Comparison of Analgesia With Fentanyl and Morphine on Platelet Inhibition After Pre-hospital Ticagrelor Administration in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU)
研究概览
简要总结
Prospective, randomized, open-label, single-center, investigator-initiated trial, including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) within 12 hours of the symptom's onset. The study aims to compare platelet inhibition (pharmacodynamics and pharmacokinetics) of pre-hospital Ticagrelor in patients with STEMI according to two different analgesia protocols using Fentanyl or Morphine.
详细描述
Consecutive patients with acute STEMI within 12 hours of the symptoms' onset and candidates for PPCI will be screened for inclusion in the study. Eligible patients who require analgesia for the relief of acute chest pain, defined as Visual Analogue Scale ≥3, will be randomized in a 1:1 ratio into one of the two treatment arms to receive analgesia with either Morphine or Fentanyl following administration of a pre-hospital loading dose of Ticagrelor. Randomized patients will undergo primary PCI and managed according to the current guidelines of the European Society of Cardiology. Blood samples (10 ml) will be collected at 0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor to assess platelet inhibition using the VerifyNow P2Y12 function and the Vasodilator-Stimulated-phosphoprotein Phosphorylation (VASP) assays, plasma concentration of Ticagrelor and its active metabolite (AR-C124910XX) using a validated liquid chromatography/mass spectrometry detection method and the procoagulant action of platelets.
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
- None
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
- •Age >18-year-old
- •STEMI within 12 hours of symptoms' onset eligible for primary PCI with stent implantation.
- •Patient able to give written informed consent.
排除标准
- •Contraindication, intolerance or hypersensitivity to Ticagrelor, or any excipients
- •Contraindication, intolerance or hypersensitivity to Morphine, Fentanyl, or any excipients
- •Active bleeding or bleeding diathesis
- •History of intracranial haemorrhage
- •Chronic oral anticoagulation treatment
- •Previous antiplatelet treatment
- •Contraindications to antiplatelet therapy
- •Severe renal insufficiency (creatinine clearance <30 mL/min)
- •Severe hepatic dysfunction
- •Severe chronic obstructive pulmonary disease
- •Periprocedural glycoprotein IIb/IIIa inhibitors administration
- •Relevant haematological disease
- •Patient who is currently, plans, or has been enrolled in another clinical study involving use of an investigational drug or device within the prior 30 days.
- •If female, patient pregnant or breastfeeding.
研究组 & 干预措施
Morphine
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Morphine (Drug)
Morphine
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Ticagrelor (Drug)
Morphine
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Aspirin (Drug)
Morphine
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Unfractioned Heparin (Drug)
Morphine
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Primary PCI (Procedure)
Fentanyl
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Fentanyl (Drug)
Fentanyl
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Ticagrelor (Drug)
Fentanyl
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Aspirin (Drug)
Fentanyl
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Unfractioned Heparin (Drug)
Fentanyl
- Pre-hospital Ticagrelor 180 mg loading dose orally.
- Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required.
- Aspirin 500 mg loading dose orally (or intravenously).
- Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.
- Primary PCI.
干预措施: Primary PCI (Procedure)
结局指标
主要结局
Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU)
时间窗: 2 hours after loading dose of Ticagrelor
次要结局
- Area under the plasma concentration-time curve of Ticagrelor(at 1, 2, 4, 6 and 12 hours)
- Peak plasma concentration (Cmax) of Ticagrelor and AR-C124910XX(at 1, 2, 4, 6 and 12 hours)
- Time to peak plasma concentration (tmax) of Ticagrelor and AR-C124910XX(at 1, 2, 4, 6 and 12 hours)
- Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography(at 2 hours)
- Residual PR by PRU(0, 1, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor)
- High on Treatment Platelet Reactivity (HTPR) rates(0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor)
- Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI(at 2 hours)
研究者
Dr Juan F. Iglesias, MD
MD
Centre Hospitalier Universitaire Vaudois