Ischemic Stroke, TIA
Conditions
Keywords
apixaban, clopidogrel, aspirin, new oral anticoagulant, TIA, acute minor ischemic stroke
Brief summary
Nondisabling cerebrovascular events represent the largest group of cerebrovascular disease with a high risk of recurrent stroke. A recent trial indicated that clopidogrel and aspirin treatment reduced the risk of recurrent stroke and was not associated with increased hemorrhage events, compared with aspirin monotherapy. Apixaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants with less risk of bleeding events. To estimate whether apixaban is beneficial for acute TIA or minor stroke, a randomized, double-blind, multicenter, controlled clinical trial has been designed. The investigators will assess the hypothesis that a 21-days apixaban regimen is superior to clopidogrel and aspirin dual-therapy for the treatment of high-risk patients with acute nondisabling cerebrovascular event.
Detailed description
The ADANCE study is a randomized, double-blind clinical trial with a target enrollment of 3,000 Chinese patients. Two subtypes of patients will be enrolled: I, acute disabling ischemic stroke (\<24 hours of symptoms onset); II, acute TIA (\<24 hours of symptoms onset). Patients will be randomized into 3 groups: Ⅰ Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily. Ⅱ Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21. Ⅲ Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21. From day 22 to 3 months, all patients will receive 75-mg dose of clopidogrel long-term antiplatelet therapy. The primary efficacy end point is percentage of patients with new stroke (ischemic or hemorrhage) at 90 days.
Interventions
DRUGAspirin
a non-steroidal anti-inflammatory drug
DRUGApixaban
orally active direct factor Xa inhibitor
DRUGClopidogrel
an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor
DRUGplacebo
Sponsors
Xijing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| percentage of patients with new stroke (ischemic or hemorrhage) | 90 days |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) | 30 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 |
Countries
China
Contacts
Primary ContactXuedong Liu, M.D.
Outcome results
None listed