Aortic Arch Related Cerebral Hazard Trial (ARCH)

• Status: Completed
• Trial end date: 2012-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Bristol-Myers Squibb; National Health and Medical Research Council, Australia; Sanofi
• Treatments: Aspirin; Clopidogrel; Ticlopidine; Warfarin

Criteria

Inclusion Criteria:

Patients of both sexes aged ≥ 18 years with the following 4 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

• Other exclusion criteria:

• 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