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

Phase 2
Completed
Conditions
Atrial Fibrillation
Intracerebral Hemorrhage
Interventions
Registration Number
NCT02998905
Lead Sponsor
Population Health Research Institute
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NOACNOACApixaban or dabigatran or edoxaban or rivaroxaban
Acetylsalicylic AcidAcetylsalicylic AcidAcetylsalicylic acid
Primary Outcome Measures
NameTimeMethod
Recruitment rateThrough study completion; ~ 30 months

The mean number of patients randomized per site per year.

Composite of ischemic stroke and recurrent intracerebral hemorrhageThrough study completion; average of 1 year

The composite of ischemic stroke and recurrent intracerebral hemorrhage

Secondary Outcome Measures
NameTimeMethod
Retention rateThrough study completion; average of 1 year

Randomized patients who completed 6 months of follow-up on drug or died during trial participation.

Major hemorrhageThrough 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.

Montreal Cognitive Assessment (MOCA)Through study completion; average of 1 year

Average MOCA score

Ischemic strokeThrough study completion; average of 1 year

Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.

Fatal strokeThrough study completion; average of 1 year

Death that is attributable to an ischemic stroke or intracerebral hemorrhage.

Myocardial infarctionThrough 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 mortalityThrough study completion; average of 1 year

Persistent and irreversible absence of brain or brainstem function.

Intracranial hemorrhageThrough 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.

Refusal rateThrough study completion; average of 1 year

Average number of eligible patients per site who refuse consent.

Intracerebral hemorrhageThrough 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.

Systemic thromboembolismThrough study completion; average of 1 year

Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage.

Composite of all stroke, myocardial infarct, systemic thromboembolism or deathThrough 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

Trial Locations

Locations (9)

Foothills Medical Centre

🇨🇦

Calgary, Alberta, Canada

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

Vancouver Coastal Health Research Institute

🇨🇦

Vancouver, British Columbia, Canada

Hopital Notre-Dame du CHUM

🇨🇦

Montréal, Quebec, Canada

London Health Sciences Centre - University Hospital

🇨🇦

London, Ontario, Canada

Hamilton Health Sciences

🇨🇦

Hamilton, Ontario, Canada

The Ottawa Hospital Research Institute

🇨🇦

Ottawa, Ontario, Canada

Toronto Western Hospital

🇨🇦

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

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