Clinical trial NCT00235248: Aortic Arch Related Cerebral Hazard 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Infarction
Transient Ischemic Attack
Embolism
Keywords: TIA/Brain infarct
and plaque>4mm in the aortic arch
Or peripheral embolism
and plaque>4 mm in the thoracic aorta
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Sanofi
name: Bristol-Myers Squibb
First posted: 2005-10-10
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: New vascular events assessed every 4 months including stroke, myocardial infarction (MI), peripheral events, and vascular death
timeFrame: every 4 months
Secondary outcomes:
measure: Recurrent brain infarction
timeFrame: during the trial
measure: brain infarction and transient ischemic attack (TIA)
timeFrame: during the studing
measure: new vascular events and revascularization procedure
timeFrame: during the trial
measure: vascular death
timeFrame: during the trial
measure: death from all causes
timeFrame: during the trial
measure: combination of primary end-point and TIA
timeFrame: during the trial
measure: revascularization procedures
timeFrame: during the trial
measure: urgent rehospitalization for ischemic
timeFrame: during the trial
Other outcomes:
Locations:
city: Heidelberg Heights
country: Australia
facility: National Stroke Research Institute-Austin Health
city: Paris
country: France
facility: Bichat Hospital Head of Neurology Department
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pierre Amarenco, Pr, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amarenco P, Davis S, Jones EF, Cohen AA, Heiss WD, Kaste M, Laouenan C, Young D, Macleod M, Donnan GA; Aortic Arch Related Cerebral Hazard Trial Investigators. Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke. 2014 May;45(5):1248-57. doi: 10.1161/STROKEAHA.113.004251. Epub 2014 Apr 3.