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临床试验/NCT06228820
NCT06228820已完成2 期

Aspirin Resistance in Trinidad: The ART Pilot Study.

The University of The West Indies1 个研究点 分布在 1 个国家目标入组 48 人开始时间: 2024年1月15日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
入组人数
48
试验地点
1
主要终点
Aspirin Resistance Unit

研究概览

简要总结

Aspirin's beneficial effect is mediated via the inhibition of arachidonic acid (AA) activation of platelets. It is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Besides inhibiting the formation of thromboxane A2 from arachidonic acid, Aspirin has a host of platelet-independent effects that complement its platelet-inhibitory effects.

The phenomenon of "Aspirin resistance" is based on the observation of clinical events in some patients taking Aspirin and/or a diminished platelet aggregation inhibitory response to Aspirin therapy. It has been suggested that many individuals taking Aspirin have become resistant to this drug. Unfortunately, laboratory assays used to monitor the efficacy of Aspirin are far from accurate, and the results are not reproducible. Multiple studies demonstrate non-compliance using repeat testing for platelet inhibition in patients with an initial inadequate response to Aspirin. When the test is repeated under the condition that the ingestion of the test Aspirin is assured, the patients' platelets are inhibited. Patients with an inadequate Aspirin response have an increased likelihood of subsequent vascular events.

详细描述

Aspirin is a wonder drug used for over 100 years for its analgesic and antipyretic effects. It is an inexpensive, readily available medication that reduces the risk of subsequent vascular disease by about 25% in patients with known occlusive vascular disease. For the past three decades, it has increasingly been used to prevent primary and secondary cardiovascular events.

Aspirin's beneficial effect is mediated via the inhibition of arachidonic acid (AA) activation of platelets. It is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Besides inhibiting the formation of thromboxane A2 from arachidonic acid, Aspirin has a host of platelet-independent effects that complement its platelet-inhibitory effects.

The phenomenon of "Aspirin resistance" is based on the observation of clinical events in some patients taking Aspirin and/or a diminished platelet aggregation inhibitory response to Aspirin therapy. It has been suggested that many individuals taking Aspirin have become resistant to this drug. Unfortunately, laboratory assays used to monitor the efficacy of Aspirin are far from accurate, and the results are not reproducible. Multiple studies demonstrate non-compliance using repeat testing for platelet inhibition in patients with an initial inadequate response to Aspirin. When the test is repeated under the condition that the ingestion of the test Aspirin is assured, the patients' platelets are inhibited. Patients with an inadequate Aspirin response have an increased likelihood of subsequent vascular events.

The POINT pilot study introduced the preliminary observation that the estimated prevalence of HPR is considerably higher within the heterogeneous population in Trinidad at 50% compared with predominantly Caucasian studies. Furthermore, the HPR is significantly higher in South Asians (Indo-Trinidadians) (>60% of patients), which has severe clinical repercussions considering the cardiovascular disease pandemic. Clopidogrel may not be a satisfactory or optimal antiplatelet agent in this subgroup. Therefore, another more potent antiplatelet, such as ticagrelor, should be used instead.

Patients generally displayed a limited level of cardiovascular medication adherence, which is likely to translate into a higher rate of cardiovascular events with their potentially devastating sequelae.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 74 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • between 18 and 74 years of age,
  • healthy with no overt medical conditions,
  • not on any physician-prescribed medications or complementary/alternative therapies,

排除标准

  • presence of active internal bleeding or history of bleeding diathesis or clinical findings associated with an increased risk of bleeding,
  • history of ischemic or hemorrhagic stroke, transient ischemic attack, intracranial neoplasm, arteriovenous malformation, or aneurysm,
  • clinical and/or hemodynamic instability,
  • within 1 month of placement of a bare metal stent,
  • within 30 days of coronary artery bypass graft surgery or PCI without a stent placed,
  • planned coronary revascularization,
  • treatment with fibrin-specific fibrinolytic therapy <24 h or non-fibrin-specific fibrinolytic therapy <48 h,
  • use of an oral anticoagulation agent or international normalized ratio >1.5,
  • body weight <60 kg,
  • age >75 years,
  • hemoglobin <10 g/dL,
  • platelet count <100×106/μL,
  • creatinine >2 mg/dL,
  • hepatic enzymes >2.5 times the upper limit of normal,
  • pregnancy and/or lactation,
  • the patient is on any other antithrombotic therapies such as ticagrelor, dabigatran, rivaroxaban and apixaban

研究组 & 干预措施

Aspirin Arm

Experimental

Healthy patients will then undergo at least a 2-week course of 81mg of Bayer Aspirin per oral daily, followed by platelet function testing. The patients will then undergo a washout period of 2 weeks, followed by another 2-week course of 81mg Vazalore Aspirin per oral daily, followed by a second round of platelet function testing.

干预措施: Aspirin 81Mg Ec Tab (Drug)

结局指标

主要结局

Aspirin Resistance Unit

时间窗: 2-weeks

VerifyNow Aspirin assay is a qualitative test to aid in detecting platelet dysfunction due to Aspirin ingestion in whole blood for the point-of-care or laboratory setting. The assay incorporates the agonist arachidonic acid to activate platelets, and it measures platelet function based on the ability of activated platelets to bind to fibrinogen. Fibrinogen-coated microparticles aggregate in whole blood in proportion to the number of activated platelet GP IIb/IIIa receptors. If Aspirin has produced the expected antiplatelet effect, such aggregation will be reduced. The VerifyNow Aspirin assay reports the extent of platelet aggregation as Aspirin reaction units (ARUs). Given an ARU range of 350-700, ARU values less than 550 are consistent with Aspirin-induced inhibition of platelet function. In contrast, values greater than or equal to 550 ARUs are not compatible with Aspirin-induced inhibition.

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Naveen Seecheran

Principal Investigator

The University of The West Indies

研究点 (1)

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