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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03871231




Registration number
NCT03871231
Ethics application status
Date submitted
5/03/2019
Date registered
12/03/2019
Date last updated
24/07/2019

Titles & IDs
Public title
Unpinning Termination Therapy for VT/VF
Scientific title
An International Clinical Feasibility Study to Evaluate the Safety and Performance of Low-Energy Unpinning Termination Therapy in Patients With VT/VF
Secondary ID [1] 0 0
CL006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ventricular Tachycardia 0 0
Ventricular Fibrillation 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Unpinning Termination Therapy

Experimental: Unpinning Termination Therapy Arm - Subjects will have VT/VF induced and the Cardialen External Stimulation System (CESS) device will deliver electrical stimulation to terminate the arrhythmia


Treatment: Devices: Unpinning Termination Therapy
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.

Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety of UPT therapy - Adverse events
Timepoint [1] 0 0
Study procedure and 30 day post procedure
Primary outcome [2] 0 0
Safety of UPT therapy - Adverse events
Timepoint [2] 0 0
30 day post procedure
Primary outcome [3] 0 0
Parameters at which UPT terminates VT and VF - Voltage
Timepoint [3] 0 0
Study procedure
Secondary outcome [1] 0 0
Voltage at which UPT and endocardial single biphasic shock terminate VT/VF - Voltage
Timepoint [1] 0 0
Study procedure
Secondary outcome [2] 0 0
Voltage at which UPT and ATP terminate VT - Voltage
Timepoint [2] 0 0
Study procedure

Eligibility
Key inclusion criteria
1. Life expectancy of 1 year or greater

2. Male or female between 18 and 75 years of age

3. Willing and able to comply with the study protocol, provide a written informed consent

4. 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.

5. 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

6. Medically stable at time of consent to undergo DFT testing performed under general
anesthesia or conscious sedation as determined by the investigator
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The subject must not meet any of the following exclusion criteria:

1. Medically unstable at time of study and unsafe to undergo DFT testing under general
anesthesia or conscious sedation as determined by the investigator

2. Hemodynamic instability as determined by the investigator

3. 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

4. AF or atrial flutter for <48 hours and no Preoperative transesophageal
echocardiographic confirmation of the absence of RA and LA thrombus

5. Presence of intracardiac thrombus

6. Inability to pass catheters to heart due to vascular limitations

7. 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

8. Pregnancy confirmed by test within 7 days of procedure

9. Pacemaker dependent

10. The presence of a normally functioning left ventricular lead which is not planned for
revision

11. Presence of ventricular assist device, including Intra-aortic balloon pump

12. Subjects requiring the use of I.V. inotropes and/or vasopressors for hemodynamic
support in the 14 days prior to the study

13. Prior VT catheter ablation with associated serious complication, such as hemodynamic
compromise despite pressor agents, stroke, cardiac perforation, AC fistula,
pneumothorax, sepsis

14. Incessant VT/VF or VT/VF storm

15. LVEF < 20%

16. New York Heart Association (NYHA) Class IV heart failure

17. Planned epicardial VT ablation on the same day as the research study

18. History of hyper-coagulable state that could increase risk of thromboembolic events

19. History of hemodynamic compromise due to valvular heart disease requiring IV inotropes
or other circulatory support.

20. Unstable coronary artery disease as determined by the investigator

21. Severe proximal three-vessel or left main coronary artery disease, without
revascularization as determined by the investigators

22. History of embolic stroke, Transient Ischemic Attack or other thromboembolic event in
the past 6 months

23. History of Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Dysplasia,
Congenital Heart Anomaly, Cardiac Amyloidosis, Genetic Cardiac Channelopathy or
Cardiac Sarcoidosis.

24. 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)

25. Morbid obesity: BMI>39 kg/m2

26. Cognitive or mental health status that would interfere with study participation and
proper informed consent

27. Presence of mechanical tricuspid valve

28. Active Endocarditis

29. Ventricular arrhythmia etiology sarcoidosis

30. Valvular ventricular tachycardia

31. Previously implanted lead is under recall by manufacturer or evidence of lead failure
as determined by the investigator

32. End Stage Renal Disease on hemodialysis or peritoneal dialysis, or estimated
glomerular filtration rate (eGFR) <15 ml/min

33. Right atrial or right ventricular lead implanted within 12 months prior to screening

34. Any other medical condition which may affect the outcome of this study or safety of
the subject as determined by the investigator

Study design
Purpose of the study
Device Feasibility
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 0 0
4032 - Chermside

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cardialen, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genae
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Five Corners
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03871231
Trial related presentations / publications
Janardhan AH, Gutbrod SR, Li W, Lang D, Schuessler RB, Efimov IR. Multistage electrotherapy delivered through chronically-implanted leads terminates atrial fibrillation with lower energy than a single biphasic shock. J Am Coll Cardiol. 2014 Jan 7-14;63(1):40-8. doi: 10.1016/j.jacc.2013.07.098. Epub 2013 Sep 26.
Janardhan AH, Li W, Fedorov VV, Yeung M, Wallendorf MJ, Schuessler RB, Efimov IR. A novel low-energy electrotherapy that terminates ventricular tachycardia with lower energy than a biphasic shock when antitachycardia pacing fails. J Am Coll Cardiol. 2012 Dec 11;60(23):2393-8. doi: 10.1016/j.jacc.2012.08.1001. Epub 2012 Nov 7.
Li W, Janardhan AH, Fedorov VV, Sha Q, Schuessler RB, Efimov IR. Low-energy multistage atrial defibrillation therapy terminates atrial fibrillation with less energy than a single shock. Circ Arrhythm Electrophysiol. 2011 Dec;4(6):917-25. doi: 10.1161/CIRCEP.111.965830. Epub 2011 Oct 6.
Efimov I, Ripplinger CM. Virtual electrode hypothesis of defibrillation. Heart Rhythm. 2006 Sep;3(9):1100-2. Epub 2006 Mar 10.
Ripplinger CM, Krinsky VI, Nikolski VP, Efimov IR. Mechanisms of unpinning and termination of ventricular tachycardia. Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H184-92. Epub 2006 Feb 24.
Li W, Ripplinger CM, Lou Q, Efimov IR. Multiple monophasic shocks improve electrotherapy of ventricular tachycardia in a rabbit model of chronic infarction. Heart Rhythm. 2009 Jul;6(7):1020-7. doi: 10.1016/j.hrthm.2009.03.015. Epub 2009 Mar 11.
Ambrosi CM, Ripplinger CM, Efimov IR, Fedorov VV. Termination of sustained atrial flutter and fibrillation using low-voltage multiple-shock therapy. Heart Rhythm. 2011 Jan;8(1):101-8. doi: 10.1016/j.hrthm.2010.10.018. Epub 2010 Oct 19.
Public notes

Contacts
Principal investigator
Name 0 0
Harris Haqqani, MD
Address 0 0
The Prince Charles Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dave Munneke, MS
Address 0 0
Country 0 0
Phone 0 0
6128049516
Fax 0 0
Email 0 0
DMunneke@cardialen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03871231