A Single Center Phase II Assessor-Blinded RaNdomised Active Controlled Parallel-Group Trial to COmpare Ticagrelor Versus Clopidogrel on the REduction of ArteriaL STiffness and Wave Reflections in Patients With CoronarY Artery Disease.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Mean Change in the cfPWV
研究概览
简要总结
The purpose of this study is to investigate the potential acute and chronic effect of ticagrelor versus clopidogrel on arterial stiffness and other vascular risk markers of interest, the study will consist of two periods: a 24-hour ACUTE period where 60 subjects with an indication for coronary angiography (CA) with or without percutaneous coronary intervention (PCI) will be included, and a 30-day CHRONIC period where approximately 60 subjects that will undergo PCI will be included and studied (refer to Section 3 'Study Plan and Procedures'). The primary objective of this study is to compare ticagrelor versus clopidogrel regarding their effect on arterial stiffness as assessed by PWV, at 3 hours after the loading dose of each regimen, in eligible subjects with CAD.
详细描述
This is singe-center, randomized, assessor-blinded, active controlled, parallel-group trial consisting of an 'acute' and a 'chronic' period, aiming at comparing ticagrelor versus clopidogrel on the reduction of arterial stiffness and wave reflections in patients with CAD. This Investigator-Sponsored Study (ISS) will be supported by AstraZeneca.
60 subjects fulfilling all study-specific eligibility criteria will be initially recruited for the 'acute' study period of 24-hour duration. Subjects that will undergo ad hoc PCI will continue in the subsequent 'chronic' study period of 30-day duration.
In order to have 60 subjects in the 'chronic' study period (since some of the 'acute' period will not undergo PCI), additional subjects that are scheduled for elective PCI will be recruited until the sample size of 'chronic' study period reaches 60 subjects.
The study periods [Figure 1, Flow Chart] have as follows:
For the 24-hour ACUTE period, 60 subjects with an indication for elective CA with or without PCI will be included in the study.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study specific procedures.
- •Male and female subjects > 18 and < 79 years of age.
- •Indication for elective coronary angiography (angina, positive stress test/SPECT/stress echo) with or without PCI for inclusion in the 'acute' study period, and indication for either ad hoc or elective PCI for inclusion in the 'chronic' study period.
排除标准
- •Who had ACS within 12 months of screening.
- •Previous stent implantation with dual antiplatelet therapy within 12 months of screening.
- •Subjects being treated with anti-platelet medications other than aspirin prior to diagnostic catheterization including glycoprotein IIb/IIIa inhibitors.
- •Subjects with NYHA class III or IV heart failure or known left ventricular ejection fraction < 30%.
- •Subjects with hemodynamic or electrical instability (including shock).
- •History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 6 months.
- •Other bleeding diathesis, or considered by Investigator to be at high risk for bleeding.
- •Any previous history of ischemic or hemorrhagic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
- •International Normalized Ratio (INR) known to be >1.5 within 1 week of study entry.
- •Poorly controlled blood pressure (>160/100 mmHg).
- •Known platelet count of <100,000/mm3 within 1 week of study entry.
- •Known anemia (hemoglobin [Hb] <10 gr/dL) within 1 week of study entry.
- •Subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.
- •Severe kidney disease (GFR<30 ml/min/1.73m2).
- •Hepatic insufficiency defined as liver cirrhosis, AST/ALT/Alkaline Phosphatase greater than 3 times the upper limit of normal or hyperbilirubinemia defined as peak total serum bilirubin greater than 2 times the upper limit of normal (ULN).
- •Any indication (atrial fibrillation, mitral stenosis or prosthetic heart valve, pulmonary embolism (PE), deep vein thrombosis (DVT)) for anticoagulation treatment during study period.
- •Asthma or chronic obstructive pulmonary disease requiring brochodilating agents.
- •Concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inhibitors (atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) or inducers (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, and rifapentine).
- •Concomitant use of drugs that are metabolized through CYP2C19 (omeprazole and esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine and chloramphenicol).
- •History of uric acid nephropathy and high levels of uric acid within 1 week of study entry.
- •Increased risk of bradycardic events (e.g. known sick sinus syndrome or third degree AV block or previous documented syncope suspected to be due to bradycardia unless treated with a pacemaker).
- •Known neoplastic or autoimmune disease or any concomitant medical illness that in the opinion of the Investigator may interfere with or prevent completion in this study.
- •Contraindication to clopidogrel, ASA, or ticagrelor.
- •A history of alcohol and/or substance abuse that could interfere with conduct of the trial.
- •Pregnancy or lactation (for premenopausal women 2 methods of reliable contraception, one of which must be barrier method, are required).
- •Treatment with other investigational agents (including placebo) or devices within 30 days prior to randomization or planned use of investigational agents or devices prior to the Day 30 visit.
- •Life expectancy less than 1 year.
- •Indication for major surgery (e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery).
- •High likelihood of being unavailable for the Day 30 follow up.
研究组 & 干预措施
Clopidogrel
Loading dose 600 mg .Mainatinance dose 75 mg QD
干预措施: Ticagrelor (Drug)
Ticagrelor
Loading dose 180 mg . Maintenance 90 mg BID
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Mean Change in the cfPWV
时间窗: at 3 hours after the loading dose
The primary outcome is the treatment difference in the mean change in cfPWV from baseline (0 hours) at 3 hours after the loading dose of each regimen, in ticagrelor and clopidogrel acute period populations.
次要结局
- mean change in the cfPWV(from baseline at 24 hours after the loading dose)