Atrial Fibrillation, Intracerebral Hemorrhage
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGNOAC
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.
DRUGAcetylsalicylic Acid
Acetylsalicylic acid 81 mg/day
Sponsors
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previous primary intracerebral hemorrhage * Atrial fibrillation (CHADS2 ≥ 2)
Exclusion criteria
* Non-stroke indication for antiplatelet or anticoagulant therapy * Recent intracerebral hemorrhage within 14 days * Platelet count less than 100,000/mm3 at enrollment or other bleeding diathesis * Prior symptomatic lobar intracerebral hemorrhage other than the qualifying event * Uncontrollable hypertension consistently above SBP/DBP of 160/100 mmHg * Known hypersensitivity to either ASA or NOACs * Inability to adhere to study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of ischemic stroke and recurrent intracerebral hemorrhage | Through study completion; average of 1 year | The composite of ischemic stroke and recurrent intracerebral hemorrhage |
| Recruitment rate | Through study completion; ~ 30 months | The mean number of patients randomized per site per year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Refusal rate | Through study completion; average of 1 year | Average number of eligible patients per site who refuse consent. |
| Retention rate | Through study completion; average of 1 year | Randomized patients who completed 6 months of follow-up on drug or died during trial participation. |
| Ischemic stroke | Through study completion; average of 1 year | Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke. |
| Intracerebral hemorrhage | Through study completion; average of 1 year | A neurologic deficit associated with an intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy. |
| Myocardial infarction | Through study completion; average of 1 year | 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. |
| All-cause mortality | Through study completion; average of 1 year | Persistent and irreversible absence of brain or brainstem function. |
| Major hemorrhage | Through study completion; average of 1 year | 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. |
| Intracranial hemorrhage | Through study completion; average of 1 year | 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. |
| Composite of all stroke, myocardial infarct, systemic thromboembolism or death | Through study completion; average of 1 year | Composite of all stroke, myocardial infarct, systemic thromboembolism or death |
| Modified Rankin Scale (mRS) | Through study completion; average of 1 year | Average mRS score |
| Montreal Cognitive Assessment (MOCA) | Through study completion; average of 1 year | Average MOCA score |
| Systemic thromboembolism | Through study completion; average of 1 year | Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage. |
| Fatal stroke | Through study completion; average of 1 year | Death that is attributable to an ischemic stroke or intracerebral hemorrhage. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Weighted net clinical benefit | Through study completion; average of 1 year | Weighted net clinical benefit factoring the impact of ischemic stroke, intracerebral hemorrhage, non-intracerebral intracranial hemorrhage, major extracranial hemorrhage and myocardial infarction on death and disability. |
Countries
Canada
Outcome results
None listed