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

Atrial Fibrillation Clinical Trial

— AEIOU  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02608099
• Other study ID #: CV185-373
• Status: Completed
• Phase: Phase 4
• Start date: November 2015
• Est. completion date: April 2017

Study information

• Verified date: March 2020
• Source: Baim Institute for Clinical Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Site 0019	Albuquerque	New Mexico
United States	Site 0017	Austin	Texas
United States	Site 0018	Bangor	Maine
United States	Site 0008	Boston	Massachusetts
United States	Site 0001	Burlington	Massachusetts
United States	Site 0010	Charleston	South Carolina
United States	Site 0020	Huntsville	Alabama
United States	Site 0006	Kansas City	Missouri
United States	Site 0005	Mission Viejo	California
United States	Site 0012	New Haven	Connecticut
United States	Site 0007	Oklahoma City	Oklahoma
United States	Site 0021	Omaha	Nebraska
United States	Site 0016	Pensacola	Florida
United States	Site 0009	Philadelphia	Pennsylvania
United States	Site 0003	Richmond	Virginia
United States	Site 0004	Scarborough	Maine
United States	Site 0002	Toledo	Ohio
United States	Site 0011	Trumbull	Connecticut
United States	Site 0014	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Baim Institute for Clinical Research	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Patients With Clinically-Significant Bleeding	Clinically significant bleeding was defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With Major Bleeding	Major bleeding was defined as bleeding meeting BARC criteria type 3 or higher.	Randomization to 1 month post catheter ablation
Other	Number of Patients With Major Bleeding	Major bleeding was defined as bleeding meeting BARC criteria type 3 or higher.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With Thrombotic Events	Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With Composite of Clinically Significant Bleeding and Thrombotic Events	Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.; Clinically significant bleeding was defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With Composite of Major Bleeding and Thrombotic Events	Thrombotic events are defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.; Major bleeding is defined as bleeding meeting BARC criteria type 3 or higher.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With TIAs or Non-Hemorrhagic Strokes	Number of Patients who had TIAs or non-hemorrhagic strokes.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With TIAs or Non-Hemorrhagic Strokes	This measurement includes TIAs or non-hemorrhagic strokes.	Randomization to 1 month post catheter ablation
Other	Number of Patients With Death	Death is included in this measurement.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With Cardiovascular Death	Cardiovascular death is included in this measurement.	Enrollment to 1 month post catheter ablation
Other	Number of Patients With Death	Death is included in this measurement.	Randomization to 1 month post catheter ablation
Other	Number of Patients With Cardiovascular Death	Cardiovascular death is included in this measurement.	Randomization to 1 month post catheter ablation
Primary	Number of Patients With Clinically-Significant Bleeding	Clinically significant bleeding was defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher.	Randomization to 1 month post catheter ablation
Primary	Number of Patients With Thrombotic Events	Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.	Randomization to 1 month post catheter ablation
Secondary	Number of Patients With Composite of Major Bleeding and Thrombotic Events	Major bleeding was defined as bleeding meeting BARC criteria type 3 or higher. Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.	Randomization to 1 month post catheter ablation
Secondary	Number of Patients With Composite of Clinically Significant Bleeding and Thrombotic Events	Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.; Clinically significant bleeding was defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher.	Randomization to 1 month post catheter ablation

External Links

•   The AEIOU Trial Published Manuscript