Testing a New Treatment Strategy to Improve Secondary Stroke Prevention for Older Adults: The STROKE75+ Trial

NCT07454707 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: STROKE75+
• Study Type: interventional
• Target: 1,204
• Locations: 0 countries
• Sites: N/A

Brief Summary

The overall aim of this research is to improve secondary stroke prevention for older patients with stroke. In current practice, patients with stroke are often prescribed antiplatelet therapy with either aspirin or clopidogrel to help prevent recurrent strokes. However, an antiplatelet medication may not be effective enough for some patients. A promising new treatment strategy to enhance stroke prevention involves a very low dose of an anticoagulant (anti-clotting medication) added to the standard antiplatelet therapy. In a previous study, this approach cut stroke risk in half among patients with heart/vascular disease, but it has not yet been formally tested in an older stroke population. The STROKE75+ trial is now being conducted to carefully evaluate the potential benefits and potential risks of this type of treatment strategy for secondary stroke prevention. The medication being tested in the STROKE75+ trial is a commonly used anticoagulant called edoxaban -- at a reduced dose of 15mg once daily (one-quarter of its full dose) to minimize the chance of bleeding. In previous research, edoxaban 15mg daily has been shown to be safe and effective for preventing strokes in patients with atrial fibrillation, but it has not been studied in stroke patients without atrial fibrillation. This trial aims to answer the following questions:

1. 1.Does the addition of edoxaban 15mg once a day to standard antiplatelet therapy reduce the risk of recurrent strokes more than standard antiplatelet therapy alone?
2. 2.Does the addition of edoxaban 15mg daily reduce the risk of severe (disabling) strokes, dementia, or heart attacks?
3. 3.What is the incidence of bleeding with/without edoxaban 15mg daily?

Conditions

Stroke, Ischemic

Keywords

Stroke; Secondary Stroke Prevention; Anticoagulation; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (2)

• Rate of new strokes (fatal or non-fatal)

  The primary efficacy outcome is the rate of new strokes (fatal or non-fatal) - defined as a composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or unknown type of stroke.

  From randomization to the end of study (approx. 2-4 years)

• Rate of ISTH major bleeding

  The primary safety outcome is the rate of ISTH major bleeding, defined as: * Fatal bleeding; and/or * Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular (excludes conjunctival), retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome \[note that bleeding in a critical area or organ must be associated with a symptomatic clinical presentation related to the bleeding in order for this criterion to be met according to the ISTH definition\]; and/or * Bleeding causing a fall in hemoglobin level of 20 g/L or more, or leading to transfusion of two or more units of whole blood or red cells. Note: To qualify as a major bleed, it must be symptomatic, clinically overt bleeding (either visible bleeding or bleeding documented by imaging). Asymptomatic bleeding or a hemoglobin drop without evidence of bleeding is not classified as a major bleed.

  From randomization to the end of study (approx. 2-4 years)

Secondary Outcomes (14)

• Rates of the secondary efficacy outcomes

  From randomization to the end of study (approx. 2-4 years)

• Rates of the secondary safety outcomes

  From randomization to the end of study (approx. 2-4 years)

• Secondary Efficacy Outcome-modified Rankin Scale (mRS)

  From randomization to the end of study (approx. 2-4 years)

• Secondary Efficacy Outcome- Poststroke modified Rankin Scale (mRS) score

  From randomization to the end of study (approx. 2-4 years)]

• Secondary Efficacy Outcome- Recurrent ischemic strokes

  From randomization to the end of study (approx. 2-4 years)

Other Outcomes (6)

• Net benefit outcome: rate of stroke or major bleeding

  From randomization to the end of study (approx. 2-4 years)

• Other Outcomes-new atrial fibrillation diagnosis

  From randomization to the end of study (approx. 2-4 years)

• Net benefit outcome: rate of stroke, MI, CV death, or major bleeding

  From randomization to the end of study (approx. 2-4 years)

Study Arms (2)

Intervention Group (combination therapy group)

EXPERIMENTAL

Open-label edoxaban 15 mg po once daily added to standard-care single antiplatelet therapy (either aspirin 81 mg \[or 80 mg\] po once daily or clopidogrel 75 mg po once daily; the choice of antiplatelet agent is at the discretion of the treating physician)

Drug: Edoxaban 15 mg; Drug: Aspirin or clopidogrel

Control Group (standard-care group)

ACTIVE COMPARATOR

Standard-care single antiplatelet therapy (either aspirin 81 mg \[or 80 mg\] po once daily or clopidogrel 75 mg po once daily; the choice of antiplatelet agent is at the discretion of the treating physician)

Drug: Aspirin or clopidogrel

Interventions

Edoxaban 15 mg DRUG

Edoxaban is a once-daily oral tablet. It can be taken with or without food. Edoxaban is widely used worldwide for the prevention of stroke in patients with atrial fibrillation, treatment of venous thromboembolism (DVT/PE), and prevention of recurrent DVT/PE. It works by inhibiting a coagulation protein called Factor Xa to reduce thrombin generation and prevent blood clots. For this trial, the dose of edoxaban chosen is 15 mg once a day (which is one-quarter of the full dose) to minimize the chance of bleeding problems. The 15 mg dose of edoxaban has been shown to be safe and effective for preventing strokes in patients with atrial fibrillation, but it has not yet been studied for stroke prevention in patients without atrial fibrillation.

Intervention Group (combination therapy group)

Aspirin or clopidogrel DRUG

Standard-care single antiplatelet therapy (either aspirin 81 mg \[or 80 mg\] po once daily or clopidogrel 75 mg po once daily; the choice of antiplatelet agent is at the discretion of the treating physician)

Control Group (standard-care group); Intervention Group (combination therapy group)

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥75 years on the day of informed consent.
• Diagnosis of an acute ischemic stroke within the preceding 12 months, which was clinically symptomatic and confirmed by neuroimaging (CT or MRI), and for which the treatment plan is single antiplatelet therapy with either aspirin 81 mg daily (80 mg daily is permitted) or clopidogrel (75 mg daily) for long-term secondary stroke prevention.
• \[Note: The qualifying stroke event can be a clinical transient ischemic attack if there was neuroimaging evidence of acute ischemia/infarction on brain imaging. A clinically symptomatic acute intracranial vessel occlusion on angiography that recanalized without infarction is eligible for enrolment.\]
• The patient has had ECG monitoring after the qualifying stroke event (Holter, telemetry, or other continuous ECG monitoring device) totalling at least 24 hours and with no episodes of atrial fibrillation (or atrial flutter) ≥6 minutes AND a routine 12-lead ECG within 90 days before randomization shows sinus rhythm (no atrial fibrillation or atrial flutter).
• Written informed consent from participant or legally authorized representative.

You may not qualify if:

• Diagnosis of atrial fibrillation or atrial flutter (AF) documented in the patient's medical history or examination; any AF on a 12-lead ECG; or any episode of AF ≥6 minutes on a Holter or other continuous ECG monitor.
• Any of the following 'major-risk' cardiac sources of embolism based on the patient's medical history and post-stroke echocardiography (transthoracic or transesophageal) or other cardiac imaging within the past 12 months: mechanical heart valve; intracardiac thrombus; atrial myxoma or other cardiac tumor; recent (\<4 weeks) myocardial infarction; or valvular vegetations or diagnosed/suspected infective endocarditis.
• The patient has a medical requirement for chronic anticoagulant therapy or dual antiplatelet therapy, or dual or triple antithrombotic therapy (e.g. recent acute coronary syndrome or vascular stenting procedure, venous thromboembolism (DVT/PE), hypercoagulable state) or chronic nonsteroidal anti-inflammatory drug (NSAID) therapy.
• The qualifying stroke etiology is attributed to vasculitis, arterial dissection, migraine, vasospasm, drug abuse, infective endocarditis, antiphospholipid antibody syndrome or other high-risk thrombophilia; Moya Moya; CADASIL or other genetic cause; other infectious or inflammatory cause; or an iatrogenic/procedure-related cause (e.g. post-operative stroke).
• History of gastrointestinal bleeding or another major bleeding event within the past 12 months; active or recent spontaneous non-trivial bleeding (within the past 30 days); unresolved peptic ulcer; or considered by the enrolling investigator to be at high risk for serious bleeding for any reason.
• Hepatic disease associated with coagulopathy; acute hepatitis; chronic active hepatitis; severe hepatic disease (Child-Pugh class C); or cirrhosis.
• Receiving hemodialysis or peritoneal dialysis, or dialysis is planned within the next 12 months.
• History of CT-detected intracranial hemorrhage (intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma).
• Uncontrolled hypertension (BP persistently \>160 mmHg systolic or \>100 mmHg diastolic) within the past 7 days before informed consent.
• calculated creatinine clearance \<30 mL/min (Cockroft Gault);
• platelet count \<100 x 109/L;
• hemoglobin \<100 g/L;
• INR \>1.3
• Body weight \<45 kg.
• The patient is receiving any of the following medications and is unable to stop or switch before randomization:

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

edoxaban; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

David Gladstone, BSc, MD, PhD, FRCPC

CONTACT

+1 416-480-4226; STROKE75trial@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Central Telephone Assessors; Central Adjudication Committee; Senior Study Statistician; Principal Investigator, Co-PIs, Steering Committee
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible male and female patients aged 75 years or older with an ischemic stroke in the past 12 months, and no established indication for anticoagulation, are randomized to receive edoxaban 15 mg po once daily added to their standard-care single antiplatelet therapy vs. standard-care single antiplatelet therapy.

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: March 6, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 6, 2026

Record last verified: 2026-02