Reversal of the Anti-platelet Effects of Ticagrelor in Healthy Persons and Patients With Coronary Artery Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Reversal of the platelet inhibitory effects of antiplatelet therapy in patients
研究概览
简要总结
The purpose of this study is to determine the proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of ticagrelor and aspirin in healthy persons and patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) and receiving ticagrelor.
详细描述
Reversal of the Anti-platelet Effects of Ticagrelor: REVERSAL study
The fatality of stent thrombosis (ST) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) is approximately 50% and clopidogrel is an important anti-platelet drug for prevention of ST. CAD patients implanted with stent including bare metal stent (BMS) and drug eluting stent (DES) are recommended to receive dual anti-platelet treatment (DAPT), i.e. clopidogrel along with aspirin, for at least one year to reduce the incidence of ST by up-to-date guidelines. However, due to the variability of anti-platelet effect of clopidogrel, regular dose (75 mg daily) of clopidogrel administered cannot achieve enough inhibition of platelet aggregation in 20-30% of total patients, which is named as clopidogrel low responsiveness (CLR), and the morbidity of thrombosis (including) in CAD patients is still 10%.
Ticagrelor, a cyclopentyl-triazolo-pyrimidine, is a more potent adenosine diphosphate (ADP) receptor antagonist with faster onset and more significantly higher inhibition of platelet aggregation compared with clopidogrel and directly acts on P2Y12-ADP receptor in platelets without process of hepatic metabolism. In the PLATO study, ticagrelor plus reduced the remarkable incidence of cardiovascular events in patients with acute coronary syndrome (ACS) without significant higher incidence of major bleeding events compared with clopidogrel plus aspirin. Surprisingly, the incidence of death due to cardiovascular causes and the total fatality was decreased in patients with ticagrelor plus aspirin compared with those with clopidogrel plus aspirin. The results suggested the more benefit brought by ticagrelor, highlighting the wide use of it in the future.
Due to the potent anti-platelet effect of ticagrelor, more bleeding events may occur. Additionally, when facing the need for cardiac or non-cardiac operation, occurrence of life-threatening bleeding event or necessity of emergency operation, doctors may be confused of the treatment for the patients taking ticagrelor, of which the half-life period is 8-9 hours and it suggests the importance of studying the reversal of the anti-platelet effects of ticagrelor.
The primary objective of this study is to investigate the proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of aspirin and ticagrelor in healthy persons and patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) and receiving ticagrelor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers;
- •Subjects aged >18 years old;
排除标准
- •Allergy or intolerance to aspirin or ticagrelor;
- •Subjects at a high risk of bleeding (e.g. platelet count<100×10^9/L, history of peptic ulcer, hemoglobin<110g/L);
- •Subjects with anemia;
- •Subjects with bronchial asthma or chronic obstructive pulmonary disease;
- •Subjects with bradycardia (e.g. sick sinus syndrome, high-grade atrioventricular block, history of syncope with unproved uncorrelation with bradycardia);
- •Subjects with diabetes mellitus;
- •Subjects planning to be pregnancy;
- •Subjects with hepatic or renal dysfunction;
- •Subjects who have taken other anti-platelet drugs, non-steroidal anti-inflammatory drugs or proton pump inhibitors before scanning or need to take them during study period.
- •Inclusion Criteria:
- •Subjects with diagnosed coronary artery disease undergoing percutaneous coronary intervention (PCI);
- •Subjects who have received dual anti-platelet therapy (ticagrelor 90mg bid + aspirin 100mg daily) for 7 days;
- •Exclusion Criteria:
- •Subjects at a high risk of bleeding (e.g. platelet count<100×10^9/L, history of peptic ulcer, hemoglobin<110g/L);
- •Subjects with anemia;
- •Subjects planning to be pregnancy;
- •Subjects with hepatic or renal dysfunction;
- •Subjects who have taken other anti-platelet drugs, non-steroidal anti-inflammatory drugs or proton pump inhibitors before scanning or need to take them during study period.
研究组 & 干预措施
Single Anti-platelet Treatment
Ticagrelor
干预措施: Ticagrelor (Drug)
Dual Anti-platelet Treatment
Aspirin + Ticagrelor
干预措施: Aspirin + Ticagrelor (Drug)
Control
No Drug
干预措施: Control (Drug)
CAD undergoing PCI
Patients with coronary artery disease undergoing percutaneous coronary intervention and receiving dual anti-platelet therapy (ticagrelor 90mg bid + aspirin 100mg daily)
干预措施: Aspirin + Ticagrelor (Drug)
结局指标
主要结局
Reversal of the platelet inhibitory effects of antiplatelet therapy in patients
时间窗: 7 days after percutaneous coronary intervention
Reversal of the platelet inhibitory effects of antiplatelet therapy Proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) and receiving ticagrelor
Reversal of the platelet inhibitory effects of antiplatelet therapy in healthy volunteers
时间窗: 7 days after randomization
Proportion of untreated donor platelets required to fully reverse the platelet inhibitory effects of antiplatelet therapy
次要结局
- Inhibition of platelet aggregation in response to AA or ADP(7 days after randomization)
- Change of ADP-induced platelet aggregation in platelets saved in blood bank due to the saving time(5 days after fresh platelet collected and stored in blood bank)
研究者
Chunjian Li
Professor
The First Affiliated Hospital with Nanjing Medical University