Platelet Hyperreactivity to Aspirin and Stroke

NCT00766896 | Completed Phase 4 DMC

• 1 other identifier: 0292/07
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

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
• 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
• 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

Conditions

Stroke; Cerebral Infarction; Cardiovascular Diseases; Vascular Diseases; Atherosclerosis; Ischemia; Thrombosis; Acute Coronary Syndrome

Keywords

Stroke; Cerebral Infarction; Acute Coronary Syndrome; Cardiovascular Diseases; Vascular Diseases; Platelet Activation; Platelets; Platelet Function Tests; Aspirin; Atherosclerosis; Ischemia; Thrombosis

Outcome Measures

Primary Outcomes (1)

• 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

  Three, 12, 24, and 36 months

Secondary Outcomes (5)

• Primary outcomes for subgroups [(a) recent use of aspirin, (b) TOAST (c) SSS-TOAST]

  Three, 12, 24, 36 months

• Compare TOAST with SSS-TOAST

  During the initial hospitalization

• Severe bleeding

  Three, 12, 24, 36 months

• Prevalence, correlation and accuracy of various tests of platelet function

  Three, 12, 24, 36 months

• Correlation between platelet hyperreactivity and the clinical outcomes individually (TIA and stroke; acute coronary syndromes; death)

  Three, 12, 24, 36 months

Study Arms (2)

Aspirin Sensitive

ACTIVE COMPARATOR

* 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)

Platelet with hyperreactivity to aspirin

ACTIVE COMPARATOR

* 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)

Interventions

Aspirin (platelet sensitive versus platelet hyperreactivity) DRUG

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).

Also known as: Aspirin resistance

Aspirin Sensitive; Platelet with hyperreactivity to aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator
• Accumetrics, Inc.: collaborator
• Helena Laboratories Point of Care: collaborator
• Chrono-Log Corporation: collaborator

Study Sites (1)

University of Sao Paulo, School of Medicine

São Paulo, São Paulo, 05403000, Brazil

Location

MeSH Terms

Conditions

Stroke; Cerebral Infarction; Cardiovascular Diseases; Vascular Diseases; Atherosclerosis; Ischemia; Thrombosis; Acute Coronary Syndrome

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Infarction; Brain Ischemia; Infarction; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Embolism and Thrombosis; Myocardial Ischemia; Heart Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• 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 CHAIR

• 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

  PRINCIPAL INVESTIGATOR

• Moacyr RC Nobre, PHD

  University of Sao Paulo, Unidade de Epidemiologia Clínica

  STUDY DIRECTOR

• Luíz R Comerlatti, MD

  University of Sao Paulo, Hospital das Clínicas, Department of Neurology

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Herlon Saraiva Martins, M.D., Ph.D.

Study Record Dates

• First Submitted: October 2, 2008
• First Posted: October 6, 2008
• Study Start: July 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 24, 2013

Record last verified: 2013-06

Locations

BR (1)