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Platelet Hyperreactivity to Aspirin and Stroke (PLARAS)
This study is currently recruiting participants.
Verified by University of Sao Paulo, September 2008
Sponsors and Collaborators: University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Accumetrics, Inc.
Helena Laboratories Point of Care
Corgenix Medical Corporation
Chrono-Log Corporation
Siemens Healthcare Diagnostics Inc
Haemonetics Corporation
Diamed Corporation
Information provided by: University of Sao Paulo
ClinicalTrials.gov Identifier: NCT00766896
  Purpose

STUDY QUESTIONS

  • What is the real prevalence of platelet "resistance" to aspirin during the acute phase of stroke and after 1 year, as measured using different platelet function tests?
  • Do all methods measure similar levels of resistance, or are some methods more sensitive than others?
  • Does this resistance result in a worse clinical prognosis? Is this result independent of other variables?

PRIMARY OBJECTIVES

  1. Hospital Phase (Acute Stroke)

    • Determination, using various methods, of the prevalence of platelet hyperreactivity in patients treated with aspirin to treat ischemic stroke
    • Comparison of different assessment methods and identification of the most accurate of these
    • Assessment of whether platelet hyperreactivity is associated with poor prognosis (higher incidence of adverse clinical outcomes during hospitalization)
    • Identification of variables that correlate with platelet hyperreactivity

  2. Follow-up Phase

    • Correlation between platelet hyperreactivity and important clinical outcomes at 12 months
    • Correlation between platelet hyperreactivity and death or dependency at hospital discharge, at 3 months, and at 12 months (Modified Rankin Scale)
    • Correlation between platelet hyperreactivity and recurrent stroke of any type
    • Correlation between different methods for evaluating platelet functions and identification of the most accurate method
    • Analysis of hyperreactivity over time

THE STUDY

  • The study will include 200 consecutive patients seen in the emergency department of a large, urban hospital (1500 inpatient beds) and diagnosed with stroke in the acute phase; these patients will be treated with aspirin for an undetermined period
  • The investigators will not include patients who require full anticoagulation treatment, regardless of the cause
  • Importantly, the analysis of primary and secondary outcomes will be carried out after blinding the examiner to the results of the platelet aggregation tests

PLATELET TESTS

  • Whole Blood Aggregometer, ChronoLog
  • VerifyNow, Accumetrics
  • PFA-100, Siemens
  • Plateletworks, Helena
  • Impact-R, Diamed
  • Urinary 11-dehydro-thromboxane B2 (Aspirinworks, Corgenix)
  • Serum thromboxane B2

Condition Intervention Phase
Stroke
Cerebral Infarction
Cardiovascular Diseases
Vascular Diseases
Atherosclerosis
Ischemia
Thrombosis
Acute Coronary Syndrome
 Drug: Aspirin (platelet sensitive versus platelet hyperreactivity)
 Phase IV

MedlinePlus related topics: Vascular Diseases
Drug Information available for: Acetylsalicylic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Diagnostic, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title: Platelet Hyperreactivity to Aspirin and Stroke: A Prospective Study With Clinical Outcomes

Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:
  • Phase hospital: prevalence of hyperreactivity; correlation between the hyperreactivity and (a) early neurological deterioration (b) sum of death and nonfatal events (c) death or dependence at hospital discharge [ Time Frame: During the initial hospitalization ] [ Designated as safety issue: No ]
  • Phase cohort: correlation between hyperreactivity and (a) the sum of clinical outcomes in three and twelve months, (b) compare the various methods and accuracy [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Initial phase: (1) primary outcomes for subgroups [(a) recent use of aspirin, (b) TOAST (c) SSS-TOAST], (2) compare TOAST with SSS-TOAST, (3) correlation between hyperreactivity and the sum of death and nonfatal neurological events, (4) severe bleeding [ Time Frame: During the initial hospitalization ] [ Designated as safety issue: Yes ]
  • Phase cohort: (1) primary outcomes for subgroups [(a) TOAST (b) SSS-TOAST], (2) death, (3) severe bleeding, (4) sum of ischemic stroke and TIA, (5) sum of cardiac outcomes, (6) severe bleeding, (7) behavior of hyperreactivity over time [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: October 2008
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Aspirin Sensitive: Active Comparator
  • For PFA-100 using a cartridge with C-EPI (collagen-epinephrine): occlusion time > 203 seconds
  • Chrono-Log Model 700 Whole-Blood: < 6Ω with 0.5 mM of arachidonic acid
  • Chrono-Log Model 700 Whole-Blood: with collagen at 1 mg/L and 5 mg/L, according to the formula 1 - (Rate of aggregation with 1 mg / Rate of aggregation with 5 mg) > 0.50
  • Aspirinworks (11-dehydro-thromboxane B2): the inferior quintile will be considered sensitive (expressed in pg of 11-dehydro thromboxane B2 / mg of creatinine)
  • Plateletworks: aggregation <60% with arachidonic acid will be considered sensitive
  • VerifyNow Aspirin Assay (Accumetrics): < 550 aspirin reaction units (ARUs)
  • Impact-R (Diamed) < 3.2% platelet aggregates on the surface of the plate after incubation with arachidonic acid
 Drug: Aspirin (platelet sensitive versus platelet hyperreactivity)
The dose of aspirin to be prescribed in this study will be 300 mg orally or by nasogastric tube once a day (assisted therapy), with first dose tomography soon after admission if the patient has no indication of thrombolytic therapy. After the acute phase, patients will receive aspirin at a dose of 200 mg/day. Aspirin will be administered in a "simple" preparation (no buffer, no extended release).
Platelet with hyperreactivity to aspirin: Active Comparator
  • For PFA-100 using a cartridge with C-EPI (collagen-epinephrine): occlusion time < 203 s
  • Chrono-Log Whole-Blood: above 6Ω with 0.5 mM of AA
  • Chrono-Log Whole-Blood: with collagen at 1 mg/L and 5 mg/L, according to the formula 1 - (Rate of aggregation with 1 mg / Rate of aggregation with 5 mg) below 0.50
  • Aspirinworks (11-dehydro-thromboxane B2): the top quintile will be considered hyper-reactive (expressed in pg of 11-dehydro thromboxane B2 / mg of creatinine)
  • Plateletworks: aggregation of more than 60% with arachidonic acid will be considered resistant
  • VerifyNow Aspirin Assay (Accumetrics): ≥ 550 aspirin reaction units (ARUs)
  • Impact-R (Diamed) > 3.2% platelet aggregates on the surface of the plate after incubation with arachidonic acid
 Drug: Aspirin (platelet sensitive versus platelet hyperreactivity)
The dose of aspirin to be prescribed in this study will be 300 mg orally or by nasogastric tube once a day (assisted therapy), with first dose tomography soon after admission if the patient has no indication of thrombolytic therapy. After the acute phase, patients will receive aspirin at a dose of 200 mg/day. Aspirin will be administered in a "simple" preparation (no buffer, no extended release).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Consecutive patients with the diagnosis of ischemic stroke in the acute phase who will be treated with aspirin for an indefinite period

Exclusion Criteria:

  • The need for full anticoagulation therapy for pulmonary embolism, deep vein thrombosis, chronic atrial fibrillation, thrombus in the left atrium or left ventricle, or for any other reason deemed relevant by the patient's physician
  • Thrombolytic treatment for stroke
  • History of allergy to aspirin (hives, swelling of glottis or anaphylaxis)
  • Risk of excessive bleeding due to active peptic ulcers, liver failure, history of bleeding or bleeding diathesis
  • Scheduled major or vascular surgery
  • Metastatic cancer or survival estimated at less than a year
  • Platelet count <100,000/mm3
  • Hematocrit <30%
  • Lipaemic blood
  • Contraindication to nuclear magnetic resonance (implanted metallic devices)
  • Difficult follow-up: patients with serious social problems, alcoholics, and residents of other states in the country
  • Refusal to participate in the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00766896

Contacts
Contact: Herlon S Martins, MD 551130696922 herlonsm@usp.br
Contact: Irineu T Velasco, PHD 551130696336 velasco@usp.br

Locations
Brazil, SP
Hospital das Clinicas, University of Sao Paulo, School of Medicine Recruiting
Sao Paulo, SP, Brazil, 05403000
Contact: Herlon S Martins, MD     551130696922     herlonsm@usp.br    
Contact: Irineu T Velasco, PHD     551130696336     velasco@usp.br    
Principal Investigator: Herlon S Martins, MD            
Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Accumetrics, Inc.
Helena Laboratories Point of Care
Corgenix Medical Corporation
Chrono-Log Corporation
Siemens Healthcare Diagnostics Inc
Haemonetics Corporation
Diamed Corporation
Investigators
Study Chair: Herlon S Martins, MD University of Sao Paulo, Hospital das Clinicas, Department of Emergency Medicine
Study Chair: Irineu T Velasco, PHD University of Sao Paulo, Hospital das Clínicas, Department of Emergency Medicine
Study Director: Adriana B Conforto, PHD University of Sao Paulo, Hospital das Clinicas, Department of Neurology
Study Director: Augusto Scalabrini-Neto, PHD University of Sao Paulo, Hospital das Clínicas, Department of Emergency Medicine
Study Director: Élbio A D'Amico, PHD University of Sao Paulo, Hospital das Clínicas, Department of Hematology
Study Director: Tânia RF Rocha, PHD University of Sao Paulo, Hospital das Clínicas, Department of Hematology
Study Director: Moacyr RC Nobre, PHD University of Sao Paulo, Unidade de Epidemiologia Clínica
Study Director: Eli F Evaristo, PHD University of Sao Paulo, Hospital das Clínicas, Department of Neurology
Study Director: Fábio Yamamoto, PHD University of Sao Paulo, Hospital das Clínicas, Department of Neurology
Study Director: Luíz R Comerlatti, MD University of Sao Paulo, Hospital das Clínicas, Department of Neurology
Study Director: Felipe I Reis, MD University of Sao Paulo, Hospital das Clínicas, Department of Emergency Medicine
Study Director: Cláudia C Leite, PHD University of Sao Paulo, Hospital das Clínicas, Department of Radiology
Study Director: Alfonso Barbato, PHD University of Sao Paulo, Hospital das Clínicas, Department of Radiology
Study Director: Milberto Scaff, PHD University of Sao Paulo
  More Information

Responsible Party: University of Sao Paulo ( Herlon Saraiva Martins )
Study ID Numbers: 0292/07
Study First Received: October 2, 2008
Last Updated: October 7, 2008
ClinicalTrials.gov Identifier: NCT00766896  
Health Authority: Brazil: National Committee of Ethics in Research;   Brazil: Ethics Committee

Keywords provided by University of Sao Paulo:
Stroke
Cerebral Infarction
Acute Coronary Syndrome
Cardiovascular Diseases
Vascular Diseases
Platelet Activation
 Platelets
Platelet Function Tests
Aspirin
Atherosclerosis
Ischemia
Thrombosis

Study placed in the following topic categories:
Atherosclerosis
Arterial Occlusive Diseases
Heart Diseases
Cerebral Infarction
Myocardial Ischemia
Stroke
Vascular Diseases
Central Nervous System Diseases
Ischemia
Arteriosclerosis
Brain Diseases
 Cerebrovascular Disorders
Thrombosis
Embolism and Thrombosis
Necrosis
Aspirin
Embolism
Acute Coronary Syndrome
Brain Ischemia
Brain Infarction
Infarction

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Disease
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Nervous System Diseases
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents
 Pathologic Processes
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Syndrome
Platelet Aggregation Inhibitors
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009



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