Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)
A Randomized, Double-blind Study Evaluating the Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor and Its Active Metabolite (AR-C124910XX) in Patients With ST-segment Elevation Myocardial Infarction and Non-ST-segment Elevation Myocardial Infarction.
研究概览
详细说明
The European Society of Cardiology and American Heart Association guidelines recommend use of morphine as a treatment of choice for pain relief in STEMI patients. However, this recommendation, although strong, is only based on expert consensus (class of recommendation I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the work of breathing and reduces anxiety. On the other hand, despite its favorable analgesic and sedative actions, morphine also exerts adverse effects, which include hypotension, bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility. Some of the previously listed morphine's side effects could affect the intestinal absorption and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting are available. Therefore, evidence-based verification of morphine's influence on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) could provide a valuable insight in the knowledge regarding modern acute myocardial infarction management.
Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration of ticagrelor and its active metabolite (AR-C124910XX).
Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients (15 patients for each arm) for estimating the final sample size.
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
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Kujawsko-pomorskie
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Bydgoszcz、Kujawsko-pomorskie、波兰、85-094
- Cardiology Department, Dr. A. Jurasz University Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- provision of informed consent prior to any study specific procedures
- diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction
- male or non-pregnant female, aged 18-80 years old
- provision of informed consent for angiography and PCI
Exclusion Criteria:
- chest pain described by the patient as unbearable or patient's request for analgesics
- prior morphine administration during the current STEMI or NSTEMI
- treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
- hypersensitivity to ticagrelor
- current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
- active bleeding
- history of intracranial hemorrhage
- recent gastrointestinal bleeding (within 30 days)
- history of coagulation disorders
- platelet count less than <100 x10^3/mcl
- hemoglobin concentration less than 10.0 g/dl
- history of moderate or severe hepatic impairment
- history of major surgery or severe trauma (within 3 months)
- patients considered by the investigator to be at risk of bradycardic events
- second or third degree atrioventricular block during screening for eligibility
- history of asthma or severe chronic obstructive pulmonary disease
- patient required dialysis
- manifest infection or inflammatory state
- Killip class III or IV during screening for eligibility
- respiratory failure
- history of severe chronic heart failure (NYHA class III or IV)
- concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
- body weight below 50 kg
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器:Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
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180 毫克负荷剂量
其他名称:
IV bolus injection
其他名称:
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安慰剂比较:Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
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180 毫克负荷剂量
其他名称:
IV bolus injection
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
大体时间:prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
大体时间:prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Maximum Concentration of Ticagrelor
大体时间:12 hours
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Maximum concentration (Cmax) of ticagrelor
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12 hours
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Maximum Concentration of AR-C124910XX
大体时间:12 hours
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Maximum concentration (Cmax) of AR-C124910XX
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12 hours
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Time to Maximum Concentration for Ticagrelor
大体时间:12 hours
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Time to maximum concentration (Tmax) for ticagrelor
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12 hours
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Time to Maximum Concentration for AR-C124910XX
大体时间:12 hours
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Time to maximum concentration (Tmax) for AR-C124910XX
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12 hours
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Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
大体时间:prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)
大体时间:prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:prior to the initial ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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prior to the initial ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:30 minutes post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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30 minutes post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:1 hour post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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1 hour post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:2 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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2 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:3 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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3 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:4 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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4 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:6 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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6 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
大体时间:12 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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12 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:prior to the initial ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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prior to the initial ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:30 minutes post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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30 minutes post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:1 hour post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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1 hour post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:2 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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2 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:3 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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3 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:4 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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4 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:6 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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6 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
大体时间:12 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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12 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:prior to the initial ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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prior to the initial ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:30 minutes post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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30 minutes post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:1 hour post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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1 hour post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:2 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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2 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:3 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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3 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:4 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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4 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:6 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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6 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
大体时间:12 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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12 hours post ticagrelor dose
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
大体时间:2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP
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2 hours
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA
大体时间:2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
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2 hours
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
大体时间:2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow
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2 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP
大体时间:12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
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12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
大体时间:12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
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12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
大体时间:12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
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12 hours
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合作者和调查者
调查人员
- 首席研究员:Prof. Jacek Kubica, MD, PhD、Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
出版物和有用的链接
一般刊物
- Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, Stankowska K, Buszko K, Navarese EP, Jilma B, Siller-Matula JM, Marszall MP, Rosc D, Kozinski M. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016 Jan 14;37(3):245-52. doi: 10.1093/eurheartj/ehv547. Epub 2015 Oct 21.
- Kubica J, Adamski P, Ostrowska M, Kozinski M, Obonska K, Laskowska E, Obonska E, Grzesk G, Winiarski P, Paciorek P. Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a randomized controlled trial. Trials. 2015 Apr 29;16:198. doi: 10.1186/s13063-015-0724-z.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- CMUMK202
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
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