Atrial FibrillationPhase 4AEIOUNCT02608099
Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation
A Phase 4 study testing Interrupted apixaban and Uninterrupted apixaban in people with Atrial Fibrillation, run by Baim Institute for Clinical Research at 19 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Interrupted apixaban and Uninterrupted apixaban
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 19 sitesUnited States
- Study dates
- Nov 2015to Apr 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent.
- >18 years of age.
- NVAF with planned catheter ablation treatment.
- Planned anticoagulant treatment for at least 1 month after the index procedure.
- Subject agrees to all required follow-up procedures and visits.
- For women of childbearing potential (WOCBP):
Show all 11Show fewer
- 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.
- 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.
- 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.
Who cannot join
- History of significant bleeding diathesis or coagulopathy or inability to accept blood transfusions.
- Known hypersensitivity or contraindication to heparin or apixaban.
- Subjects with mechanical prosthetic heart valves.
- History of cerebrovascular accident or transient ischemic attach (TIA) within the last 6 months.
- Prior intracranial hemorrhage.
- End-stage renal failure (creatinine clearance rate <15 mL/minute or on dialysis treatment).
Show all 17Show fewer
- Hepatic disease associated with coagulopathy.
- Current or expected systemic treatment with strong dual inducers of CYP3A4 and P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort).
- Current or expected systemic treatment with dual antiplatelet therapy, other anticoagulants, or fibrinolytics.
- Planned or expected surgery, or other invasive procedure that would require interruption of anticoagulation within 1 month of the catheter ablation procedure.
- 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.
- 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.
- Platelet count ≤100,000/mm3.
- Hemoglobin level <9 g/dL.
- Any active bleeding.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Site 0019
Albuquerque, New Mexico, 87101
Site 0017
Austin, Texas, 78705
Site 0018
Bangor, Maine, 04401
Site 0008
Boston, Massachusetts, 02118
Site 0001
Burlington, Massachusetts, 01805
Site 0010
Charleston, South Carolina, 29401
Site 0020
Huntsville, Alabama, 35801
Site 0006
Kansas City, Missouri, 64111
Site 0005
Mission Viejo, California, 92690
Site 0012
New Haven, Connecticut, 06501
Site 0007
Oklahoma City, Oklahoma, 73104
Site 0021
Omaha, Nebraska, 68131
Site 0016
Pensacola, Florida, 32501
Site 0009
Philadelphia, Pennsylvania, 19019
Site 0003
Richmond, Virginia, 23219
Site 0004
Scarborough, Maine, 04074
Site 0002
Toledo, Ohio, 43615
Site 0011
Trumbull, Connecticut, 06611
Site 0014
West Des Moines, Iowa, 50266
About this study
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).
Read the 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
- Being tested
- Interrupted apixaban, Uninterrupted apixaban
- Keywords
- Atrial fibrillation, Non-valvular atrial fibrillation, Catheter ablation, Apixaban, Warfarin, Harvard Clinical Research Institute
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interrupted apixabanDrug
Also called Interrupted Eliquis
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 apixabanDrug
Also called Uninterrupted Eliquis
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.
| Study group | Role | What they receive |
|---|---|---|
| Interrupted apixaban | Active comparator | 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. Receives: Drug: Interrupted apixaban |
| Uninterrupted apixaban | Experimental | 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. Receives: Drug: Uninterrupted apixaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Randomization to 1 month post catheter ablation
Number of Patients With Thrombotic Events
Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.
Measured: Randomization to 1 month post catheter ablation
Secondary outcomes (2)
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.
Measured: Randomization to 1 month post catheter ablation
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.
Measured: Randomization to 1 month post catheter ablation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2015 (estimated)
- Study startNov 2015
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baim Institute for Clinical Research
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Matthew Reynolds, MD, MSc, Principal investigator, Lahey Hospital & Medical CenterChristopher P Cannon, MD, Principal investigator, Harvard Clinical Research Organization and Cardiovascular Division Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02608099
- Sponsor's protocol ID
- CV185-373
- Acronym
- AEIOU
- Status last verified
- Mar 2020
- First submitted
- 9 Nov 2015
- Last updated
- 17 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 34674223Reynolds 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.
PubMed 29798783
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT02608099
- Acronym / sponsor ID
- AEIOU / CV185-373
- Conditions
- Atrial Fibrillation
- Keywords
- Atrial fibrillation, Non-valvular atrial fibrillation, Catheter ablation, Apixaban, Warfarin, Harvard Clinical Research Institute
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Baim Institute for Clinical ResearchUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Nov 2015
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 18 Nov 2015 (estimated)
- Results
- Posted 17 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interrupted apixaban | Active comparator | Drug: Interrupted apixabanApixaban 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 | Experimental | Drug: Uninterrupted apixabanApixaban 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed informed consent.
- >18 years of age.
- NVAF with planned catheter ablation treatment.
- Planned anticoagulant treatment for at least 1 month after the index procedure.
- Subject agrees to all required follow-up procedures and visits.
Key exclusion criteria (17 listed)
- History of significant bleeding diathesis or coagulopathy or inability to accept blood transfusions.
- Known hypersensitivity or contraindication to heparin or apixaban.
- Subjects with mechanical prosthetic heart valves.
- History of cerebrovascular accident or transient ischemic attach (TIA) within the last 6 months.
- Prior intracranial hemorrhage.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interrupted apixabanAlso: Interrupted EliquisApixaban 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 |
| Uninterrupted apixabanAlso: Uninterrupted EliquisIntervention 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. | Drug | Uninterrupted apixaban |
Primary outcome
Number of Patients With Clinically-Significant Bleeding
Time frame: Randomization to 1 month post catheter ablation
Clinically significant bleeding was defined as bleeding meeting Bleeding Academic Research Consortium (BARC) criteria type 2 or higher.
Number of Patients With Thrombotic Events
Time frame: Randomization to 1 month post catheter ablation
Thrombotic events were defined as a composite of non-hemorrhagic stroke and systemic thromboembolic events.
2 secondary outcomes
Number of Patients With Composite of Major Bleeding and Thrombotic Events
Time frame: Randomization to 1 month post catheter ablation
Number of Patients With Composite of Clinically Significant Bleeding and Thrombotic Events
Time frame: Randomization to 1 month post catheter ablation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34674223Bawazeer 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.
- Derived from this study: PubMed 29798783Reynolds 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.
Related trials for Atrial Fibrillation
Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Reynolds, MD, MSc principal investigator
Lahey Hospital & Medical Center
Christopher P Cannon, MD principal investigator
Harvard Clinical Research Organization and Cardiovascular Division Brigham and Women's Hospital
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Interrupted apixaban and Uninterrupted apixaban in people with Atrial Fibrillation, run by Baim Institute for Clinical Research at 19 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Clinically-Significant Bleeding (time frame: Randomization to 1 month post catheter ablation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02608099, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.