Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in Acute Non-disabling Cerebrovascular Events

Overview[ - collapse ][ - ]

Purpose 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.
ConditionIschemic Stroke
TIA
InterventionDrug: Apixaban
Drug: Clopidogrel
Drug: Aspirin
Drug: placebo
PhasePhase 2/Phase 3
SponsorXijing Hospital
Responsible PartyXijing Hospital
ClinicalTrials.gov IdentifierNCT01924325
First ReceivedAugust 13, 2013
Last UpdatedAugust 13, 2013
Last verifiedAugust 2013

Tracking Information[ + expand ][ + ]

First Received DateAugust 13, 2013
Last Updated DateAugust 13, 2013
Start DateJanuary 2014
Estimated Primary Completion DateJuly 2016
Current Primary Outcome Measurespercentage of patients with new stroke (ischemic or hemorrhage) [Time Frame: 90 days] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) [Time Frame: 30 days] [Designated as safety issue: Yes]
  • Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) [Time Frame: 30 days and 90 days] [Designated as safety issue: No]
  • Changes in NIHSS scores [Time Frame: 90 days] [Designated as safety issue: No]
  • moderate to severe bleeding events [Time Frame: 90 days] [Designated as safety issue: No]
  • Total mortality [Time Frame: 90 days] [Designated as safety issue: Yes]
  • Adverse events/severe adverse events reported by the investigators [Time Frame: 90 days] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitleApixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in Acute Non-disabling Cerebrovascular Events
Official TitleApixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in High-risk Patients With Acute Non-disabling Cerebrovascular Events (ADANCE): Rationale, Objectives, and Design
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.
Study TypeInterventional
Study PhasePhase 2/Phase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Condition
  • Ischemic Stroke
  • TIA
InterventionDrug: Apixaban
orally active direct factor Xa inhibitor
Other Names:
  • Eliquis
  • BMS-562247
  • BMS-562247-01
Drug: Clopidogrel
an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor
Other Names:
  • Plavix
  • Clopivid
Drug: Aspirin
a non-steroidal anti-inflammatory drug
Other Names:
Acetylsalicylic acidDrug: placebo
Study Arm (s)
  • Active Comparator: Dual-antiplatelet Therapy
    Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily
  • Experimental: Apixaban 2.5mg
    Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21
  • Experimental: Apixaban 5mg
    Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21

Recruitment Information[ + expand ][ + ]

Recruitment StatusNot yet recruiting
Estimated Enrollment10000
Estimated Completion DateJuly 2016
Estimated Primary Completion DateDecember 2015
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)
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Xuedong Liu, M.D.
+86 029 84775055
liuxued@fmmu.edu.cn
Location CountriesChina

Administrative Information[ + expand ][ + ]

NCT Number NCT01924325
Other Study ID NumbersXijing-ADANCE
Has Data Monitoring CommitteeYes
Information Provided ByXijing Hospital
Study SponsorXijing Hospital
CollaboratorsNot Provided
Investigators Principal Investigator: Gang Zhao, M.D. Neurology Department,Xijing Hospital
Verification DateAugust 2013

Locations[ + expand ][ + ]

Xijing Hospital
Xi'an, Shaanxi, China, 710032
Contact: Fang Yang, M.D. Ph.D. | +86 029 84773214 | fyangx@fmmu.edu.cn
Principal Investigator: Gang Zhao, M.D.
Not yet recruiting