Comparing Pulmonary Vein Isolation to Pulmonary Vein Isolation + OPTIMA Ablation in Patients Undergoing Ablation for Atrial Fibrillation

NCT04101539 | Completed DMC FDA Device

• 2 other identifiers: IRB00183327U01HL141074
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Catheter ablation is an established cornerstone of therapy for patients with symptomatic atrial fibrillation (AF) who wish to avoid anti-arrhythmic drug therapy or for whom anti-arrhythmics have proven ineffective. Pulmonary vein isolation (PVI), in which circumferential ablation is performed around the ostia of the pulmonary vein - left atrial junctions, is the standard ablation approach internationally. Single-procedure success rates (1y, freedom from AF, off anti-arrhythmics) for patients with paroxysmal AF is roughly 70%, and even worse (roughly 50%) for patients with persistent AF. A number of strategies have been developed to improve outcomes in patients undergoing AF ablation, particularly in patients with persistent AF. Unfortunately, large prospective randomized trials (including STAR-AF II, published in NEJM in 2015) have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone. In a collaborative effort between the Cardiology electrophysiology group and the Trayanova laboratory (Biomechanical Engineering), investigators have developed a strategy of patient-specific modeling to identify pro-arrhythmic sites in AF patients that may be amenable to ablation. In this approach, patients undergo a pre-ablation cardiac MRI with late gadolinium enhancement, to delineate regions of healthy atrial tissue and regions of scar (this scan is clinically indicated, and performed currently in patients undergoing PVI for AF). A novel in silico modeling to determine regions supporting electrical reentry in the atrium, driving ongoing AF, has been developed by the Trayanova lab. In preliminary studies, investigators have demonstrated the ability to identify and target these regions with catheter ablation in patients undergoing PVI. Investigators would like to conduct a prospective, randomized clinical trial in patients undergoing ablation for symptomatic persistent AF. All patients enrolled would undergo standard pre-procedure imaging (LGE-MRI) prior to the day of procedure. Investigators have developed methodology termed OPTIMA (OPtimal Target Identification via Modeling of Arrhythmogenesis) to determine, based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI (LGE-CMR) and simulation of cardiac electrical function, personalized ablation targets for persistent AF in patients with fibrotic remodeling.. Patients would be randomized to receiving PVI only versus PVI + OPTIMA ablation at the time of ablation. Patients would then be followed in standard clinical fashion at 3m, 6m, and 12m to assess for ablation efficacy and for procedural complications. Investigators postulate a 20% improvement in freedom from AF with PVI + OPTIMA ablation form 50% to 70% (compared to PVI alone), investigators anticipate that in 1:1 randomization, a sample size of 80 patients in each arm will yield a power calculation of 80% with an alpha of 0.05. Investigators anticipate that enrollment and 1y clinical follow-up for 160 patients (total) undergoing AF ablation will require a 4y timeline.

Conditions

Atrial Fibrillation Chronic

Keywords

catheter ablation; atrial fibrillation

Outcome Measures

Primary Outcomes (1)

• Freedom from atrial arrhythmias (>30s)

  Freedom from recurrent Atrial fibrillation (AF)/Atrial Tachycardia (AT)/Atrial Flutter (\> 30s) after 90 day blanking period. This will be measured as the percentage of the study population that is free from atrial arrhythmias during the 1y follow-up period.

  1 year

Secondary Outcomes (3)

• Change in AF burden

  1 year

• Percent participants with 70% or more reduction in AF burden

  1 year

• Freedom from major complications

  1 year

Study Arms (2)

Standard Ablation (PVI)

ACTIVE COMPARATOR

Patients in this arm will receive standard ablation for atrial fibrillation (wide-area circumferential ablation to achieve pulmonary vein isolation \[PVI\]).

Device: Standard PVI

OPTIMA Ablation

EXPERIMENTAL

Patients in this arm will receive standard PVI ablation and supplemental ablation of reentrant driver sites identified by OPTIMA analysis as sites likely supportive of persistent atrial fibrillation.

Device: OPTIMA-guided catheter ablation

Interventions

OPTIMA-guided catheter ablation DEVICE

Patients in the experimental arm will undergo supplemental ablation of OPTIMA-identified sites hypothesized to support/perpetuate chronic atrial fibrillation.

OPTIMA Ablation

Standard PVI DEVICE

Standard PVI for AF.

Standard Ablation (PVI)

Eligibility Criteria

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

You may qualify if:

• Eligible patients must be at least 18 years old at the time of enrollment.
• Patient was referred to Johns Hopkins cardiac electrophysiology division for clinically indicated catheter ablation for persistent or long standing persistent AF either for index ablation or redo ablation.
• Patient is currently on systemic anticoagulation or has no contraindication to initiate systemic anticoagulation.
• Capable of undergoing informed consent.
• A Pre-Op cardiac MRI including LGE in sinus rhythm must be performed prior to ablation and patient should be capable of undergoing cardioversion and cardiac MRI.
• MRI scan should show evidence of left atrial scarring.

You may not qualify if:

• Patient is not a suitable candidate for AF ablation.
• Patient is currently not on anticoagulation and has significant contraindications to initiate systemic anticoagulation.
• Pregnant women may not participate in the study because gadolinium MRI contrast is contraindicated in pregnancy.
• Patient with Body weight more than 300 lbs as they cannot undergo MRI scans.
• Patients with Glomerular Filtration Rate (GFR) \< 30 mL/min should not be enrolled in the study due to the use of intravenous gadolinium as an MRI contrast agent.
• No evidence of Left Arial fibrosis in MRI scan as these images are not suitable for simulation.
• Inability to get MRI in sinus rhythm.
• Long standing persistent AF more than 3 years of duration.
• Prior surgical maze procedure.

Sponsors & Collaborators

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

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

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

Study Officials

• David Spragg, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Blinding of patient and outcomes assessor to ablation protocol.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, controlled

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: September 24, 2019
• Study Start: September 1, 2019
• Primary Completion: September 30, 2025
• Study Completion: October 1, 2025
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)