Platelet Hyperreactivity to Aspirin and Stroke (PLARAS)

This study has been completed.
Sponsor:
Collaborators:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Accumetrics, Inc.
Helena Laboratories Point of Care
Chrono-Log Corporation
Information provided by (Responsible Party):
Herlon Saraiva Martins, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT00766896
First received: October 2, 2008
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

STUDY QUESTIONS

  • What is the real prevalence of platelet "resistance" to aspirin during the acute phase of stroke and after 3 months, and 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?

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 (acute phase)
    • Comparison of different assessment methods and identification of the most accurate of these
    • Identification of variables that correlate with platelet hyperreactivity
  2. Follow-up Phase

    • Correlation between platelet hyperreactivity and important clinical outcomes at 12, 24, and 36 months
    • Correlation between platelet hyperreactivity and death or dependency at hospital discharge, at 3, 12, 24, and 36 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
  • 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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Platelet Hyperreactivity to Aspirin and Stroke: A Prospective Study With Clinical Outcomes

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:
  • Correlation between platelet hyperreactivity and the sum of clinical outcomes (sum of death, TIA, stroke and acute coronary syndromes) in 3, 12, 24, and 36 months [ Time Frame: Three, 12, 24, and 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Primary outcomes for subgroups [(a) recent use of aspirin, (b) TOAST (c) SSS-TOAST] [ Time Frame: Three, 12, 24, 36 months ] [ Designated as safety issue: No ]
  • Compare TOAST with SSS-TOAST [ Time Frame: During the initial hospitalization ] [ Designated as safety issue: No ]
  • Severe bleeding [ Time Frame: Three, 12, 24, 36 months ] [ Designated as safety issue: Yes ]
  • Prevalence, correlation and accuracy of various tests of platelet function [ Time Frame: Three, 12, 24, 36 months ] [ Designated as safety issue: No ]
  • Correlation between platelet hyperreactivity and the clinical outcomes individually (TIA and stroke; acute coronary syndromes; death) [ Time Frame: Three, 12, 24, 36 months ] [ Designated as safety issue: No ]

Enrollment: 203
Study Start Date: July 2009
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aspirin Sensitive
  • For PFA-100 using a cartridge with C-EPI (collagen-epinephrine): occlusion time >= 150 seconds
  • Chrono-Log Model 700 Whole-Blood: < 1Ω with 0.75 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
  • Chrono-Log Model 700 Whole-Blood: with collagen at 1 mg/L < 10Ω
  • 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).
Other Name: Aspirin resistance
Active Comparator: Platelet with hyperreactivity to aspirin
  • For PFA-100 using a cartridge with C-EPI (collagen-epinephrine): occlusion time < 150 s
  • Chrono-Log Whole-Blood: above or = 1Ω with 0.75 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
  • Chrono-Log Whole-Blood: with collagen 1 mg/L above or = 10Ω
  • 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).
Other Name: Aspirin resistance

  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
  • Creatinine clearance below 30 mL/min
  • Platelet count <100,000/mm3
  • Hematocrit <30%
  • Lipaemic blood
  • 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
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: NCT00766896

Locations
Brazil
University of Sao Paulo, School of Medicine
Sao Paulo, SP, Brazil, 05403000
Sponsors and Collaborators
University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Accumetrics, Inc.
Helena Laboratories Point of Care
Chrono-Log 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: Élbio A D'Amico, PHD University of Sao Paulo, Hospital das Clínicas, Department of Hematology
Principal Investigator: 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
Principal Investigator: Luíz R Comerlatti, MD University of Sao Paulo, Hospital das Clínicas, Department of Neurology
Study Director: Cláudia C Leite, PHD University of Sao Paulo, Hospital das Clínicas, Department of Radiology
Study Director: José L Andrade, MD University of Sao Paulo, Hospital das Clínicas, Department of Radiology
  More Information

No publications provided

Responsible Party: Herlon Saraiva Martins, Herlon Saraiva Martins, M.D., Ph.D., University of Sao Paulo
ClinicalTrials.gov Identifier: NCT00766896     History of Changes
Other Study ID Numbers: 0292/07
Study First Received: October 2, 2008
Last Updated: June 20, 2013
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

Additional relevant MeSH terms:
Acute Coronary Syndrome
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Cerebral Infarction
Infarction
Ischemia
Stroke
Syndrome
Thrombosis
Vascular Diseases
Angina Pectoris
Arterial Occlusive Diseases
Brain Diseases
Brain Infarction
Brain Ischemia
Central Nervous System Diseases
Cerebrovascular Disorders
Chest Pain
Disease
Embolism and Thrombosis
Heart Diseases
Myocardial Ischemia
Necrosis
Nervous System Diseases
Pain
Pathologic Processes
Signs and Symptoms
Aspirin
Analgesics

ClinicalTrials.gov processed this record on October 20, 2014