Aortic Arch Related Cerebral Hazard Trial (ARCH)

This study has been completed.
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Sanofi
Bristol-Myers Squibb
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00235248
First received: October 6, 2005
Last updated: July 6, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Brain Infarction
Transient Ischemic Attack
Embolism
Drug: Warfarin
Drug: Clopidogrel-aspirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • New vascular events assessed every 4 months including stroke, myocardial infarction (MI), peripheral events, and vascular death [ Time Frame: every 4 months ] [ Designated as safety issue: Yes ]
    New vascular events assessed every 4 months including stroke, myocardial infarction (MI), peripheral events, and vascular death


Secondary Outcome Measures:
  • Recurrent brain infarction [ Time Frame: during the trial ] [ Designated as safety issue: Yes ]
    Recurrent brain infarction

  • brain infarction and transient ischemic attack (TIA) [ Time Frame: during the studing ] [ Designated as safety issue: Yes ]
    brain infarction and transient ischemic attack (TIA)

  • new vascular events and revascularization procedure [ Time Frame: during the trial ] [ Designated as safety issue: Yes ]
    new vascular events and revascularization procedure

  • vascular death [ Time Frame: during the trial ] [ Designated as safety issue: No ]
    vascular death

  • death from all causes [ Time Frame: during the trial ] [ Designated as safety issue: No ]
    death from all causes

  • combination of primary end-point and TIA [ Time Frame: during the trial ] [ Designated as safety issue: Yes ]
    combination of primary end-point and TIA

  • revascularization procedures [ Time Frame: during the trial ] [ Designated as safety issue: Yes ]
    revascularization procedures

  • urgent rehospitalization for ischemic [ Time Frame: during the trial ] [ Designated as safety issue: Yes ]
    urgent rehospitalization for ischemic


Enrollment: 350
Study Start Date: February 2002
Study Completion Date: July 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clopidogrel-aspirin
Clopidogrel-aspirin
Drug: Clopidogrel-aspirin
Clopidogrel-aspirin
Other Name: Clopidogrel-aspirin
Active Comparator: Warfarin
Warfarin
Drug: Warfarin
Warfarin
Other Name: Warfarin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00235248

Locations
Australia
National Stroke Research Institute-Austin Health
Heidelberg Heights, Australia, Vic 3081
France
Bichat Hospital Head of Neurology Department
Paris, France, 75018
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
National Health and Medical Research Council, Australia
Sanofi
Bristol-Myers Squibb
Investigators
Principal Investigator: Pierre Amarenco, Pr, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided by Assistance Publique - Hôpitaux de Paris

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00235248     History of Changes
Other Study ID Numbers: P991205
Study First Received: October 6, 2005
Last Updated: July 6, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
TIA/Brain infarct
and plaque>4mm in the aortic arch
Or peripheral embolism
and plaque>4 mm in the thoracic aorta

Additional relevant MeSH terms:
Ischemic Attack, Transient
Embolism
Infarction
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Embolism and Thrombosis
Ischemia
Pathologic Processes
Necrosis
Stroke
Aspirin
Ticlopidine
Clopidogrel
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014