Substrate Versus Trigger Ablation for Paroxysmal Atrial Fibrillation (SUBSTRATE)
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|ClinicalTrials.gov Identifier: NCT02169037|
Recruitment Status : Recruiting
First Posted : June 20, 2014
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation||Procedure: FIRM Ablation Procedure: Conventional AF ablation with PVI||Not Applicable|
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 45-55%, and multiple procedure success rates of 65-75% 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, as applied to other arrhythmias. However, the relevance of AF substrates - at least in persistent AF - has been questioned with the recent STAR-AF-II trial, in which ablating at additional lines or complex atrial electrograms (CFAE) did not improve the success of PVI alone (Verma et al., 2015) - although success remained at ~50% for a single procedure. Because of STAR-AF2, the PVI limb in this trial will be PVI alone (wide area circumferential ablation) with no additional lesions.
Focal Impulse and Rotor Modulation (FIRM) is a novel approach to eliminate specific electrical substrates for AF, demonstrated in 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 PVI ablation sites and in right atrium, and ablating them has substantially improved the single procedure success rate of PVI in several multi center non-randomized trials (Narayan, J Am Coll Cardiol. 2012; Miller, J Cardiovasc Electrophysiol. 2014).
There is therefore equipoise in the literature between PVI alone, with a long-history but suboptimal results, and FIRM only, that is newer with potentially greater efficacy but without randomized trial data.
This study will test both strategies in a randomized controlled fashion.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Substrate Ablation (Focal Impulse and Rotor Modulation) Compared to Pulmonary Vein Isolation to Eliminate Paroxysmal Atrial Fibrillation: A Randomized Clinical Trial|
|Actual Study Start Date :||February 1, 2016|
|Estimated Primary Completion Date :||September 30, 2020|
|Estimated Study Completion Date :||September 30, 2021|
Experimental: FIRM ablation
These patients will be treated by ablation of patient-specific rotors and focal sources (FIRM) alone.
Procedure: FIRM Ablation
Substrate ablation for AF, via ablation of rotors and focal sources alone.
Active Comparator: Conventional AF ablation with PVI
These patients will treated by conventional AF ablation by pulmonary vein isolation (PVI) alone.
Procedure: Conventional AF ablation with PVI
Trigger Based Ablation for AF, using Pulmonary Vein Isolation alone.
- Long term success [ Time Frame: 12 months ]Freedom from AF recurrence during 12 months after the initial AF ablation procedure, after an initial 3 month blanking (healing and stabilization) period
- Long-term freedom from AF/AT [ Time Frame: 12 months ]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 ]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 ]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 ]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.
- Consistency of Sources At Repeat Ablation [ Time Frame: 2 years ]Any patient with a recurrence who consents to restudy will have an assessment of whether rotors and focal sources lie at the same locations as they did at original study.
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): NCT02169037
|Contact: Sanjiv M Narayan, MD, PhD||6507236393|
|Contact: Kathleen C Mills, BA||6507236393|
|United States, California|
|Palo Alto, California, United States, 94304|
|Contact: Paul J Wang, MD email@example.com|
|Contact: Sanjiv M Narayan, MD, PhD|
|Principal Investigator: Paul J Wang, MD|
|VA San Diego Medical Center||Recruiting|
|San Diego, California, United States, 92161|
|Contact: David E Krummen, MD 858-552-8585|
|Study Director:||Sanjiv M Narayan, MD, PhD||Stanford University|