Edoxaban for TIA and Acute Minor Stroke

Sponsor

Xijing Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02221102

Collaborator

(none)

3,700

Enrollment

Location

Arms

Duration (Months)

123.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ischemia Stroke Cerebral Infarction	Drug: Aspirin Drug: edoxaban Drug: placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2013

Anticipated Primary Completion Date :

Jun 1, 2015

Anticipated Study Completion Date :

Jun 1, 2016

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: aspirin

Receiving a 100-mg dose of aspirin and placebo edoxaban from day 1 to day 30

Drug: Aspirin

non-steroidal anti-inflammatory drugs

Other Names:

Acetylsalicylic acid

Drug: placebo

Experimental: edoxaban 30mg

Receiving a 30-mg dose of edoxaban and placebo aspirin from day 1 to day 30

Drug: edoxaban

orally active direct factor Xa inhibitor

Other Names:

DU176b

LIXIANA TABLETS

Drug: placebo

Experimental: edoxaban 60mg

Receiving a 60-mg dose of edoxaban and placebo aspirin from day 1 to day 30

Drug: edoxaban

orally active direct factor Xa inhibitor

Other Names:

DU176b

LIXIANA TABLETS

Drug: placebo

Outcome Measures

Primary Outcome Measures

percentage of patients with new stroke (ischemic or hemorrhage) [90 days]

Secondary Outcome Measures

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]
Total mortality [90 days]
Adverse events/severe adverse events reported by the investigators [90 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)