Substrate Versus Trigger Ablation for Atrial Fibrillation

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by University of California, San Diego
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Sanjiv Narayan, MD, PhD, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT02169037
First received: June 18, 2014
Last updated: NA
Last verified: June 2014
History: No changes posted
  Purpose

This is a prospective randomized study to assess the safety and efficacy of FIRM (Focal Impulse and Rotor Modulation)-guided ablation for the treatment of symptomatic atrial fibrillation (AF). The study hypothesis is that the efficacy of AF elimination at 1 year will be higher by ablating patient-specific AF-sustaining rotors and focal sources only by Focal Impulse and Rotor Modulation (FIRM) compared to conventional ablation (including PV isolation).


Condition Intervention
Atrial Fibrillation
Procedure: FIRM Ablation
Procedure: Conventional AF ablation with PVI

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Substrate Ablation (Focal Impulse and Rotor Modulation) Compared to Pulmonary Vein Isolation to Eliminate Human Atrial Fibrillation: A Randomized Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Long term success [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Freedom from AF recurrence during 12 months after the initial AF ablation procedure, after an initial 3 month blanking (healing and stabilization) period


Secondary Outcome Measures:
  • Long-term freedom from AF/AT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Freedom from AF and atrial tachycardia (AT) during 12 months after the initial AF ablation procedure, after an initial 3 month blanking (healing and stabilization) period. Atrial tachycardias (AT) include those arising from atrial regions where ablation was performed (such as left atrial tachycardia) as well as from regions where ablation was not performed (such as typical cavotricuspid isthmus dependent atrial flutter).

  • Total ablation time [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Time from first ablation lesion to the last lesion. Total ablation time will be recorded in all patients, measured as the cumulative application of energy from the first ablation lesion to the last lesion. These values will be compared between the FIRM-guided and conventional ablation groups. If ablation for AT/atrial flutter is pursued, this ablation time will be documented separately.

  • Quality of life (QOL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Quantitative EuroQol EQ5D scores post-ablation will be compared to those pre-ablation at all time points separately and together (ANOVA).

  • Adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Adverse events will be adjudicated by an independent Data and Safety Monitoring Board, who will determine whether they are or are not related to the procedure. The number and type of adverse events will be compared between FIRM-guided and conventional ablation groups.


Estimated Enrollment: 120
Study Start Date: October 2014
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FIRM ablation
These patients will be treated by ablation of patient-specific rotors and focal sources (FIRM) without pulmonary vein isolation (PVI).
Procedure: FIRM Ablation
Substrate ablation for AF, via ablation of rotors and focal sources.
Active Comparator: Conventional AF ablation with PVI
These patients will treated by conventional AF ablation with confirmation of pulmonary vein isolation (PVI).
Procedure: Conventional AF ablation with PVI
Trigger Based Ablation for AF, using Pulmonary Vein Isolation

Detailed Description:

Pulmonary vein isolation (PVI) is a standard of care therapy for atrial fibrillation (AF). However, it produces suboptimal results, with a single procedure success of 40-50%, and multiple procedure success rates of 60-70% in recent randomized trials. The rationale of PVI is to eliminate triggers from the Pulmonary veins. An alternative strategy is to eliminate the substrates that sustain AF after it has been triggered. This is the strategy applied to essentially all other arrhythmias, both supra-ventricular and ventricular.

Focal Impulse and Rotor Modulation (FIRM) is a novel approach to eliminate these substrates, that have been demonstrated in many studies from many laboratories to take the form of localized electrical circuits. These rotors and focal sources lie in patient-specific locations, often away from typical ablation sites, such that ablating them has been shown to substantially increase the single procedure success rate of ablation to ~80% (Narayan, J Am Coll Cardiol. 2012; Miller, J Cardiovasc Electrophysiol. 2014).

There is therefore equipoise in the literature between PVI, with a long-history but suboptimal results, and FIRM, that is newer but has potentially greater efficacy with less ablation.

This study will test both strategies in a randomized controlled fashion.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • male or female >21 years
  • reported incidence of at least two documented episodes of symptomatic paroxysmal or persistent atrial fibrillation (AF) during the three months preceding trial entry (at least one episode documented by 12-lead ECG or ECG rhythm strip)
  • women without childbearing potential or women of childbearing potential who are not pregnant per a serum HCG test
  • refractory to at least one Class I or III anti-arrhythmic medications. Drug doses must be therapeutic and stable
  • willingness, ability and commitment to participate in baseline and follow-up evaluations without participation in another clinical trial (unless documented approval received from both sponsors)
  • oral anticoagulation required for those subjects who have a score of two or more based on the following criteria (CHAD score):

    • Congestive heart failure (1 point)
    • hypertention (1 point)
    • age 75 years or older (2 points)
    • diabetes (1 point)
    • prior stroke or transient ischemic attack (2 points)
    • vascular disease (1 point)
    • age 65 years or older (1 point)
    • sex category: female (1 point)
  • patient is willing and able to remain on anti-coagulation therapy for a minimum of 3 months post procedure for all subjects, and potentially indefinitely post procedure if the patient has CHAD score >or=2
  • signed informed consent after a full discussion of the risks and benefits of both therapy arms, and the concept of randomization
  • NYHA Class 0,I, II stable on medical therapy for > 3months
  • left atrial diameter <or= 5.5cm
  • LVEF >or=40%
  • sustained AF during the procedure

EXCLUSION CRITERIA:

  • atrial fibrillation from a reversible cause (e.g., surgery, hyperthyroidism, pericarditis)
  • cardiac or thoracic surgery within the past 180 days
  • AF secondary to electrolyte imbalance, thyroid disease
  • contraindication to Heparin
  • Contraindication to Warfarin or other novel oral anticoagulants
  • history of significant bleeding abnormalities
  • history of significant blood clotting abnormalities, systemic thrombi or systemic embolization
  • ASD closure device, LAA closure device, prosthetic mitral or tricuspid valve
  • atrial clot/thrombus on imaging such as on a trans-esophageal echocardiogram (TEE) within 72 hours of the procedure
  • intramural thrombus or other cardiac mass that may adversely effect catheter introduction or manipulation
  • significant pulmonary embolus within 6 months of enrollment
  • acute illness or active systemic infection or sepsis that may ordinarily warrant postponement of the procedure
  • history of recent cerebrovascular disease (stroke or TIA) or systemic thromboembolism within < 6 months
  • NYHA classes III, IV
  • heart failure that is not stable on medical therapy
  • pulmonary edema, that may make planned anesthesia or sedation difficult
  • stable/unstable angina or ongoing myocardial ischemia
  • myocardial infarction (MI) within the past three months
  • structural heart disease of clinical significance including:

    • congenital heart disease where the abnormality or its correction prohibit or increase the risk of ablation
    • acquired heart disease that may increase risk of ablation, such as significant ventricular septal defect post myocardial infarction
    • rheumatic valve disease, since this produces a unique AF phenotype
    • extreme left atrial enlargement (LA volume index > 60 ml/m2) in whom PVI has low success and 55 mm baskets are too small for the atria
  • cardiac transplantation or other cardiac surgery planned within the 12 month followup period of the trial
  • life expectancy less than 12 months (the followup period of the trial)
  • significant pulmonary disease (e.g., COPD) or any other disease that significantly increase the risk to the patient from sedation or anesthesia
  • untreatable allergy to contrast media
  • at time of ablation procedure, clinically significant abnormalities in serum potassium, sodium, magnesium or other electrolytes that affect the suitability of the patient for ablation at that time
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02169037

Contacts
Contact: Sanjiv M Narayan, MD, PhD (858) 552-8585
Contact: Kathleen C Mills, BA (858) 552-8585

Locations
United States, California
University of California, San Diego Medical Center Not yet recruiting
San Diego, California, United States, 92037
Contact: Sanjiv M Narayan, MD, PhD         
Principal Investigator: Sanjiv M Narayan, MD, PhD         
VA San Diego Medical Center Not yet recruiting
San Diego, California, United States, 92161
Contact: Sanjiv M Narayan, MD, PhD         
Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: Sanjiv M Narayan, MD, PhD University of California, San Diego
  More Information

Publications:
Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D; Heart Rhythm Society Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. 2012 Apr;9(4):632-696.e21. doi: 10.1016/j.hrthm.2011.12.016. Epub 2012 Mar 1.

Responsible Party: Sanjiv Narayan, MD, PhD, Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02169037     History of Changes
Other Study ID Numbers: NAR083359, R01HL083359
Study First Received: June 18, 2014
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
Rotor
FIRM
Atrial Fibrillation
Atrial tachyarrhythmia
Ablation
Contact mapping
Clinical trial
Signal processing.

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014