Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2013 by Xijing Hospital
Sponsor:
Information provided by (Responsible Party):
Xijing Hospital
ClinicalTrials.gov Identifier:
NCT01924325
First received: August 13, 2013
Last updated: NA
Last verified: August 2013
History: No changes posted

August 13, 2013
August 13, 2013
January 2014
December 2015   (final data collection date for primary outcome measure)
percentage of patients with new stroke (ischemic or hemorrhage) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
  • 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 ]
Same as current
Not Provided
Not Provided
 
Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in Acute Non-disabling Cerebrovascular Events
Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in High-risk Patients With Acute Non-disabling Cerebrovascular Events (ADANCE): Rationale, Objectives, and Design

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Ischemic Stroke
  • TIA
  • Drug: 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 Name: Acetylsalicylic acid
  • Drug: placebo
  • 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
    Interventions:
    • Drug: Clopidogrel
    • Drug: Aspirin
    • Drug: placebo
  • 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
    Interventions:
    • Drug: Apixaban
    • Drug: placebo
  • Experimental: Apixaban 5mg
    Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21
    Interventions:
    • Drug: Apixaban
    • Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
10000
July 2016
December 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years to 80 Years
No
Contact: Xuedong Liu, M.D. +86 029 84775055 liuxued@fmmu.edu.cn
China
 
NCT01924325
Xijing-ADANCE
Yes
Xijing Hospital
Xijing Hospital
Not Provided
Principal Investigator: Gang Zhao, M.D. Neurology Department,Xijing Hospital
Xijing Hospital
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP