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Anticoagulation in AF Ablation and Effects on Neurocognitive Function

Primary Purpose

Atrial Fibrillation, Cerebrothromboembolus, Neurocognitive Function

Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Atrial Fibrillation Ablation
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Atrial Fibrillation Ablation, Cerebrothromboemboli, Neurocognitive Function

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients 18 years old and older with AF (paroxysmal or persistent) who are to undergo an elective AF ablation procedure at UCSF will be eligible for enrollment.

Exclusion Criteria:

  • Patients will be excluded if they have:
  • A contraindication of warfarin therapy (pregnancy, recent bleed, inability of have serial INR checks)
  • A contraindication or relative contraindication to interruption of anticoagulation (e.g. mechanical valve, clotting disorder such as antiphospholipid syndrome, recent history of pulmonary embolism or history of recurrent pulmonary embolism)
  • A contraindication to transesophageal echocardiogram; any contraindication to MRI
  • Have a diagnosed condition of dementia or a diagnosis that precludes accurate assessment of neurocognitive function
  • Non-English speakers
  • Inability to give informed consent.

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Interrupted Anticoagulation

Uninterrupted anticoagulation with warfarin

Arm Description

Patients randomized to undergo atrial fibrillation ablation with interrupted anticoagulation with apixaban (5mg twice daily; 2.5mg twice daily >80 years old, Cr > 1.5, wt < 60kg), rivaroxaban (20mg daily; 15mg daily CrCl < 50 mL/minute), dabigatran (150mg twice daily; 75mg twice daily CrCl < 30mL/minute), or warfarin (dosed case-by-case).

Patients randomized to undergo atrial fibrillation ablation with uninterrupted anticoagulation with warfarin (dosed case-by-case).

Outcomes

Primary Outcome Measures

Incidence of stroke
The incidence of peri-procedural stroke will be measured.
Incidence of Cerebrothromboemboli
The incidence of cerebrothromboemboli post-ablation will be measured by comparing post-procedural brain MRI to pre-procedural brain MRI.
Change in Neurocognitive Performance
Change in neurocognitive function will be measured by comparing performance on a battery of validated neurocognitive tests to pre-procedural performance.
Bleeding Complications
The incidence of intra- and post-procedural bleeding complications, specifically hemopericardium and groin access complications, will be measured.

Secondary Outcome Measures

Full Information

First Posted
April 18, 2014
Last Updated
December 10, 2014
Sponsor
University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT02120560
Brief Title
Anticoagulation in AF Ablation and Effects on Neurocognitive Function
Official Title
Uninterrupted Versus Interrupted Anticoagulation in Atrial Fibrillation Ablation - Cerebral Thromboemboli and Neurocognitive Performance
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Withdrawn
Study Start Date
July 2014 (undefined)
Primary Completion Date
July 2015 (Anticipated)
Study Completion Date
July 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, and treatment by AF ablation is quickly becoming the favored definitive therapy. Nonetheless, AF ablation comes with some risk, including bleeds related to vascular access and myocardial damage, as well as the rare incidence of clinical stroke from blood clots that travel from the heart to the brain, termed "cerebrothromboemboli." In fact, cerebrothromboemboli without any symptoms have been detected by special imaging procedures called brain magnetic resonance imaging (MRI) in as many as 22% of cases.(1-6) There remains clinical equipoise amongst experts regarding balancing the risks and benefits of continued versus interrupted blood thinning, or "anticoagulation" during AF ablation as they pertain to risk of bleed and cerebrothromboemboli prevention, respectively, and the potentially more subtle sequelae of these apparently silent cerebrothromboemboli remain unknown. In fact, both interruption and continuation of anticoagulation during AF ablation are the standard of care. The investigators will perform the first randomized trial of uninterrupted versus interrupted anticoagulation in patients undergoing AF ablation to determine if it mitigates neurologic injury. The objective of this research is to investigate the effect of continued anticoagulation for AF ablation on cerebrothromboemboli, and the neurocognitive sequelae of embolic lesions, which to this point are considered subclinical. The investigators hypothesize that continued anticoagulation will both reduce cerebrothromboemboli and mitigate any potential decline in neurocognitive function post-procedurally. The investigators also hypothesize that the incidence of cerebrothromboemboli (CTE) by MRI will mediate that difference.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Cerebrothromboembolus, Neurocognitive Function
Keywords
Atrial Fibrillation Ablation, Cerebrothromboemboli, Neurocognitive Function

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interrupted Anticoagulation
Arm Type
Active Comparator
Arm Description
Patients randomized to undergo atrial fibrillation ablation with interrupted anticoagulation with apixaban (5mg twice daily; 2.5mg twice daily >80 years old, Cr > 1.5, wt < 60kg), rivaroxaban (20mg daily; 15mg daily CrCl < 50 mL/minute), dabigatran (150mg twice daily; 75mg twice daily CrCl < 30mL/minute), or warfarin (dosed case-by-case).
Arm Title
Uninterrupted anticoagulation with warfarin
Arm Type
Active Comparator
Arm Description
Patients randomized to undergo atrial fibrillation ablation with uninterrupted anticoagulation with warfarin (dosed case-by-case).
Intervention Type
Procedure
Intervention Name(s)
Atrial Fibrillation Ablation
Intervention Description
Both treatment arms will undergo atrial fibrillation ablation.
Primary Outcome Measure Information:
Title
Incidence of stroke
Description
The incidence of peri-procedural stroke will be measured.
Time Frame
4 weeks
Title
Incidence of Cerebrothromboemboli
Description
The incidence of cerebrothromboemboli post-ablation will be measured by comparing post-procedural brain MRI to pre-procedural brain MRI.
Time Frame
1 day
Title
Change in Neurocognitive Performance
Description
Change in neurocognitive function will be measured by comparing performance on a battery of validated neurocognitive tests to pre-procedural performance.
Time Frame
approximately 4 weeks
Title
Bleeding Complications
Description
The incidence of intra- and post-procedural bleeding complications, specifically hemopericardium and groin access complications, will be measured.
Time Frame
approximately 1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients 18 years old and older with AF (paroxysmal or persistent) who are to undergo an elective AF ablation procedure at UCSF will be eligible for enrollment. Exclusion Criteria: Patients will be excluded if they have: A contraindication of warfarin therapy (pregnancy, recent bleed, inability of have serial INR checks) A contraindication or relative contraindication to interruption of anticoagulation (e.g. mechanical valve, clotting disorder such as antiphospholipid syndrome, recent history of pulmonary embolism or history of recurrent pulmonary embolism) A contraindication to transesophageal echocardiogram; any contraindication to MRI Have a diagnosed condition of dementia or a diagnosis that precludes accurate assessment of neurocognitive function Non-English speakers Inability to give informed consent.
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21726519
Citation
Deneke T, Shin DI, Balta O, Bunz K, Fassbender F, Mugge A, Anders H, Horlitz M, Pasler M, Karthikapallil S, Arentz T, Beyer D, Bansmann M. Postablation asymptomatic cerebral lesions: long-term follow-up using magnetic resonance imaging. Heart Rhythm. 2011 Nov;8(11):1705-11. doi: 10.1016/j.hrthm.2011.06.030. Epub 2011 Jul 2.
Results Reference
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PubMed Identifier
21453372
Citation
Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, Halimi F, Schade A, Froehner S, Ziegler V, Sergi D, Cesarani F, Blandino A. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol. 2011 Sep;22(9):961-8. doi: 10.1111/j.1540-8167.2011.02050.x. Epub 2011 Mar 31.
Results Reference
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PubMed Identifier
22913568
Citation
Haeusler KG, Koch L, Herm J, Kopp UA, Heuschmann PU, Endres M, Schultheiss HP, Schirdewan A, Fiebach JB. 3 Tesla MRI-detected brain lesions after pulmonary vein isolation for atrial fibrillation: results of the MACPAF study. J Cardiovasc Electrophysiol. 2013 Jan;24(1):14-21. doi: 10.1111/j.1540-8167.2012.02420.x. Epub 2012 Aug 22.
Results Reference
background
PubMed Identifier
21664090
Citation
Herrera Siklody C, Deneke T, Hocini M, Lehrmann H, Shin DI, Miyazaki S, Henschke S, Fluegel P, Schiebeling-Romer J, Bansmann PM, Bourdias T, Dousset V, Haissaguerre M, Arentz T. Incidence of asymptomatic intracranial embolic events after pulmonary vein isolation: comparison of different atrial fibrillation ablation technologies in a multicenter study. J Am Coll Cardiol. 2011 Aug 9;58(7):681-8. doi: 10.1016/j.jacc.2011.04.010. Epub 2011 Jun 12.
Results Reference
background
PubMed Identifier
22313240
Citation
Ichiki H, Oketani N, Ishida S, Iriki Y, Okui H, Maenosono R, Ninomiya Y, Matsushita T, Miyata M, Hamasaki S, Tei C. Incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation guided by complex fractionated atrial electrogram. J Cardiovasc Electrophysiol. 2012 Jun;23(6):567-73. doi: 10.1111/j.1540-8167.2011.02259.x. Epub 2012 Feb 7.
Results Reference
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Anticoagulation in AF Ablation and Effects on Neurocognitive Function

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