Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation



Status:Recruiting
Conditions:Atrial Fibrillation, Cardiology, Neurology
Therapuetic Areas:Cardiology / Vascular Diseases, Neurology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:May 2015
End Date:July 2019
Contact:Heather Beresh, M.Sc
Email:heather.beresh@phri.ca
Phone:905-527-4322

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This study aims to determine if treatment with apixaban, compared with aspirin, will reduce
the risk of ischemic stroke and systemic embolism in patients with device-detected
sub-clinical atrial fibrillation and additional risk factors for stroke.

Device-detected sub-clinical atrial fibrillation (SCAF) is a new disorder that has been
recognized since the availability of implantable devices capable of long term continuous
heart rhythm monitoring. It is characterized by one or more runs of rapid atrial arrhythmia
detected by the device without symptoms and without any clinical atrial fibrillation (AF)
detected by the usual methods, (i.e. electrocardiogram, Holter monitor, etc.). In the ASSERT
trial, SCAF was detected by a pacemaker or implantable cardioverter defibrillator (ICD) in
nearly 40% of patients during 2 and a half years of follow up. The presence of SCAF
increased stroke risk by 2.5-fold (1). The risk of stroke or systemic embolism among
patients with SCAF and a CHADS2 score ≥ 4 was 2.75% per year. Oral anticoagulation is
effective and safe for stroke prevention in patients with clinical atrial fibrillation, but
it is unknown if the same risk benefit ratio exists for anticoagulation therapy in patients
with SCAF (2;3). SCAF differs from clinical AF in being of shorter duration, being
asymptomatic, and often have a more regular rhythm in the right atrium where it is typically
detected. Data ASSERT suggest that the increase in stroke risk with SCAF may be less than
the increase with clinical AF. Therefore opinion leaders have written that the role of oral
anticoagulation for the treatment of SCAF is uncertain and that randomized trials of
anticoagulation are needed (4;5). Recent surveys of pacemaker clinic practice indicate that
only 25% of patients with SCAF are treated with oral anticoagulation (6;7). Thus there is
clinical equipoise for a trial of oral anticoagulation compared to aspirin in higher risk
patients with SCAF.

Apixaban is a Factor Xa inhibitor that is an effective and safe anticoagulant. It has been
shown to have an excellent risk benefit profile for stroke prevention in clinical AF (14,
15). It is highly suitable to test if oral anticoagulation therapy will reduce the risk of
stroke or systemic embolism in SCAF.

Patients will be randomized double-blind to receive apixaban or aspirin. Apixaban dose will
be 5 mg twice daily (2.5 mg twice daily if 2 or more of: age > 80, weight ≤ 60 kg or serum
creatinine ≥ 133 mmol/L). Those assigned to aspirin will receive a dose of 81 mg daily. The
study will be event driven and will continue until 248 patients have experienced a primary
outcome event.

Inclusion Criteria:

1. Permanent pacemaker or defibrillator (with or without resynchronization) or
insertable cardiac monitor capable of detecting SCAF

2. At least one episode of SCAF ≥ 6 minutes in duration (Atrial rate > 175/min if an
atrial lead is present), but no single episode > 24 hours in duration. SCAF requires
electrogram confirmation (at least one episode) unless ≥ 6 hours in duration

3. Age > 18 years

4. CHA2DS2-VASc score of ≥ 4

Exclusion Criteria:

1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry,
Holter) lasting ≥ 6 minutes, with or without clinical symptoms

2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other
condition requiring treatment with an anticoagulant

3. Contra-indication to apixaban or aspirin:

1. Allergy to aspirin or apixaban

2. Severe renal insufficiency (creatinine clearance must be calculated in all
patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or
a calculated creatinine clearance < 25 ml/min is excluded)

3. Serious bleeding in the last 6 months or at high risk of bleeding (this
includes, but is not limited to: prior intracranial hemorrhage, active peptic
ulcer disease, platelet count < 50,000/mm3 or hemoglobin < 10 g/dL, recent
stroke within past 10 days, documented hemorrhagic tendencies or blood
dyscrasias)

4. Moderate to severe hepatic impairment

5. Ongoing need for combination therapy with aspirin and clopidogrel (or other
combination of two platelet inhibitors)

6. Meets criteria for requiring lower dose of apixaban AND also has ongoing need
for strong inhibitors of CYP 3A4 or P-glycoprotein (e.g., ketoconazole,
itraconazole, ritonavir or clarithromycin)

7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g.,
rifampin, carbamazepine, phenytoin, St. John's wort)

4. Received an investigational drug in the past 30 days

5. Participants considered by the investigator to be unsuitable for the study for any of
the following reasons:

1. Not agreeable for treatment with either aspirin or apixaban or anticipated to
have poor compliance on study drug treatment

2. Unwilling to attend study follow-up visits

3. Life expectancy less than the expected duration of the trial2 years due to
concomitant disease

6. Women who are pregnant, breast-feeding or of child-bearing potential without an
acceptable form of contraception in place (sterilization, hormonal contraceptives,
intrauterine device, barrier methods or abstinence)
We found this trial at
16
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Columbia, Missouri 65212
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30 Prospect Ave
Hackensack, New Jersey 07601
(201) 996-2000
Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
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Hershey, Pennsylvania 17033
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Kalispell, Montana 59901
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Mesa, Arizona 85206
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Plantation, Florida 33317
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Raleigh, North Carolina 27610
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St. Louis, Missouri 63136
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