Aortic Arch Related Cerebral Hazard Trial (ARCH)

NCT00235248 | Completed Phase 3 DMC

• 1 other identifier: P991205
• Study Type: interventional
• Target: 350
• Locations: 2 countries
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (1)

• New vascular events assessed every 4 months including stroke, myocardial infarction (MI), peripheral events, and vascular death

  New vascular events assessed every 4 months including stroke, myocardial infarction (MI), peripheral events, and vascular death

  every 4 months

Secondary Outcomes (8)

• Recurrent brain infarction

  during the trial

• brain infarction and transient ischemic attack (TIA)

  during the studing

• new vascular events and revascularization procedure

  during the trial

• vascular death

  during the trial

• death from all causes

  during the trial

Study Arms (2)

Clopidogrel-aspirin

EXPERIMENTAL

Clopidogrel-aspirin

Drug: Clopidogrel-aspirin

Warfarin

ACTIVE COMPARATOR

Warfarin

Drug: Warfarin

Interventions

Warfarin DRUG

Warfarin

Warfarin

Clopidogrel-aspirin DRUG

Clopidogrel-aspirin

Clopidogrel-aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One of the 3 following ischemic events in the preceding 6 months:
• Transient ischemic attack (TIA)
• Non-disabling brain infarcts:
• 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

You may not qualify if:

• Other causes of embolism:
• Cardiac: endocarditis, atrial fibrillation, intra-cardiac thrombus, valvular prosthesis, rheumatic valvulopathy, left ventricular aneurysm, or ejection fraction less than 25%
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• National Health and Medical Research Council, Australia: collaborator
• Sanofi: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (2)

National Stroke Research Institute-Austin Health

Heidelberg Heights, Vic 3081, Australia

Location

Bichat Hospital Head of Neurology Department

Paris, 75018, France

Location

Related Publications (1)

• 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.

  PMID: 24699050 DERIVED

MeSH Terms

Conditions

Brain Infarction; Ischemic Attack, Transient; Embolism

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pierre Amarenco, Pr, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2005
• First Posted: October 10, 2005
• Study Start: February 1, 2002
• Primary Completion: December 1, 2010
• Study Completion: July 1, 2012
• Last Updated: July 10, 2012

Record last verified: 2012-07

Locations

FR (1); AU (1)