Aortic Arch Related Cerebral Hazard Trial (ARCH)

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00235248

Collaborator

National Health and Medical Research Council, Australia (Other), Sanofi (Industry), Bristol-Myers Squibb (Industry)

350

Enrollment

Locations

Arms

124.9

Duration (Months)

175

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Infarction Transient Ischemic Attack Embolism	Drug: Warfarin Drug: Clopidogrel-aspirin	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

350 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clopidogrel-aspirin Clopidogrel-aspirin	Drug: Clopidogrel-aspirin Clopidogrel-aspirin
Active Comparator: Warfarin Warfarin	Drug: Warfarin Warfarin

Arm

Intervention/Treatment

Experimental: Clopidogrel-aspirin

Clopidogrel-aspirin

Drug: Clopidogrel-aspirin

Clopidogrel-aspirin

Active Comparator: Warfarin

Warfarin

Drug: Warfarin

Warfarin

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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