ETAMI-Study: Early Thienopyridine Treatment to Improve Primary Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 3
- 主要终点
- platelet reactivity index (PRI) measured by VASP phosphorylation
研究概览
简要总结
Acute myocardial infarction is generally caused by a thrombotic occlusion of coronary arteries. Primary aim of early therapy is a fast and complete reperfusion of the infarcted myocardium.
详细描述
This could be achieved by either thrombolytic therapy or primary Percutaneous coronary intervention (PCI).
Comparison of the different therapies in randomized trials shows an advantage of primary PCI regarding rates of recanalisation of the infarct vessel, preservation of left ventricular (LV) function, and reduction in the rate of reinfarctions. In addition, the in-hospital mortality is lower in patients undergoing primary PCI. Nevertheless, primary PCI does not always result in a successful reperfusion despite of successful restoration of blood flow in the epicardial infarct related artery.
Effective platelet inhibition is a cornerstone of therapy in patients with STEMI. In the ISIS-2 study acetylsalicylic acid (ASA) has been shown to improve short- and long-term clinical outcome in the same extent as fibrinolysis with streptokinase. Dual platelet inhibition with ASA and a thienopyridine has been repeatedly demonstrated to be more effective than ASA alone. Clopidogrel on top of ASA improved outcome in patients with acute coronary syndromes with and without PCI in the CURE study. Furthermore, a loading dose of 300 mg clopidogrel was advantageous in elective PCI in the CREDO trial and the addition of clopidogrel to ASA improved the patency rate of the infarct related artery in patients with STEMI undergoing fibrinolysis. In the BRAVE 3 study, the addition of abciximab to a background therapy of a high loading dose of 600 mg clopidogrel plus ASA did not result in an additional clinical benefit in terms of prevention of ischemic complications in primary elective PCI, suggesting a near optimal platelet inhibition with this treatment in primary PCI. The advantage of a 600 mg loading dose seems mainly related to the more rapid onset of the full antiplatelet effect within 2-4 hours as compared to 6-8 hours after 300 mg.
However, in patients with STEMI scheduled for primary PCI an earlier effective inhibition of ADP-induced platelet aggregation, preferably within 60-90 min after administration of the drug, is needed.
The new thienopyridine prasugrel has been shown to achieve a more complete and even more rapid platelet inhibition compared to clopidogrel. This might be especially important in patients with STEMI scheduled for primary PCI. In these patients activation of platelets is more pronounced compared to patients undergoing PCI for stable CAD.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •Age ≥ 18 years and < 75 years
- •Acute STEMI ≤ 12 h defined as
- •Angina or equivalent symptoms > 30 min and
- •ST elevation ≥ 2 leads (≥ 2 mm precordial leads, ≥ 1 mm limb leads) or ST depression ≥ 1 mm precordial leads in posterior MI
- •planned percutaneous coronary intervention
- •legal capacity
- •informed consent
- •first medical contact in the prehospital setting or in a non-PCI hospital (this criterion was changed by a protocol amendment in autumn 2012 to "first medical contact in the prehospital setting, in a non-PCI hospital, or in a PCI-hospital, if the expected time until the start of the scheduled PCI is at least 20 minutes")
排除标准
- •Age ≥ 75 years
- •Body weight < 60 kg
- •Thrombolytic therapy within 24 hours before randomization
- •Oral anticoagulation
- •Known hemorrhagic diathesis
- •History of Stroke or TIA
- •Cardiogenic shock
- •Evidence of an active gastrointestinal or urogenital bleeding
- •Major surgery within 6 weeks
- •Contraindication to prasugrel or clopidogrel
- •Severe renal or hepatic insufficiency
- •Contraindication to coronary angiography
- •Planned administration of a GP IIb/IIIa-Inhibitor before angiography
- •Pregnant or nursing (lactating) women
- •Patients currently (within the last 10 days) treated with clopidogrel, prasugrel, ticlopidine, or ticagrelor
- •Uncontrollable hypertension (blood pressure ≥ 200/110 mmHg in repeated measurements)
- •Treatment with NSAIDs
- •Participation in another clinical or device trial within the previous 30 days
- •First medical contact in a PCI-hospital (this criterion was changed by a protocol amendment in autumn 2012 to "Expected time between administration of loading dose and start of PCI is < 20 minutes")
研究组 & 干预措施
prasugrel
treatment with a 60 mg loading dose prasugrel, followed by a maintenance dose of 10 mg for 30 days
干预措施: Prasugrel (Drug)
clopidogrel
treatment with a 600 mg loading dose clopidogrel, followed by a maintenance dose of 75 mg for 30 days
干预措施: Clopidogrel (Drug)
结局指标
主要结局
platelet reactivity index (PRI) measured by VASP phosphorylation
时间窗: 2 hours after initiation of therapy
The primary endpoint is the platelet reactivity index (PRI) measured by VASP phosphorylation 2 hours after the initiation of the therapy. The VASP assay was chosen because it is not influenced by the concomitant administration of GP IIb/IIIa inhibitors, which are expected to be given in 50-60% of STEMI patients.
次要结局
- stroke (hemorrhagic, non-hemorrhagic)(day 30)
- TIMI 3 patency after PCI(2 hours after initiation of therapy)
- ST resolution immediately before angiography(1 hour after initiation of therapy)
- platelet reactivity index 4 hours after initiation of therapy(4 hours after initiation of therapy)
- rate of complete (> 70%) ST segment resolution 60 minutes after PCI as assessed by an ECG core laboratory which is blinded to the treatment group(60 min after PCI)
- partial or no ST resolution 60 minutes after PCI(60 minutes after PCI)
- ST segment deviation 60 minutes after PCI(60 minutes after PCI)
- death, re-MI, stent thrombosis and urgent revascularisation until 48 hours, day 7 and 30 days(48 hours, day 7, day 30)
- TIMI 2/3 patency of the infarct-related artery immediately prior to PCI done by an angiography core reading centre which is blinded to treatment group(1 hour after initiation of therapy)
- TIMI 3 patency before PCI(1 hour after initiation of therapy)
- severe bleeding complications according to the TIMI and GUSTO classifications(day 30)