-related causes during the follow-up period. | 2 years | 
| Freedom From All-cause Mortality |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sudden Cardiac Death, ICD Therapy, VT Ablation