Aortic Arch Related Cerebral Hazard Trial (ARCH)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prevention of New Vascular Events in Patients With Brain Infarction or Peripheral Embolism and Thoracic Aortic Plaques ≥ 4 mm in Thickness in the Aortic Arch or Descending Aortic Upstream to the Embolized Artery

Conditions
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Embolism, Brain Infarction, Transient Ischemic Attack

Intervention / Treatment
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* Drug: Warfarin
* Drug: Clopidogrel-aspirin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clopidogrel-aspirin<br>Clopidogrel-aspirin | Drug: Clopidogrel-aspirin<br>* Clopidogrel-aspirin<br>|
| Active Comparator: Warfarin<br>Warfarin | Drug: Warfarin<br>* Warfarin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent brain infarction | Recurrent brain infarction | during the trial | 
| brain infarction and transient ischemic attack (TIA) | brain infarction and transient ischemic attack (TIA) | during the studing | 
| new vascular events and revascularization procedure | new vascular events and revascularization procedure | during the trial | 
| vascular death | vascular death | during the trial | 
| death from all causes | death from all causes | during the trial | 
| combination of primary end-point and TIA | combination of primary end-point and TIA | during the trial | 
| revascularization procedures | revascularization procedures | during the trial | 
| urgent rehospitalization for ischemic | urgent rehospitalization for ischemic | during the trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIA/Brain infarct, and plaque>4mm in the aortic arch, Or peripheral embolism, and plaque>4 mm in the thoracic aorta