To determine if the use of apixaban in patients with SCAF will reduce the incidence of stroke and systemic embolism compared to aspirin.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy: Composite of stroke (including transient ischemic attack (TIA) with
evidence of cerebral infarction on diffusion-weighted MRI) and systemic embolism
Safety: Major bleeding as defined by the ISTH criteria
Secondary outcome
* Ischemic stroke
* Myocardial infarction
* Vascular death
* Total death (vascular and non-vascular)
* Composite of stroke, myocardial infarction, systemic embolism and total death
* Composite of stroke, myocardial infarction, systemic embolism, total death
and major bleeding
Background summary
Device-detected sub-clinical atrial fibrillation (SCAF) 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 was associated with increased stroke risk (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).
Very few patients with SCAF were enrolled in the trials of anticoagulation in
patients with AF. SCAF differs from clinical AF in being of shorter duration
and, being asymptomatic. Data from ASSERT suggest that the increase in stroke
risk with SCAF may be less than the increase with clinical AF. Thus although
SCAF is a variant of AF, 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.
Study objective
To determine if the use of apixaban in patients with SCAF will reduce the
incidence of stroke and systemic embolism compared to aspirin.
Study design
Prospective, randomized, parallel group, double-blind trial.
Eligible and consenting participants will be randomized, will have an
interrogation of the implanted device, an electrocardiogram, a laboratory
evaluation of serum creatinine and medical history obtained at the enrollment
visit. Participants will return for follow-up visits at 30 days, and then every
6 months, when they will be assessed for outcome events and with questions to
verify stroke-free status. The study will be event driven and will continue
until 248 primary events have occurred, which is anticipated to occur when
average patient follow-up is approximately 36 months.
Intervention
The Double-dummy approach will be used to achieve double-blind treatment.
Aspirin Arm will receive:
Active aspirin at a dose of 81mg once daily; and placebo-apixaban
Apixaban Arm will receive:
Active apixaban at a dose of 5 mg twice daily (2.5 mg twice daily if 2 or more
of: age >= 80, weight <= 60 kg or serum creatinine >= 133 µmol/L or >= 1.5 mg/dL);
and placebo-aspirin
Study burden and risks
The time burden for the patient is minimal. The IP can cause side effects. The
most common effects are bleeding, bruising, vomiting and blood in stool or
urine. For other risks of the IP I refer you to the SPC and the ICF. The risks
with regards to blood draws are small risks such as bruising, infection or
swelling at the site of needle entry. There are no risks associated with the
reading of the ICD or ECG.
Birge Street 30
Hamilton ON L8L 0A6
CA
Birge Street 30
Hamilton ON L8L 0A6
CA
Listed location countries
Age
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 device-detected SCAF >= 6 minutes in duration but no
single episode > 24 hours in duration at any time prior to enrollment. Any
atrial high rate episode with average > 175 beats/min will be considered as
SCAF. No distinction will be made between atrial fibrillation and atrial
flutter. SCAF requires electrogram confirmation (at least one episode) unless >=
6 hours in duration
3. Age > 55 years
4. Risk Factor(s) for Stroke: Previous stroke, TIA or systemic arterial
embolism OR Age at least 75 OR Age 65-74 with at least 2 other risk factors OR
Age 55-64 with at least 3 other risk factors
Other risk factors are: hypertension, CHF, diabetes, vascular disease (i.e.
CAD, PAD or Aortic Plaque) and female
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:
a. Allergy to aspirin or apixaban
b. 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)
c. 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, clinically significant thrombocytopenia or anemia, recent stroke
within past 10 days, documented hemorrhagic tendencies or blood dyscrasias)
d. Moderate to severe hepatic impairment
e. Ongoing need for combination therapy with aspirin and clopidogrel (or other
combination of two platelet inhibitors)
f. 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)
g. 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:
* Not agreeable for treatment with either aspirin or apixaban or anticipated to
have poor compliance on study drug treatment
* Unwilling to attend study follow-up visits
* Life expectancy less than 2 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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001397-33-NL |
| ClinicalTrials.gov | NCT01938248 |
| CCMO | NL51481.028.15 |