To determine the feasibility of a controlled trial examining the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with ASA for stroke prevention in patients with a high-risk of atrial fibrillation and previous intracerebral hemorrhage.
The NASPAF-ICH study is an open-label, randomized, controlled, phase II study that will assess the feasibility of a controlled trial examining the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with acetylsalicylic acid (ASA) for stroke prevention in patients with high-risk atrial fibrillation and previous intracerebral hemorrhage, as well as provide evidence of efficacy and safety for planning of a phase III trial. Recruitment will occur at 10 high-volume stroke research centres across Canada over 2 years, at which 100 adult patients with high-risk atrial fibrillation (CHADS2 ≥2) and previous spontaneous or traumatic ICH (intraparenchymal or intraventricular hemorrhage while on or off anticoagulation) will be randomly assigned to receive a NOAC (particular agent at the discretion of the local investigator) or ASA 81 mg per day. Patients will be followed for a mean of 1 year to a common end-study date. The feasibility of recruitment will also be tested. The investigators estimate that five patients per year per centre can be recruited.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
30
Apixaban or dabigatran or edoxaban or rivaroxaban at recommended dosing for stroke prevention in atrial fibrillation. The particular agent is at the discretion of the local investigator.
Acetylsalicylic acid 81 mg/day
Foothills Medical Centre
Calgary, Alberta, Canada
University of Alberta Hospital
Edmonton, Alberta, Canada
Vancouver Coastal Health Research Institute
Vancouver, British Columbia, Canada
Hamilton Health Sciences
Hamilton, Ontario, Canada
Recruitment rate
The mean number of patients randomized per site per year.
Time frame: Through study completion; ~ 30 months
Composite of ischemic stroke and recurrent intracerebral hemorrhage
The composite of ischemic stroke and recurrent intracerebral hemorrhage
Time frame: Through study completion; average of 1 year
Refusal rate
Average number of eligible patients per site who refuse consent.
Time frame: Through study completion; average of 1 year
Retention rate
Randomized patients who completed 6 months of follow-up on drug or died during trial participation.
Time frame: Through study completion; average of 1 year
Ischemic stroke
Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.
Time frame: Through study completion; average of 1 year
Intracerebral hemorrhage
A neurologic deficit associated with an intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.
Time frame: Through study completion; average of 1 year
Fatal stroke
Death that is attributable to an ischemic stroke or intracerebral hemorrhage.
Time frame: Through study completion; average of 1 year
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London Health Sciences Centre - University Hospital
London, Ontario, Canada
The Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Toronto Western Hospital
Toronto, Ontario, Canada
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada
Myocardial infarction
Defined by presence of at least one of the following a compatible clinical history and characteristic serum enzymes changes with or without electrocardiographic abnormalities; clinical history and serial ST-segment and T-wave changes which are specifically located with respect to the electrocardiographic leads accompanied by elevation of CPK-MB isoenzyme or troponin in serum; the development of large Q-waves on electrocardiography associated with changes in the ST-segments and T-waves in specific and appropriate leads which indicate the location of the infarct, even in the absence of symptoms or abnormalities in serum enzymes; development of discrete, segmental left ventricular systolic wall motion abnormality concurrent with compatible clinical history, electrocardiographic changes or serum enzyme abnormalities; or histopathological evidence of subacute myocardial necrosis.
Time frame: Through study completion; average of 1 year
All-cause mortality
Persistent and irreversible absence of brain or brainstem function.
Time frame: Through study completion; average of 1 year
Systemic thromboembolism
Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage.
Time frame: Through study completion; average of 1 year
Major hemorrhage
Bleeding accompanied by one or more of the following - a decrease in the hemoglobin level of ≥20 g per liter over a 24-hour period, transfusion of ≥2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding.
Time frame: Through study completion; average of 1 year
Intracranial hemorrhage
Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.
Time frame: Through study completion; average of 1 year
Composite of all stroke, myocardial infarct, systemic thromboembolism or death
Composite of all stroke, myocardial infarct, systemic thromboembolism or death
Time frame: Through study completion; average of 1 year
Modified Rankin Scale (mRS)
Average mRS score
Time frame: Through study completion; average of 1 year
Montreal Cognitive Assessment (MOCA)
Average MOCA score
Time frame: Through study completion; average of 1 year