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Impact of PREVENTIVE Substrate Ablation of Coronary Chronic Total Occlusion on Implantable cardioVerTer-Defibrillator Interventions (PREVENTIVE VT)

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ClinicalTrials.gov Identifier: NCT03421834
Recruitment Status : Recruiting
First Posted : February 5, 2018
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
David Žižek, MD, PhD, University Medical Centre Ljubljana

Brief Summary:
The aim of this study is to assess whether preventive substrate ablation of chronic total occlusion infarct-related artery (CTO-IRA) area in heart failure (HF) patients correlates with lower appropriate implantable cardiac defibrillator (ICD) therapies. In addition, the purpose of the study is to determine whether prophylactic substrate ablation at the time of primary ICD implantation in high-risk ischemic patients affects unplanned hospitalization, HF progression, and quality of life.

Condition or disease Intervention/treatment Phase
Ventricular Tachycardia Ischemic Cardiomyopathy Procedure: Catheter ablation of ventricular tachycardia Drug: Optimal medical treatment Not Applicable

Detailed Description:

Implantable cardioverter-defibrillators (ICDs) improve survival among patients with ischemic heart failure (HF) who have not previously had a sustained ventricular arrhythmia. However, ICD shocks that terminate ventricular tachycardia (VT) are associated with higher mortality, which may be a reflection of ICD shocks being a marker of more advanced disease versus shocks causing a worse prognosis. In addition, ICD shocks are associated with decreased functional status and quality of life. Antiarrhythmic medications (AAD) reduce ICD shocks but have high rates of side effects and lack of compliance within 1 year of initiation. Some randomized, controlled clinical trials have shown that catheter ablation (CA) of VT can decrease the number of episodes of VT and ICD shocks which could translate to an improvement in patient outcomes.

Regarding the approach to CA of VT, several controversies and gaps of knowledge can be found in the literature. Some authors target predominantly "clinical VTs" (activation and entrainment mapping), while others focus on the substrate causing VTs without focusing on VT morphologies (elimination of local abnormal ventricular activities and late potentials). In addition, data on timing of the CA procedure is inconsistent. However, early CA strategy seems feasible as end-stage cardiovascular disease increases procedural risk and is associated with arrhythmias that may be less amenable to successful treatment with ablation.

The current focus on risk stratifying patients with ischemic cardiomyopathy who could benefit from a primary prevention ICD solely on basis of ejection fraction and NYHA class is far from ideal. In patients with ischemic HF, the presence of the coronary chronic total occlusion (CTO) is related to worse long-term prognosis. Moreover, in a subgroup of ischemic patients, CTO associated with a previous infarction in its territory was an independent predictor of ventricular arrhythmias. Recent studies reported that primary prevention patients with CTO of an infarct-related artery (CTO-IRA) have a very high risk of appropriate ICD therapies due to fast VTs. As post-myocardial infarction scar is a well-recognized substrate of VTs, these patients might benefit from prophylactic substrate ablation at the time of primary ICD implantation.

Eligible and consenting patients on optimal medical HF treatment with confirmed CTO-IRA will be equally randomized to receive either a primary prevention ICD or a CA procedure and an ICD. Catheter ablation with a uniform procedural endpoint and definition of acute procedural success was to be performed before ICD implantation. ICD programming will be standardized for all subjects according to primary prevention settings.

Subjects will be seen at baseline randomization, then 1 month after ICD implantation and every 6 months thereafter until the end of the study. Subjects will be followed up for a minimum of 24 months. Quality of life questionnaires will be done at each visit.

The aim of this study is to assess whether preventive substrate ablation of CTO-IRA area in HF patients correlates with lower appropriate ICD therapies. In addition, the purpose of the study is to determine whether prophylactic substrate ablation at the time of primary ICD implantation in high-risk ischemic patients affects unplanned hospitalization, HF progression, and quality of life.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of PREVENTIVE Substrate Catheter Ablation on Implantable cardioVerter-defibrillaTor Interventions in Patients With Ischaemic Cardiomyopathy and Infarct-related Coronary Chronic Total Occlusion
Actual Study Start Date : February 6, 2018
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : February 1, 2022


Arm Intervention/treatment
Experimental: Prophylactic VT ablation prior to ICD implantation Procedure: Catheter ablation of ventricular tachycardia
Catheter ablation with a uniform mapping system, procedural endpoint, and definition of acute procedural success.

Drug: Optimal medical treatment
Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. Antiarrhythmics will be avoided if possible in the ablation group.

Active Comparator: ICD implantation and optimal medical treatment
ICD implantation and optimal medical care until at least 2 appropriate ICD shock occurs or an arrhythmic storm and catheter ablation thereafter.
Drug: Optimal medical treatment
Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. Antiarrhythmics will be avoided if possible in the ablation group.




Primary Outcome Measures :
  1. Time to first event comprising appropriate ICD therapy and unplanned hospital admission for symptomatic ventricular tachycardia (VT)/ ventricular fibrillation (VF) [ Time Frame: From randomization until official study end or drop-out, patients will be followed and assessed at least 24 months. ]
    Appropriate ICD therapy defined as shock or ATP therapy.


Secondary Outcome Measures :
  1. Time to appropriate ICD therapy [ Time Frame: At least 24 months after enrolment ]
    Appropriate ICD therapy defined as shock or ATP therapy.

  2. Incidence of appropriate ICD therapy [ Time Frame: At least 24 months after enrolment ]
  3. Time to unplanned hospital admission for symptomatic ventricular tachycardia (VT)/ ventricular fibrillation (VF) [ Time Frame: At least 24 months after enrolment ]
  4. Time to unplanned cardiac hospital admission [ Time Frame: At least 24 months after enrolment ]
  5. Time to electrical storm [ Time Frame: At least 24 months after enrolment ]
    Electrical storm defined by 3 or more sustained episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), or appropriate ICD therapy within 24 hours.

  6. Cardio-vascular mortality [ Time Frame: At least 24 months after enrolment ]
  7. Changes in quality of life using the EQ-5D questionnaire [ Time Frame: At least 24 months after enrolment ]
    EQ-5D is a standardised measure of health status consisting of 2 pages - the EQ-5D descriptive system (descriptive system with 3 levels) and the EQ visual analogue scale ranging from 0 (worst state) to 100 (best state).

  8. Psychometric evaluation of ICD shock-related anxiety using The Florida Shock Anxiety Scale (FSAS) [ Time Frame: At least 24 months after enrolment ]
    Questions were designed to capture patient opinion on perceptions of current health status, as well as a subjective opinion of how the ICD has affected them in specific areas, including anxiety levels. A higher score indicates an positive response and a lower score indicates a negative response.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ischemic cardiomyopathy with reduced ejection fraction (EF ≤ 40%) estimated by cardiac MRI or echocardiography within 30 days before enrollment
  2. Coronary Chronic Total Occlusion (CTO) associated with a previous MI confirmed by coronary angiography and late gadolinium enhancement MRI or myocardial perfusion imaging within 30 days before enrollment
  3. Implantable cardioverter-defibrillator (ICD) indication for primary prevention
  4. Patient has provided written informed consent

Exclusion Criteria:

  1. Age < 18 years or > 85 years
  2. Documented sustained ventricular tachycardia before enrollment
  3. Class IV New York Heart Association (NYHA) heart failure
  4. CTOs not associated with a prior infarction in their territory
  5. Acute myocardial infarction (MI) or acute coronary syndrome
  6. Subjects with active ischemia that are eligible for revascularization
  7. Documented history of MI less than 6 months before enrollment
  8. Patients requiring chronic renal dialysis
  9. Thrombocytopenia or coagulopathy
  10. Pre-existing implantable cardioverter-defibrillator (ICD)
  11. Pregnancy or breastfeeding women
  12. Acute illness or active systemic infection
  13. Life expectancy less than 12 months
  14. Unwillingness to participate or lack of availability for follow-up
  15. Valvular heart disease or mechanical heart valve precluding access to the left ventricle

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03421834


Contacts
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Contact: David Zizek, Assist. Prof. +38615228534 davidzizek@yahoo.com, david.zizek@kclj.si
Contact: Luka Klemen, MD +38615228528 luka.klemen@kclj.si

Locations
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Croatia
Klinički bolnički centar Sestre Milosrdnice Recruiting
Zagreb, Croatia, HR-10000
Contact: Nikola Pavlović, MD, PhD    +385 1 3787 111    nikolap12@yahoo.com   
Slovenia
General Hospital Celje Recruiting
Celje, Slovenia, 3000
Contact: Rafael Skale, MD       skaler59@gmail.com   
General Hospital Izola Recruiting
Izola, Slovenia, 6310
Contact: Jurij Avramovic-Gregoric, MD         
University Medical Centre Ljubljana - Cardiology department Recruiting
Ljubljana, Slovenia, 1000
Contact: David Zizek, Assist. Prof.       david.zizek@kclj.si   
Contact: Luka Klemen, MD       luka.klemen@kclj.si   
University Medical Centre Ljubljana - Cardiovascular surgery department Recruiting
Ljubljana, Slovenia, 1000
Contact: Matevz Jan, MD       matevz.jan@kclj.si   
Sponsors and Collaborators
University Medical Centre Ljubljana
Investigators
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Study Chair: Matjaz Sinkovec, Prof. University Medical Centre Ljubljana (Slovenia)
Study Chair: Andrej Pernat, Prof. University Medical Centre Ljubljana (Slovenia)
Principal Investigator: David Zizek, Assist. Prof. University Medical Centre Ljubljana (Slovenia)

Publications:

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Responsible Party: David Žižek, MD, PhD, Assistant Professor, Principal Investigator, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT03421834     History of Changes
Other Study ID Numbers: PREVENTIVE VT
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by David Žižek, MD, PhD, University Medical Centre Ljubljana:
Ventricular Tachycardia
Ischemic Cardiomyopathy
Primary prevention
Heart Failure
Additional relevant MeSH terms:
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Cardiomyopathies
Tachycardia
Tachycardia, Ventricular
Ischemia
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Cardiac Conduction System Disease