NOACs for Stroke Prevention in Patients With Atrial Fibrillation and Previous ICH (NASPAF-ICH)

• ClinicalTrials.gov Identifier: NCT02998905
• Recruitment Status: Completed
• First Posted: December 21, 2016
• Last Update Posted: March 20, 2020
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Ashkan Shoamanesh, Population Health Research Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Intracerebral Hemorrhage	Drug: NOAC; Drug: Acetylsalicylic Acid	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation and Previous Intracerebral Hemorrhage Study
• Actual Study Start Date: April 26, 2017
• Actual Primary Completion Date: October 31, 2019
• Actual Study Completion Date: February 18, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: NOAC; Apixaban or dabigatran or edoxaban or rivaroxaban	Drug: NOAC; 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.
Active Comparator: Acetylsalicylic Acid; Acetylsalicylic acid	Drug: Acetylsalicylic Acid; Acetylsalicylic acid 81 mg/day

Outcome Measures

Primary Outcome Measures :

1. Recruitment rate [ Time Frame: Through study completion; ~ 30 months ]
   The mean number of patients randomized per site per year.
2. Composite of ischemic stroke and recurrent intracerebral hemorrhage [ Time Frame: Through study completion; average of 1 year ]
   The composite of ischemic stroke and recurrent intracerebral hemorrhage

Secondary Outcome Measures :

1. Refusal rate [ Time Frame: Through study completion; average of 1 year ]
   Average number of eligible patients per site who refuse consent.
2. Retention rate [ Time Frame: Through study completion; average of 1 year ]
   Randomized patients who completed 6 months of follow-up on drug or died during trial participation.
3. Ischemic stroke [ Time Frame: Through study completion; average of 1 year ]
   Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.
4. Intracerebral hemorrhage [ Time Frame: 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.
5. Fatal stroke [ Time Frame: Through study completion; average of 1 year ]
   Death that is attributable to an ischemic stroke or intracerebral hemorrhage.
6. Myocardial infarction [ Time Frame: 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.
7. All-cause mortality [ Time Frame: Through study completion; average of 1 year ]
   Persistent and irreversible absence of brain or brainstem function.
8. Systemic thromboembolism [ Time Frame: Through study completion; average of 1 year ]
   Emboli to the arterial circulation excluding myocardial infarction, ischemic stroke or intracerebral hemorrhage.
9. Major hemorrhage [ Time Frame: 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.
10. Intracranial hemorrhage [ Time Frame: 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.
11. Composite of all stroke, myocardial infarct, systemic thromboembolism or death [ Time Frame: Through study completion; average of 1 year ]
    Composite of all stroke, myocardial infarct, systemic thromboembolism or death
12. Modified Rankin Scale (mRS) [ Time Frame: Through study completion; average of 1 year ]
    Average mRS score
13. Montreal Cognitive Assessment (MOCA) [ Time Frame: Through study completion; average of 1 year ]
    Average MOCA score

Other Outcome Measures:

1. Weighted net clinical benefit [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Foothills Medical Centre

Calgary, Alberta, Canada, T2N 4N1

University of Alberta Hospital

Edmonton, Alberta, Canada

Canada, British Columbia

Vancouver Coastal Health Research Institute

Vancouver, British Columbia, Canada, V6T 2B5

Canada, Ontario

Hamilton Health Sciences

Hamilton, Ontario, Canada, L9G1J8

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

Canada, Quebec

Hopital Notre-Dame du CHUM

Montréal, Quebec, Canada

Sponsors and Collaborators

Population Health Research Institute

Investigators

• Principal Investigator: Ashkan Shoamanesh, MD FRCPC; Population Health Research Institute

More Information

• Responsible Party: Ashkan Shoamanesh, Assistant Professor of Medicine (Neurology), Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT02998905
• Other Study ID Numbers: NASPAF-ICH
• First Posted: December 21, 2016
• Last Update Posted: March 20, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cerebral Hemorrhage; Atrial Fibrillation; Hemorrhage; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics