Comparison of Serum Thromboxane B2 and Platelet Function Testing With the Multiplate® Device as Measures of Aspirin Resistance in Hong Kong Chinese Patients With Increased Cardiovascular Risk With Stable Coronary Heart Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 266
- 试验地点
- 1
- 主要终点
- serum thromboxane B2 (TXB2) concentrations
研究概览
简要总结
The hypotheses of the study are that the diagnostic accuracy of Multiplate® device for diagnosis of aspirin resistance is comparable to the serum TXB2 assay and that certain genetic polymorphisms and phenotypic factors significantly influence the antiplatelet effect of aspirin and contribute to aspirin resistance observed in this study.
详细描述
Fasting blood samples will be obtained from patients in the study centre after fasting overnight for at least 10 hours immediately before and 1 hour after the 80 mg aspirin dose. A 5-ml blood sample will be obtained in a serum separator tube and allowed to clot at room temperature followed by centrifugation at 4 degrees C. Separated serum will be stored in aliquots at -80°C until analysis of TXB2. A 3-ml blood sample will be obtained in a hirudin blood tube for the platelet aggregation test with the Multiplate® analyzer which will be performed within 3 hours after blood collection. A 10 ml blood sample will be obtained in an ethylene diamine tetra acetic acid (EDTA) tube to be used for DNA extraction. During the study, a total of 26 ml blood will be taken from each participant. Morning urine samples before and 1 hour after aspirin ingestion will also be collected and stored at -80 °C until measurement.
The platelet activity of the samples will be measured with the hirudin blood using the Multiplate analyzer from Roche (Roche Diagnostics International Ltd, CH-6343 Rotkreuz, Switzerland) according to the manufacturer's instructions for the arachidonic acid induced platelet aggregation (ASPI) test. It will be analyzed within 0.5-3 hours after blood collection.
The serum samples will be assayed for TXB2 with EIA kits from Cayman (Item no. 501020, Cayman Chemical, MI, USA) according to the manufacturer's instructions.
The urine will be assayed for 11-dehydro TXB2 using the enzyme-linked immunosorbent assay (EIA) kit from Cayman (Item no. 519510, Cayman Chemical, MI, USA) according to the manufacturer's instructions. The data will then be standardized with urinary creatinine measured with Cayman creatinine (urinary) colorimetric assay kit (item no 500701).
The 11-dehydro TXB2 data will be standardized with the urinary creatinine levels measured by Creatinine (urinary) Colorimetric Assay kit from Cayman (Item no. 500701, Cayman Chemical, MI, USA) according to the manufacturer's instructions.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Patients aged ≥ 18 years who have a history of stable CHD receiving long-term mono-antiplatelet therapy with aspirin (80 mg once daily) for reducing cardiovascular risk will be recruited from the outpatient clinic.
排除标准
- •Patients who are currently taking ticlopidine, clopidogrel, dipyridamole or other antiplatelet / antithrombotic agents will not be recruited.
- •Patients who are on regular therapy with anti-inflammatory drugs, or others drugs containing aspirin or non-steroid anti-inflammatory drugs (NSAIDS), or traditional Chinese medicine that have direct effects on the haemostatic system, such as angelica, danshen, garlic, ginger, ginkgo and motherwort will not be included unless they are willing to stop these treatments for at least 2 weeks
- •Patients will not be recruited if they had MI, stroke, coronary artery bypass surgery or other revascularization procedure, unstable angina or angioplasty within 3 months of screening.
结局指标
主要结局
serum thromboxane B2 (TXB2) concentrations
时间窗: Through study completion, an average of 1 year.
Serum TXB2 concentrations will be measured by using an enzyme immunoassay kit to assess the adequacy of platelet cyclooxygenase (COX)-1 inactivation by aspirin. Each subject will only attend on one day.
次要结局
- Genotyping of COX1 gene, which may be related to aspirin antiplatelet effect.(Through study completion, an average of 1 year.)
- Multiplate® analyzer aspirin assay (ASPI test) platelet aggregation test(Through study completion, an average of 1 year.)
- Genotyping of thromboxane A2 receptor (TBXA2R) gene, which may be related to aspirin antiplatelet effect.(Through study completion, an average of 1 year.)
研究者
Brian Tomlinson
Professor
Chinese University of Hong Kong