Aortic Arch Related Cerebral Hazard Trial (ARCH)

Transient Ischemic Attack Clinical Trial

— ARCH  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00235248
• Other study ID #: P991205
• Status: Completed
• Phase: Phase 3
• First received: October 6, 2005
• Last updated: July 6, 2012
• Start date: February 2002
• Est. completion date: July 2012

Study information

• Verified date: July 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: July 2012
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Infarction
• Embolism
• Infarction
• Ischemic Attack, Transient
• Transient Ischemic Attack

Intervention

Drug:
• Warfarin
Warfarin
• Clopidogrel-aspirin
Clopidogrel-aspirin

Locations

Country	Name	City	State
Australia	National Stroke Research Institute-Austin Health	Heidelberg Heights
France	Bichat Hospital Head of Neurology Department	Paris

Sponsors (4)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Bristol-Myers Squibb, National Health and Medical Research Council, Australia, Sanofi

Countries where clinical trial is conducted

Australia,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Recurrent brain infarction	Recurrent brain infarction	during the trial	Yes
Secondary	brain infarction and transient ischemic attack (TIA)	brain infarction and transient ischemic attack (TIA)	during the studing	Yes
Secondary	new vascular events and revascularization procedure	new vascular events and revascularization procedure	during the trial	Yes
Secondary	vascular death	vascular death	during the trial	No
Secondary	death from all causes	death from all causes	during the trial	No
Secondary	combination of primary end-point and TIA	combination of primary end-point and TIA	during the trial	Yes
Secondary	revascularization procedures	revascularization procedures	during the trial	Yes
Secondary	urgent rehospitalization for ischemic	urgent rehospitalization for ischemic	during the trial	Yes