Edoxaban for TIA and Acute Minor Stroke

Treatment of Edoxaban Versus Aspirin for Non-disabling Cerebrovascular Events: Rationale, Objectives, and Design

Transient ischemic attack (TIA) or minor ischemic stroke has a high risk of early recurrent stroke. As the golden standard, aspirin effect modestly on acute ischemic stroke, and slightly increase the risk of intracerebral hemorrhage. Recently, edoxaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants, while carrying significantly less risk of intracranial hemorrhage.

This trial is a randomized, double-blind, multicenter, controlled clinical trial in China. The investigators will assess the hypothesis that a 30-days edoxaban regimen is superior to aspirin alone for the treatment of high-risk patients with acute nondisabling cerebrovascular event.

Study Overview

• Status: Unknown
• Conditions: Ischemia; Stroke; Cerebral Infarction
• Intervention / Treatment: Drug: placebo; Drug: Aspirin; Drug: edoxaban

• Study Type: Interventional
• Enrollment (Anticipated): 3700
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult subjects (male or female ≥18 years old)
• Acute nondisabling ischemic stroke (NIHSS ≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
• TIA (neurologic deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with investigational medication within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
• Informed consent signed

Exclusion Criteria:

• Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major nonischemic brain disease, on baseline head CT or MRI scan
• mRS score >2 at randomization (premorbid historical assessment)
• NIHSS ≥4 at randomization
• Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state)
• Contraindication to investigational medications
• Thrombolysis for ischemic stroke within preceding 7 days
• History of intracranial hemorrhage
• Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anticoagulation
• Gastrointestinal bleed or major surgery within 3 months
• Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
• TIA or minor stroke induced by angiography or surgery
• Severe noncardiovascular comorbidity with life expectancy <3 months
• Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test result
• Severe renal failure, defined as Glomerular Filtration Rate (GFR) <30 ml/min -Severe hepatic insufficiency (Child-Pugh score B to C)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: aspirin; Receiving a 100-mg dose of aspirin and placebo edoxaban from day 1 to day 30	Drug: placebo; Drug: Aspirin; non-steroidal anti-inflammatory drugs; Other Names: Acetylsalicylic acid
Experimental: edoxaban 30mg; Receiving a 30-mg dose of edoxaban and placebo aspirin from day 1 to day 30	Drug: placebo; Drug: edoxaban; orally active direct factor Xa inhibitor; Other Names: DU176b; LIXIANA TABLETS
Experimental: edoxaban 60mg; Receiving a 60-mg dose of edoxaban and placebo aspirin from day 1 to day 30	Drug: placebo; Drug: edoxaban; orally active direct factor Xa inhibitor; Other Names: DU176b; LIXIANA TABLETS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
percentage of patients with new stroke (ischemic or hemorrhage)	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Total mortality	90 days
Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)	30 days
mRS score changes (continuous) and dichotomized at percentage with score 0 to 2 versus 3 to 6	30 days and 90 days
Changes in NIHSS scores	90 days
moderate to severe bleeding events	90 days
Adverse events/severe adverse events reported by the investigators	90 days

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Gang Zhao, M.D., Xijing hostipal

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: August 18, 2014
• First Submitted That Met QC Criteria: August 18, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Estimate): August 20, 2014
• Last Update Submitted That Met QC Criteria: August 18, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: aspirin; TIA; edoxaban; new oral anticoagulant; acute minor ischemic stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Brain Infarction; Infarction; Stroke; Ischemia; Cerebral Infarction; 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; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Edoxaban
• Other Study ID Numbers: Xijing-Edoxaban