Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation

NCT ID: NCT02608099

Last Updated: 2020-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2017-04-30

Brief Summary

The purpose of the prospective, randomized cohort in this study is to assess the safety and efficacy of 2 apixaban treatment strategies (uninterrupted versus interrupted) in subjects planned to undergo catheter ablation for the treatment of non-valvular atrial fibrillation (NVAF).

Simultaneously, a retrospective cohort of 300 warfarin-treated individuals, identified by chart review, who are matched to the prospective randomized subjects, will be identified. The purpose of the retrospective warfarin cohort is to compare the efficacy and safety of warfarin(the current clinical practice) to that of apixaban (uninterrupted, interrupted, combined uninterrupted and interrupted).

Detailed Description

Prospective, Randomized Cohort

Subjects undergoing ablation for NVAF who meet all eligibility criteria and sign informed consent will be enrolled into the study. Subjects will be treated with apixaban for ≥21 days prior to the ablation procedure (for subjects already on apixaban for ≥21 days, it is not necessary to wait 21 days before the ablation procedure. Apixaban dose will be 5 mg b.i.d. per product label, or 2.5 mg b.i.d. in subjects with 2 or more of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.

Eligible subjects will then be randomized in a 1:1 ratio to 2 peri-procedural treatment strategies:

• Uninterrupted treatment: administer the evening apixaban dose on the day prior to the procedure; administer the morning apixaban dose on the day of the procedure; administer heparin bolus before transseptal puncture to maintain a target activated clotting time [ACT] > 300 seconds; administer the evening apixaban dose after the procedure if there were no peri-procedural complications that necessitate withholding anticoagulation for longer duration.
• Interrupted treatment: administer the evening apixaban dose on the day prior to the procedure; do not administer the morning apixaban dose on the day of the procedure; administer heparin bolus before transseptal puncture to maintain a target ACT > 300 seconds; administer the evening apixaban dose after the procedure if there were no peri-procedural complications that necessitate withholding anticoagulation for longer duration.

Randomization will take place prior to the procedure (on the day of the procedure or up to 3 days prior to the procedure) and will be stratified by site.

It is anticipated that up to 360 subjects may be enrolled in order to evaluate a total of 300 randomized subjects (150 subjects per treatment arm):

Randomized subjects will continue treatment with apixaban for 1 month post procedure.

Retrospective, Warfarin Cohort In addition, a chart review of 300 warfarin-treated patients who underwent catheter ablation for NVAF on or after September 1, 2013 in the enrolling centers and who have documented follow-up in the medical record for ≥ 30 days post-ablation procedure will be performed. Patient records for warfarin-treated individuals who meet the applicable inclusion/exclusion criteria and who are matched 1:1 to a subject in the prospective, randomized cohort for age (+/- 5 years), gender and atrial fibrillation (AF) type (paroxysmal vs. persistent), will be identified. Sites will document key demographic and outcome variables. This review will be performed in a blinded manner such that site personnel are blinded to the outcome of each retrospective subject during the subject selection process. Only pre-existing data will be collected for the analysis of this cohort.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interrupted apixaban

Apixaban dose is administered on the evening prior to the procedure; apixaban dose is held on the morning of the procedure; apixaban dose is administered on the evening after the procedure if there were no peri-procedural complications that necessitated withholding anticoagulation for longer duration.

Group Type: ACTIVE_COMPARATOR

Interrupted apixaban

Intervention Type: DRUG

Apixaban dose is administered on the evening prior to the procedure; apixaban dose is held on the morning of the procedure; apixaban dose is administered on the evening after the procedure if there were no peri-procedural complications that necessitated withholding anticoagulation for longer duration.

Uninterrupted apixaban

Apixaban dose is administered on the evening prior to the procedure; apixaban dose is administered on the morning of the procedure; apixaban dose is administered on the evening after the procedure if there were no peri-procedural complications that necessitated withholding anticoagulation for longer duration.

Group Type: EXPERIMENTAL

Uninterrupted apixaban

Intervention Type: DRUG

Intervention description: Apixaban dose is administered on the evening prior to the procedure; apixaban dose is administered on the morning of the procedure; apixaban dose is administered on the evening after the procedure if there were no peri-procedural complications that necessitated withholding anticoagulation for longer duration.

Interventions

Interrupted apixaban

Apixaban dose is administered on the evening prior to the procedure; apixaban dose is held on the morning of the procedure; apixaban dose is administered on the evening after the procedure if there were no peri-procedural complications that necessitated withholding anticoagulation for longer duration.

Intervention Type: DRUG

Uninterrupted apixaban

Intervention description: Apixaban dose is administered on the evening prior to the procedure; apixaban dose is administered on the morning of the procedure; apixaban dose is administered on the evening after the procedure if there were no peri-procedural complications that necessitated withholding anticoagulation for longer duration.

Intervention Type: DRUG

Other Intervention Names

Interrupted Eliquis; Uninterrupted Eliquis

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent.

2. >18 years of age.

3. NVAF with planned catheter ablation treatment.

4. Planned anticoagulant treatment for at least 1 month after the index procedure.

5. Subject agrees to all required follow-up procedures and visits.

6. For women of childbearing potential (WOCBP):

• Must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
• Must not be breastfeeding
• Must agree to follow instructions for method(s) of contraception for a total of 33 days post-treatment completion.

7. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a total of 93 days post-treatment completion.

8. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as described in this section.

Exclusion Criteria

1. History of significant bleeding diathesis or coagulopathy or inability to accept blood transfusions.

2. Known hypersensitivity or contraindication to heparin or apixaban.

3. Subjects with mechanical prosthetic heart valves.

4. History of cerebrovascular accident or transient ischemic attach (TIA) within the last 6 months.

5. Prior intracranial hemorrhage.

6. End-stage renal failure (creatinine clearance rate <15 mL/minute or on dialysis treatment).

7. Hepatic disease associated with coagulopathy.

8. Current or expected systemic treatment with strong dual inducers of CYP3A4 and P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort).

9. Current or expected systemic treatment with dual antiplatelet therapy, other anticoagulants, or fibrinolytics.

10. Planned or expected surgery, or other invasive procedure that would require interruption of anticoagulation within 1 month of the catheter ablation procedure.

11. Currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints.

12. Co-morbid condition(s) that could limit the subject's ability to participate in the trial or to comply with follow-up requirements, or that could impact the scientific integrity of the trial.

13. Platelet count ≤100,000/mm3.

14. Hemoglobin level <9 g/dL.

15. Any active bleeding.

16. Prisoners or subjects who are involuntarily incarcerated.

17. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Baim Institute for Clinical Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Reynolds, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Lahey Hospital & Medical Center

Christopher P Cannon, MD

Role: PRINCIPAL_INVESTIGATOR

Harvard Clinical Research Organization and Cardiovascular Division Brigham and Women's Hospital

Locations

Site 0020

Huntsville, Alabama, United States

Site 0005

Mission Viejo, California, United States

Site 0012

New Haven, Connecticut, United States

Site 0011

Trumbull, Connecticut, United States

Site 0016

Pensacola, Florida, United States

Site 0014

West Des Moines, Iowa, United States

Site 0018

Bangor, Maine, United States

Site 0004

Scarborough, Maine, United States

Site 0008

Boston, Massachusetts, United States

Site 0001

Burlington, Massachusetts, United States

Site 0006

Kansas City, Missouri, United States

Site 0021

Omaha, Nebraska, United States

Site 0019

Albuquerque, New Mexico, United States

Site 0002

Toledo, Ohio, United States

Site 0007

Oklahoma City, Oklahoma, United States

Site 0009

Philadelphia, Pennsylvania, United States

Site 0010

Charleston, South Carolina, United States

Site 0017

Austin, Texas, United States

Site 0003

Richmond, Virginia, United States

Countries

United States

References

Bawazeer GA, Alkofide HA, Alsharafi AA, Babakr NO, Altorkistani AM, Kashour TS, Miligkos M, AlFaleh KM, Al-Ansary LA. Interrupted versus uninterrupted anticoagulation therapy for catheter ablation in adults with arrhythmias. Cochrane Database Syst Rev. 2021 Oct 21;10(10):CD013504. doi: 10.1002/14651858.CD013504.pub2.

Reference Type: DERIVED

PMID: 34674223 (View on PubMed)

Reynolds MR, Allison JS, Natale A, Weisberg IL, Ellenbogen KA, Richards M, Hsieh WH, Sutherland J, Cannon CP. A Prospective Randomized Trial of Apixaban Dosing During Atrial Fibrillation Ablation: The AEIOU Trial. JACC Clin Electrophysiol. 2018 May;4(5):580-588. doi: 10.1016/j.jacep.2017.11.005. Epub 2017 Dec 20.

Reference Type: DERIVED

PMID: 29798783 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

CV185-373

Identifier Type: -

Identifier Source: org_study_id