OraL Crushed and dIspersed Ticagrelor 180mg Compared to Whole Tablets of eQUal Dose in STEMI Patients unDergoing Primary PCI: a Pharmacokinetic/Pharmacodynamic Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Area under the ticagrelor plasma concentration versus time curve (AUC0-1) over 1 hour post ticagrelor administration
研究概览
简要总结
This is a single-center, prospective, randomized, single-blind, investigator initiated, pharmacokinetic/pharmacodynamic study of parallel design.Patients with ST elevation myocardial infarction (symptom onset<12 hours), undergoing primary percutaneous coronary intervention, who are P2Y12 inhibitor naïve, will be randomized after informed consent, immediately after diagnostic coronary angiography, in a 1:1 ratio to either:
- Ticagrelor 180mg loading dose, in the form of 2 whole tablets administered per os in the supine position (standard administration)
- Ticagrelor 180mg loading dose, in the form of 2 tablets crushed and dispersed in purified water and administered per os with 1-minute-stay in a 60-70 degrees semi-upright sitting position Platelet reactivity assessment will be performed at randomization (Hour 0) and at 0.5, 1, 2, 4 and 6 hours after randomization, using the VerifyNow assay, in platelet reactivity units (PRU). The cutoff >208 PRU will be used for definition of high platelet reactivity (HPR). All platelet reactivity assessments will be performed by a physician blind to the actual treatment given. Additional blood samples will be collected at the same time points for pharmacokinetic analysis. These samples will be collected in vacuum tubes with lithium heparin and will be kept in ice until centrifugation (3000 rpm at 4°C for 10 min, within 30 min of sampling). The resultant plasma will be transferred into a plain polypropylene tube (screw cap) and stored at or below -20°C until analysed.
详细描述
Preparation of Ticagrelor liquid formulation:
Crushed and dispersed Ticagrelor 180mg for oral administration will be prepared as follows: two ticagrelor 90mg tablets are placed in a mortar and crushed for 60 s using a pestle. 20 mL of purified water will be added in the mortar and stirred for 60s. The liquid is transferred to a dosing cup and another 15 mL of purified water is added to the mortar and stirred, ensuring that all powder has been dispersed and none remained on the mortar and pestle. Again the liquid is transferred to the dosing cup. The same procedure is repeated with 15 ml of purified water.The total contents are stirred for another 30 s to ensure that all remaining tablet particles are dispersed.
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 (Outcomes Assessor)
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 years old
- •Patients with STEMI (onset of pain<12 hours) with indication for primary PCI
- •Informed consent obtained in writing
排除标准
- •Pregnancy/Breastfeeding
- •Severe nausea or vomiting
- •Treatment with a P2Y12 inhibitor within the previous 1 month
- •Inability to give informed consent
- •Hemodynamic instability
- •Arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents
- •Killip class ≥3
- •Known hypersensitivity to ticagrelor
- •History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months.
- •Other bleeding diathesis, or considered by investigator to be at high risk for bleeding
- •Thombocytopenia (<100.000 / μL) at randomization
- •Anaemia (Hct <30%) at randomization
- •Polycytaemia (Hct > 52%) at randomization
- •Periprocedural IIb/IIIa inhibitor administration
- •Thrombolysis administration
- •Recent (< 6 weeks) major surgery or trauma, including GABG.
- •Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin /rifampicin, phenytoin, carbamazepine).
- •Patients considered by the investigator to be at increased risk of bradycardiac events.
- •Dialysis required.
- •Severe uncontrolled chronic obstructive pulmonary disease
- •Known severe hepatic impairement
研究组 & 干预措施
Ticagrelor 180mg whole tablets
Ticagrelor 180mg loading dose, in the form of 2 whole tablets administered per os in the supine position (standard administration)
干预措施: Ticagrelor 180mg whole tablets (Drug)
Ticagrelor 180mg crushed and dispersed
Ticagrelor 180mg in the form of 2 tablets crushed and dispersed in purified water administered per os with 1-minute-stay in a 60-70 degrees semi-upright sitting position
干预措施: Ticagrelor 180mg crushed and dispersed (Drug)
结局指标
主要结局
Area under the ticagrelor plasma concentration versus time curve (AUC0-1) over 1 hour post ticagrelor administration
时间窗: 1 hour
Ticagrelor's Cmax over 1 hour post ticagrelor administration
时间窗: 1 hour
次要结局
- Platelet reactivity at 1 hour post randomization(1 hour)
- HPR rate at 1 hour post randomization(1 hour)
- Platelet reactivity at 2 hours post randomization(2 hours)
- HPR rate at 2 hours post randomization(2 hours)
- AR-C124910XX Cmax over 1 hour post ticagrelor administration(1 hour)
- AR-C124910XX Cmax over 6 hours post ticagrelor administration(6 hours)
- Ticagrelor Cmax over 6 hours post ticagrelor administration(6 hours)
- Area under the AR-C124910XX plasma concentration versus time curve (AUC0-1) over 1 hour post ticagrelor administration(1 hour)
- Time for the maximum plasma concentration (Tmax) of Ticagrelor over 6 hours post Ticagrelor administration(6 hours)
- Time for the maximum plasma concentration (Tmax) of AR-C124910XX over 6 hours post Ticagrelor administration(6 hours)
- Area under the AR-C124910XX plasma concentration versus time curve (AUC0-6) over 6 hours post ticagrelor administration(6 hours)
- Area under the Ticagrelor plasma concentration versus time curve (AUC0-6) over 6 hours post ticagrelor administration(6 hours)
研究者
Dimitrios Alexopoulos
Professor of Cardiology
University of Patras