Evaluation of Conventional Ablation With or Without Focal Impulse and Rotor Modulation to Eliminate Human AF

NCT02456233 | Completed DMC

• 2 other identifiers: RECONFIRM2015K24HL103800
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 2

Brief Summary

This prospective randomized study will assess the safety and efficacy of FIRM-guided ablation (FIRM+PVI) compared to pulmonary vein isolation (PVI) without FIRM, for the treatment of symptomatic atrial fibrillation.

Conditions

Atrial Fibrillation

Keywords

rotor; FIRM; paroxysmal atrial fibrillation; persistent atrial fibrillation; atrial tachyarrhythmia; ablation; contact mapping; clinical trial; signal processing

Outcome Measures

Primary Outcomes (1)

• Long term success

  Freedom from atrial fibrillation (AF) recurrence during the 12 months after the initial AF ablation procedure, after an initial 3 month blanking (healing and stabilization) period.

  12 months

Secondary Outcomes (5)

• Long-term freedom from AF/AT

  12 months

• Total ablation time

  1 day

• Quality of Life (comparing post-ablation to pre-ablation)

  12 months

• Adverse Events

  12 months

• Healthcare Utilization

  12 months

Study Arms (2)

Conventional AF Ablation with PVI

ACTIVE COMPARATOR

These patients will be treated by conventional AF ablation by pulmonary vein isolation (PVI) alone.

Procedure: Conventional AF Ablation with PVI

FIRM-guided ablation plus PVI

EXPERIMENTAL

These patients will be treated by ablation of patient-specific rotors and focal sources (FIRM). Conventional ablation (PVI) will then be performed as part of the standard of care procedure.

Procedure: FIRM-guided ablation plus PVI

Interventions

Conventional AF Ablation with PVI PROCEDURE

Trigger Based Ablation for AF, using Pulmonary Vein Isolation (PVI) alone

Conventional AF Ablation with PVI

FIRM-guided ablation plus PVI PROCEDURE

Substrate ablation for AF, via ablation of rotors and focal sources. Conventional (PVI) ablation will also be performed.

FIRM-guided ablation plus PVI

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>21 years
• Reported incidence of at least two documented episodes of symptomatic paroxysmal or persistent atrial fibrillation (AF) during the 3 months preceding trial entry (at least one episode documented by 12-lead ECG or ECG rhythm strip). Ideally, patients will have implanted continuous ECG recorders in place for \>30 days prior to the procedure to document AF episodes and percentage of time in AF ("burden") prior to ablation
• Male -or- Women without childbearing potential (surgically sterile or have been without a period for 12 months), -or- Women of childbearing potential who are not pregnant per a serum HCG lab 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 (CHA2DS2VASc)
• congestive heart failure (1 point)
• hypertension (1 point)
• age 75 years or older (2 points)
• diabetes (1 point)
• prior stroke or transient ischemic attack (2 points)
• vascular disease (including coronary artery disease, CAD) (1 point)
• age 65 years or older (1 point)
• gender category: female (1 point) Pre-procedural anticoagulation will ideally have been continuous for 3 or more weeks prior to the procedure, as clinically indicated, with INR \> 2 in patients taking warfarin.
• 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 CHA2DS2VASc score \>or= 2

You may not qualify if:

• Reversible Cause of Atrial Fibrillation: Atrial fibrillation from a reversible cause (e.g., surgery, hyperthyroidism, pericarditis); Cardiac or thoracic surgery (e.g., valve repair or coronary artery bypass grafting, CABG) within the last 180 days; AF secondary to electrolyte imbalance, thyroid disease
• Anti-Coagulation Contraindicated: Contraindication to Heparin; Contraindication to Warfarin or other novel oral anticoagulants (e.g., dabigatran, rivaroxabanm apixaban); History of significant bleeding abnormalities
• Clotting Diathesis: History of significant blood clotting abnormalities, systemic thrombi or systemic embolization
• Cardiac Prosthesis: ASD closure device, LAA closure device, prosthetic mitral or tricuspid valve
• Thrombus or Mass: 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 affect 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
• Severe Heart Failure: NYHA classes III, IV; Heart failure that is not stable on medical therapy; Pulmonary edema that may make planned anesthesia or sedation difficult
• Non-Stable Coronary Disease: Stable/unstable angina or ongoing myocardial ischemia; Myocardial infarction (MI) within the past 3 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 the 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, defined as LA volume index \> 60 ml/m2, in whom PVI has low success and 55 mm baskets are too small for the atria
• Planned Cardiac Surgery: If cardiac transplantation or other cardiac surgery are planned within the 12 months follow period of the trial

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Veterans Affairs Medical Center

San Diego, California, 92161, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (4)

• 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. No abstract available.

  PMID: 22386883 BACKGROUND

• Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012 Aug 14;60(7):628-36. doi: 10.1016/j.jacc.2012.05.022. Epub 2012 Jul 18.

  PMID: 22818076 BACKGROUND

• Narayan SM, Baykaner T, Clopton P, Schricker A, Lalani GG, Krummen DE, Shivkumar K, Miller JM. Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow-up of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation). J Am Coll Cardiol. 2014 May 6;63(17):1761-8. doi: 10.1016/j.jacc.2014.02.543. Epub 2014 Mar 13.

  PMID: 24632280 BACKGROUND

• Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, Albenque JP, Nardi S, Menardi E, Novak P, Sanders P; STAR AF II Investigators. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015 May 7;372(19):1812-22. doi: 10.1056/NEJMoa1408288.

  PMID: 25946280 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sanjiv Narayan, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Director of AF Program and EP Research

Study Record Dates

• First Submitted: May 24, 2015
• First Posted: May 28, 2015
• Study Start: April 1, 2016
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

US (2)