NOACs for Stroke Prevention in Patients With Atrial Fibrillation and Previous ICH

Study Overview
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Brief Summary
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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
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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.

Official Title
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Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation and Previous Intracerebral Hemorrhage Study

Conditions
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Atrial Fibrillation, Intracerebral Hemorrhage

Intervention / Treatment
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* Drug: NOAC
* Drug: Acetylsalicylic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOAC<br>Apixaban or dabigatran or edoxaban or rivaroxaban | Drug: NOAC<br>* 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.<br>|
| Active Comparator: Acetylsalicylic Acid<br>Acetylsalicylic acid | Drug: Acetylsalicylic Acid<br>* Acetylsalicylic acid 81 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | The mean number of patients randomized per site per year. | Through study completion;   30 months | 
| Composite of ischemic stroke and recurrent intracerebral hemorrhage | The composite of ischemic stroke and recurrent intracerebral hemorrhage | Through study completion; average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Refusal rate | Average number of eligible patients per site who refuse consent. | 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. | 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. | 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. | Through study completion; average of 1 year | 
| Fatal stroke | Death that is attributable to an ischemic stroke or intracerebral hemorrhage. | Through study completion; average of 1 year | 
| 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. | Through study completion; average of 1 year | 
| All-cause mortality | Persistent and irreversible absence of brain or brainstem function. | Through study completion; average of 1 year | 
| Systemic thromboembolism | Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage. | 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. | 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. | 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 | Through study completion; average of 1 year | 
| Modified Rankin Scale (mRS) | Average mRS score | Through study completion; average of 1 year | 
| Montreal Cognitive Assessment (MOCA) | Average MOCA score | Through study completion; average of 1 year |