Platelet Hyperreactivity to Aspirin and Stroke: A Prospective Study With Clinical Outcomes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 203
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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
详细描述
THE CONTEXT
Aspirin is the anti-thrombotic therapy of choice for patients in the acute or chronic phase of vascular, cardiac, and neurological diseases, unless there is a specific indication for sodium warfarin (for instance, cardiac thrombus, chronic atrial fibrillation, cardio-embolic ischemic stroke). Recent studies, including some meta-analyses, suggest that 5-60% of patients with cardiovascular disease who use aspirin show some platelet resistance to the drug. However, the available studies include several methodological errors that make interpretation and practical application difficult. Thus, the incidence and outcome of platelet resistance remain poorly understood, especially in patients with ischemic stroke. Moreover, few studies have included patients in ambulatory follow-up
THERAPY WITH ASPIRIN
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)
ANALYSIS OF OUTCOME DURING THE HOSPITAL PHASE
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consecutive patients with the diagnosis of ischemic stroke in the acute phase who will be treated with aspirin for an indefinite period
排除标准
- •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
研究组 & 干预措施
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
干预措施: Aspirin (platelet sensitive versus platelet hyperreactivity) (Drug)
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
干预措施: Aspirin (platelet sensitive versus platelet hyperreactivity) (Drug)
结局指标
主要结局
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
时间窗: Three, 12, 24, and 36 months
次要结局
- Compare TOAST with SSS-TOAST(During the initial hospitalization)
- Primary outcomes for subgroups [(a) recent use of aspirin, (b) TOAST (c) SSS-TOAST](Three, 12, 24, 36 months)
- 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)
研究者
Herlon Saraiva Martins
Herlon Saraiva Martins, M.D., Ph.D.
University of Sao Paulo