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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
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • History of persistent atrial fibrillation
  • Indicated for an AF-ablation procedure
  • Agree to participate in the trial

Exclusion Criteria:

  • Are unable or unwilling to provide informed consent for the SIMPle AF study
  • Patients with cardiac devices like pacemakers, internal cardiac defibrillators and Cardiac Resynchronization Therapy Device (CRT). Patients with acute or chronic renal insufficiency (glomerular filtration rate <30 ml/min/1.73 m2), or patients in the perioperative liver transplantation period
  • Pregnant women
  • Patients who are unable to adhere to the follow up protocol
  • Patients with contraindication to MRI, including ferromagnetic aneurysm clips, metal in the eye, and implanted ferromagnetic or other MRI-incompatible devices
  • Patients in whom the LGE Cardiac MRI does not meet quality standards for fibrosis analysis
  • Subjects without daily access to a smart phone or tablet compatible with the mobile-based application and ability to upload ECG tracings for the follow up period
  • Patients with a history of allergic reactions to gadolinium-based contrast agents or ingredients and will not be premedicated**

    • Subjects with a history of reaction to contrast may be premedicated according to institutional protocol prior to receiving intravenous contrast agents

Information from the National Library of Medicine

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


Locations
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Saman Nazarian, MD, PhD Hospital of the University of Pennsylvania; Johns Hopkins Medicine
  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

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. 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. Europace. 2012 Apr;14(4):528-606. doi: 10.1093/europace/eus027. Epub 2012 Mar 1.

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02918396     History of Changes
Other Study ID Numbers: IRB00084915
First Posted: September 29, 2016    Key Record Dates
Results First Posted: January 4, 2018
Last Update Posted: January 4, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Johns Hopkins University:
Atrial Fibrillation
Atrial Fibrosis
Late Gadolinium Enhancement Magnetic Resonance Imaging
Computational Modeling
Rotor Anchor Sites

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