Clinical trial NCT01924325: Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in Acute Non-disabling Cerebrovascular Events
Official title: Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in High-risk Patients With Acute Non-disabling Cerebrovascular Events (ADANCE): Rationale, Objectives, and Design
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Ischemic Stroke
TIA
Keywords: apixaban
clopidogrel
aspirin
new oral anticoagulant
TIA
acute minor ischemic stroke
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2013-08-16
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: percentage of patients with new stroke (ischemic or hemorrhage)
timeFrame: 90 days
Secondary outcomes:
measure: Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)
timeFrame: 30 days
measure: Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)
timeFrame: 30 days and 90 days
measure: Changes in NIHSS scores
timeFrame: 90 days
measure: moderate to severe bleeding events
timeFrame: 90 days
measure: Total mortality
timeFrame: 90 days
measure: Adverse events/severe adverse events reported by the investigators
timeFrame: 90 days
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
Study officials:
affiliation: Neurology Department,Xijing Hospital
name: Gang Zhao, M.D.
role: PRINCIPAL_INVESTIGATOR
References: