Aortic Arch Related Cerebral Hazard Trial (ARCH)
Aortic Arch Related Cerebral Hazard Trial (ARCH)
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.
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.
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