Aortic Arch Related Cerebral Hazard Trial (ARCH)

NCT ID: NCT00235248

Last Updated: 2012-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2012-07-31

Brief Summary

The ARCH is a controlled trial with a sequential design and with a prospective, randomized, open-label, blinded-endpoint (PROBE) methodology. The objective is to compare the efficacy and tolerance (net benefit) of two antithrombotic strategies in patients with atherothrombosis of the aortic arch and a recent (less than 6 months) cerebral or peripheral embolic event.

Hypothesis:

The association of clopidogrel 75 mg/d plus aspirin 75 mg/d is 25% more effective than an oral anticoagulant (target International Normalized Ratio [INR] 2 to 3) in preventing brain infarction, brain hemorrhage, myocardial infarction, peripheral embolism, and vascular death.

Detailed Description

Patients with Transient Ischemic attack or brain infarction of unknown cause (no ipsilateral internal carotid artery origin stenosis greater than 70%, no ipsilateral severe intracranial stenosis of an artery supplying the infarcted area, no definite cardiac source of embolism) in the preceding 6 months and atherosclerotic plaques.

≥ 4 mm in the aortic arch, or patients with a peripheral event (e.g. renal infarct) in the preceding 6 months and plaque ≥ 4 mm in the thoracic aorta above the origin of the embolized artery.

Conditions

Brain Infarction; Transient Ischemic Attack; Embolism

Keywords

TIA/Brain infarct; and plaque>4mm in the aortic arch; Or peripheral embolism; and plaque>4 mm in the thoracic aorta

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Clopidogrel-aspirin

Clopidogrel-aspirin

Group Type: EXPERIMENTAL

Clopidogrel-aspirin

Intervention Type: DRUG

Clopidogrel-aspirin

Warfarin

Warfarin

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

Warfarin

Interventions

Warfarin

Warfarin

Intervention Type: DRUG

Clopidogrel-aspirin

Clopidogrel-aspirin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• One of the 3 following ischemic events in the preceding 6 months:

• Transient ischemic attack (TIA)
• Non-disabling brain infarcts:

• Inclusion within 6 months after onset
• Duration of symptoms and signs greater than 24 hours
• Neurological signs at the time of randomization with a Rankin Scale grade 3 or less
• With normal computed tomography (CT) scan or CT scan showing a brain infarct (even hemorrhagic infarct)
• Peripheral embolism
• Atherosclerotic plaque in the thoracic aorta is defined as wall thickness ≥ 4 mm where the protruding material is the largest, measured at transesophageal echocardiography with multiplane transducer or a plaque less than 4 mm but with mobile component.
• Informed consent signed
• Life expectancy > 3 years

Exclusion Criteria

• Other causes of embolism:

• Cardiac: endocarditis, atrial fibrillation, intra-cardiac thrombus, valvular prosthesis, rheumatic valvulopathy, left ventricular aneurysm, or ejection fraction less than 25%
• Atherosclerotic stenosis ipsilateral to the embolic territory: internal carotid artery stenosis greater than 70%, or severe (judgment of the investigator) intracranial stenosis, or scheduled carotid endarterectomy (in that case inclusion is possible 30 days after the procedure)
• Uncommon causes: dissection, vasculitis, procoagulant state, or sickle cell disease

• Intercurrent illness with life expectancy less than 36 months
• Pregnancy and non-menopausal women
• Unwillingness to participate
• Poor medication compliance expected
• Toxicomania
• Absolute indication for anticoagulant therapy (e.g. atrial fibrillation, intracardiac thrombus, prosthetic valve)
• Scheduled for carotid endarterectomy (randomization is possible 30 days after endarterectomy)
• CT scan with an intracranial lesion other than brain infarction (space occupying mass, intracranial hemorrhage)
• Transesophageal echocardiography (TEE) with plaque ≥ 4 mm in thickness distal to the supposed embolized artery (judgement of the investigator).
• Contraindication to clopidogrel, aspirin, and oral anticoagulants

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre Amarenco, Pr, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

National Stroke Research Institute-Austin Health

Heidelberg Heights, , Australia

Bichat Hospital Head of Neurology Department

Paris, , France

Countries

Australia; France

References

Amarenco P, Davis S, Jones EF, Cohen AA, Heiss WD, Kaste M, Laouenan C, Young D, Macleod M, Donnan GA; Aortic Arch Related Cerebral Hazard Trial Investigators. Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke. 2014 May;45(5):1248-57. doi: 10.1161/STROKEAHA.113.004251. Epub 2014 Apr 3.

Reference Type: DERIVED

PMID: 24699050 (View on PubMed)

Other Identifiers

P991205

Identifier Type: -

Identifier Source: org_study_id