The Substrate and Intervention Mechanisms for Persistent Atrial Fibrillation Trial (SIMPle-AF)
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|ClinicalTrials.gov Identifier: NCT02918396|
Recruitment Status : Terminated (Due to low enrollment of participants meeting eligibility criteria)
First Posted : September 29, 2016
Results First Posted : January 4, 2018
Last Update Posted : January 4, 2018
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with increasing morbidity and mortality. A catheter-based AF ablation technique that isolates pulmonary veins (PV) from the left atrium has been established to disrupt AF. Despite significant development, AF ablation with pulmonary vein isolation (PVI) is reported to have a success rate of 40-80% in various AF populations.
Persistent AF appears to be more reliant upon fibroblast proliferation and myocyte-fibroblast coupling than paroxysmal AF with obvious implications on its management. Despite the knowledge that fibrotic substrate is responsible for the perpetuation of persistent AF, several ablation techniques targeting these extra-pulmonary veins sites have failed to prove an additional benefit to PVI alone. Nevertheless, two recently developed technologies, aimed at detecting AF substrate with high precision, seem to constitute a potential breakthrough in the management of persistent AF. On one hand, late gadolinium-enhanced MRI (LGE-MRI) is a well-established method to identify fibrosis in the myocardium. Recent reports from a single center have shown that MRI-based left atrial fibrosis detection is able to predict the outcome of the procedure. Hence, targeting lesions seen on LGE-MRI in the setting of persistent AF is an option yet to be explored and compared to the widely adopted, yet suboptimal, PVI. On another hand, a novel ablation method with promising results is focal impulse and rotor modulation (FIRM). Undergoing wide sampling of the atria with spatiotemporal and computational mapping while in AF has identified areas with stable organized rotational electrical activity (rotors). Several studies are under way to prove the reproducibility of rotor mapping, with more groups reporting improved rates of acute and long-term suppression of AF with ablation of FIRM-identified rotors.
The SIMPle AF study will be a randomized clinical trial designed to test the hypothesis that ablation tailored to the underlying substrate using either LGE-detected dense scar or rotor anchor sites predicted by computational modeling is superior to anatomic non-tailored PVI ablation in patients with persistent AF. For the present study, the investigators plan to enroll a total of 30 patients.
|Condition or disease||Intervention/treatment||Phase|
|Persistent Atrial Fibrillation||Device: Scar-Based Radio-frequency Ablation Device: Rotor Anchors Radio-frequency Ablation Device: Conventional PVI by Radio-frequency Ablation||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Substrate and Intervention Mechanisms for Persistent Atrial Fibrillation (SIMPle AF) Trial|
|Study Start Date :||April 2016|
|Actual Primary Completion Date :||October 2017|
|Actual Study Completion Date :||October 2017|
Active Comparator: Conventional PVI
Conventional PVI by Radio-frequency Ablation: Wide area circumferential pulmonary vein isolation (PVI) only (current standard of care) using radio-frequency ablation catheters.
Device: Conventional PVI by Radio-frequency Ablation
Conventional wide area circumferential ablation (WACA) pulmonary vein isolation will be performed using a contact-force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.
Experimental: PVI + Scar-based ablation
Scar-Based Radio-frequency Ablation: Pulmonary vein isolation followed by targeting, using radio-frequency ablation, of dense LGE sites on MRI, which are confirmed on bipolar mapping to have voltage <0.3 mV.
Device: Scar-Based Radio-frequency Ablation
Left atrial (LA) myocardium will be manually segmented prior to the procedure and 3D-volumes of the atrial anatomy with superimposed dense LGE maps will be generated. Prior to the PVI, a dense voltage map of the left atrium will be performed (>1000 points) iin sinus rhythm. After PVI, low voltage areas (defined as <0.3 mV) which are superimposed on dense LGE on the MRI will be targeted by radio frequency ablation with a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.
Experimental: PVI + Modeling-predicted rotors ablation
Rotor Anchors Radio-frequency Ablation: Pulmonary vein isolation followed by radio-frequency ablation of rotor anchors predicted by modeling.
Device: Rotor Anchors Radio-frequency Ablation
Left atrial (LA) myocardium will be manually segmented prior to the procedure and the LA shell, along with the LGE-MRI will be sent to the biomedical engineering team who will generate a 3D-model of the LA along with rotor anchor sites predicted by modeling. After the PVI, the 3D models will be displayed and the rotor anchor sites will be targeted by radiofrequency ablation with a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.
- Recurrence of Atrial Fibrillation (AF) > 30 Seconds [ Time Frame: Following the 90 day blanking period up to 12 months post-index pulmonary vein isolation ]Primary outcome is defined as symptomatic or asymptomatic AF of at least 30 seconds duration that is documented by an ECG or mobile rhythm monitoring device (AliveCor), occurring after the 3-month blanking period following catheter ablation and up to 12 months.
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): NCT02918396
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Saman Nazarian, MD, PhD||Hospital of the University of Pennsylvania; Johns Hopkins Medicine|