Unpinning Termination Therapy for VT/VF

Study Overview
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Brief Summary
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This study is intended to develop a better method for stopping potentially lethal heart rhythms than currently available defibrillators. This new method, called Unpinning Termination Therapy (UPT), is hypothesized to be effective in stopping these dangerous heart rhythms at lower voltages and energy than current defibrillators. Consequently, UPT may improve survival, reduce patient pain from shocks, and lead to longer lasting and smaller implantable defibrillators.

Detailed Description
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A prospective single-arm feasibility study involving acute testing of UPT electrotherapy in subjects with VT/VF during clinically indicated ventricular tachycardia catheter ablation procedure or indicated implantable cardioverter defibrillator implant, upgrade, or replacement or new CRT-D implant or upgrade to CRT-D. The study involves up to two roll in subjects at each participating site followed by an UPT evaluation and refinement segment in which remaining subjects are enrolled until arrhythmia terminations from UPT delivery are reliably achieved. A prospective evaluation segment will be performed to compare UPT against SBS and ATP if sufficient subjects remain once reliable terminations from UPT are achieved. Subjects will be evaluated at the visits for the Clinically-Indicated Procedure per standard of care. A single follow-up at up to 30 days post-procedure is required to assess subjects for adverse events.

Official Title
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An International Clinical Feasibility Study to Evaluate the Safety and Performance of Low-Energy Unpinning Termination Therapy in Patients With VT/VF

Conditions
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Ventricular Tachycardia, Ventricular Fibrillation

Intervention / Treatment
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* Device: Unpinning Termination Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Life expectancy of 1 year or greater Male or female between 18 and 75 years of age Willing and able to comply with the study protocol, provide a written informed consent Indication for an endocardial VT catheter ablation for sustained, life-threatening monomorphic VT OR an indication for VF and ICD implant (de novo implant, replacement or upgrade) OR CRT-D (de novo implant, upgrade from ICD) with transvenous leads for the risk of or presence of VT and/or VF. Etiology of arrhythmia, or risk of arrhythmia being ischemic dilated cardiomyopathy or non-ischemic idiopathic dilated cardiomyopathy both with LVEF ≤ 35% and meeting local standard of care Medically stable at time of consent to undergo DFT testing performed under general anesthesia or conscious sedation as determined by the investigator Exclusion Criteria: The subject must not meet any of the following exclusion criteria: Medically unstable at time of study and unsafe to undergo DFT testing under general anesthesia or conscious sedation as determined by the investigator Hemodynamic instability as determined by the investigator AF or atrial flutter for ≥ 48 hours or unknown duration, and no anticoagulation for preceding 3 weeks and no preoperative transesophageal echocardiographic confirmation of the absence of RA and LA thrombus AF or atrial flutter for <48 hours and no Preoperative transesophageal echocardiographic confirmation of the absence of RA and LA thrombus Presence of intracardiac thrombus Inability to pass catheters to heart due to vascular limitations Cardiovascular anatomical defects that would complicate placement of the lead or catheter required by the protocol, including congenital heart disease and cardiac vein anomalies as determined by the investigator Pregnancy confirmed by test within 7 days of procedure Pacemaker dependent The presence of a normally functioning left ventricular lead which is not planned for revision Presence of ventricular assist device, including Intra-aortic balloon pump Subjects requiring the use of I.V. inotropes and/or vasopressors for hemodynamic support in the 14 days prior to the study Prior VT catheter ablation with associated serious complication, such as hemodynamic compromise despite pressor agents, stroke, cardiac perforation, AC fistula, pneumothorax, sepsis Incessant VT/VF or VT/VF storm LVEF < 20% New York Heart Association (NYHA) Class IV heart failure Planned epicardial VT ablation on the same day as the research study History of hyper-coagulable state that could increase risk of thromboembolic events History of hemodynamic compromise due to valvular heart disease requiring IV inotropes or other circulatory support. Unstable coronary artery disease as determined by the investigator Severe proximal three-vessel or left main coronary artery disease, without revascularization as determined by the investigators History of embolic stroke, Transient Ischemic Attack or other thromboembolic event in the past 6 months History of Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Dysplasia, Congenital Heart Anomaly, Cardiac Amyloidosis, Genetic Cardiac Channelopathy or Cardiac Sarcoidosis. Cardiovascular surgery or intervention within 1 month prior to enrollment or planned for up to 1 month after enrollment (other than the planned treatment procedure) Morbid obesity: BMI>39 kg/m2 Cognitive or mental health status that would interfere with study participation and proper informed consent Presence of mechanical tricuspid valve Active Endocarditis Ventricular arrhythmia etiology sarcoidosis Valvular ventricular tachycardia Previously implanted lead is under recall by manufacturer or evidence of lead failure as determined by the investigator End Stage Renal Disease on hemodialysis or peritoneal dialysis, or estimated glomerular filtration rate (eGFR) <15 ml/min Right atrial or right ventricular lead implanted within 12 months prior to screening Any other medical condition which may affect the outcome of this study or safety of the subject as determined by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Non-randomized, non-blinded, prospective, single-arm, acute, early-feasibility study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unpinning Termination Therapy Arm<br>Subjects will have VT/VF induced and the Cardialen External Stimulation System (CESS) device will deliver electrical stimulation to terminate the arrhythmia | Device: Unpinning Termination Therapy<br>* The Cardialen External Stimulation System (CESS) is the research delivery system for the proprietary Cardialen Unpinning Therapy (UPT) therapy. The CESS is a custom designed and built research device. It is comprised of off-the-shelf commercial components (power supplies, waveform generators, laptop computer, monitor, rack, ECG system, leads, etc.) combined with a custom electrical circuit board and custom software.<br>* Other names: Multi-stage electrotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of UPT therapy | Adverse events | Study procedure and 30 day post procedure | 
| Safety of UPT therapy | Adverse events | 30 day post procedure | 
| Parameters at which UPT terminates VT and VF | Voltage | Study procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Voltage at which UPT and endocardial single biphasic shock terminate VT/VF | Voltage | Study procedure | 
| Voltage at which UPT and ATP terminate VT | Voltage | Study procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Termination, Unpinning, Therapy