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

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Intracerebral Hemorrhage
• Intervention / Treatment: Drug: NOAC; Drug: Acetylsalicylic Acid

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Vancouver Coastal Health Research Institute
  • Ontario
    • Hamilton, Ontario, Canada, L9G1J8
      • Hamilton Health Sciences
    • London, Ontario, Canada
      • London Health Sciences Centre - University Hospital
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • Toronto Western Hospital
  • Quebec
    • Montréal, Quebec, Canada
      • Hopital Notre-Dame du CHUM

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted net clinical benefit	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.	Through study completion; average of 1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2017
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): February 18, 2020

Study Registration Dates

• First Submitted: November 25, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No