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

Air Force Military Medical University of People's Liberation Army

Status and phase: Unknown; Phase 3; Phase 2

Conditions: TIA; Ischemic Stroke

Treatments: Drug: Apixaban; Drug: placebo; Drug: Aspirin; Drug: Clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT01924325

Xijing-ADANCE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10,000 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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10,000 participants in 3 patient groups

Dual-antiplatelet Therapy

Active Comparator group

Description:

Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily

Treatment:

Drug: Clopidogrel

Drug: Aspirin

Drug: placebo

Apixaban 2.5mg

Experimental group

Description:

Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21

Treatment:

Drug: placebo

Drug: Apixaban

Apixaban 5mg

Experimental group

Description:

Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21

Treatment:

Drug: placebo

Drug: Apixaban