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Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation (AEIOU)

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ClinicalTrials.gov Identifier: NCT02608099
Recruitment Status : Completed
First Posted : November 18, 2015
Last Update Posted : May 10, 2017
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Baim Institute for Clinical Research

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).


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Interrupted apixaban Drug: Uninterrupted apixaban Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation
Study Start Date : November 2015
Actual Primary Completion Date : April 2017
Actual Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Apixaban

Arm Intervention/treatment
Active Comparator: 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.
Drug: 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.
Other Name: Interrupted Eliquis

Experimental: 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.
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.
Other Name: Uninterrupted Eliquis




Primary Outcome Measures :
  1. Clinically-significant bleeding [ Time Frame: Randomization to 1 month post catheter ablation ]
    Clinically significant bleeding is defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher

  2. Thrombotic events [ Time Frame: Randomization to 1 month post catheter ablation ]
    Thrombotic events are defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events


Secondary Outcome Measures :
  1. Composite of major bleeding and thrombotic events [ Time Frame: Randomization to 1 month post catheter ablation ]
    Major bleeding is defined as bleeding meeting BARC criteria type 3 or higher. Thrombotic events are defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.

  2. Composite of major bleeding and thrombotic events [ Time Frame: Enrollment to 1 month post catheter ablation ]
    Major bleeding is defined as bleeding meeting BARC criteria type 3 or higher. Thrombotic events are defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.

  3. Composite of clinically-significant bleeding and thrombotic events [ Time Frame: Randomization to 1 month post catheter ablation ]
    Clinically significant bleeding is defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher. Thrombotic events are defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.

  4. Composite of clinically-significant bleeding and thrombotic events [ Time Frame: Enrollment to 1 month post catheter ablation ]
    Clinically significant bleeding is defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher. Thrombotic events are defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.



Information from the National Library of Medicine

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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:

  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.

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): NCT02608099


  Show 19 Study Locations
Sponsors and Collaborators
Baim Institute for Clinical Research
Bristol-Myers Squibb
Investigators
Principal Investigator: Matthew Reynolds, MD, MSc Lahey Hospital & Medical Center
Principal Investigator: Christopher P Cannon, MD Harvard Clinical Research Organization and Cardiovascular Division Brigham and Women's Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Baim Institute for Clinical Research
ClinicalTrials.gov Identifier: NCT02608099     History of Changes
Other Study ID Numbers: CV185-373
First Posted: November 18, 2015    Key Record Dates
Last Update Posted: May 10, 2017
Last Verified: September 2016

Keywords provided by Baim Institute for Clinical Research:
Atrial fibrillation
Non-valvular atrial fibrillation
Catheter ablation
Apixaban
Warfarin
Harvard Clinical Research Institute

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Apixaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants