Characterisation of a Novel Regimen of Very Low-dose Aspirin Combined With Rivaroxaban in Patients With Chronic Coronary Syndromes: WILL lOWer Dose Aspirin be Better With Rivaroxaban in Patients With Chronic Coronary Syndromes?
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Bleeding Time Difference
研究概览
简要总结
The trial is a pharmacodynamic study to determine the effect of a novel regimen of aspirin 20 mg BD plus rivaroxaban 2.5 mg BD on haemostasis, fibrin clot dynamics, inflammatory markers, platelet function and arachidonic acid metabolites when compared to standard regimens of aspirin 75 mg OD and aspirin 75 mg OD plus rivaroxaban 2.5 mg BD.
In a randomised open-label three-period crossover design, patient participants receiving aspirin 75 mg OD for secondary prevention of IHD will be randomised 1:1 to receive one of two sequences of aspirin: aspirin 75 mg OD, then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD, then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD; or aspirin 75 mg OD, then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD, then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD.
At the end of each 14(-2) day medication period, they will attend a study visit at which blood and urine samples will be obtained, and bleeding time measured, before and 2 hours after the last dose of IMP of the treatment period. The samples will be tested for fibrin clot dynamics; inflammatory markers and cytokines; prostanoids; and platelet function.
Participants will be transitioned back to standard-of-care aspirin 75 mg OD at the end of the third treatment period and followed up by telephone call 14(-2) days later.
详细描述
Recruitment Potential participants will be identified through review of the records of the South Yorkshire Cardiothoracic Centre and/or by referral by their clinical team.
Specifically, participants may be approached in the following ways:
- An invitation letter sent by post in combination with a copy of the participant information sheet. There will be a reply slip which they can return by post, and there will be contact details (telephone and email) for the research team to allow them to respond by these methods too.
- Directly by telephone. In this case, should they be happy to learn more, they will be sent a copy of the invitation letter, participant information sheet and reply slip by post or email, depending on their preference. If they agree to attend for study screening, they will communicate this to the research team by returning the reply slip by post or email, or by contacting the research team directly using the contact details provided to them.
- Directly in clinics within the Cardiology and Cardiothoracic Surgery Directorate at Sheffield Teaching Hospitals NHS Foundation Trust, upon referral from their clinical team. In this case they will be provided with a copy of the participant information sheet and, if unable to decide whether they wish to attend for screening or not during the clinic visit, will be signposted to the contact details of the research team to provide their response.
Potential participants who are interested in taking part in the study will then be contacted by the research team to book a screening appointment.
Screening
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •Provision of informed consent prior to any study specific procedures
- •Male or female aged greater than 18 years
- •Existing diagnosis of a chronic coronary syndrome:
- •(i) History of stable angina or (ii) History of an acute coronary syndrome event >1 year ago or (iii) Previous evidence on imaging of either at least one stenosis >50% in an epicardial coronary artery or a myocardial perfusion defect
- •Receiving single antiplatelet therapy with aspirin 75 mg once daily
排除标准
- •Any history of haemorrhagic stroke or lacunar stroke
- •History of ischaemic stroke or transient ischaemic attack in the last year
- •Heart failure associated with NYHA class III or IV symptoms
- •Estimated glomerular filtration rate <15 ml/min
- •Planned procedure for coronary revascularization
- •Any planned surgery or other procedure that may require suspension or discontinuation of antiplatelet therapy expected to occur within 3 months of randomisation
- •Prior intention by patient or physician to discontinue aspirin within the study period
- •Receiving doses of aspirin other than 75 mg once daily
- •Treatment or planned treatment with antiplatelet medication apart from aspirin (eg. clopidogrel, prasugrel, ticagrelor, dipyridamole, ticlopidine)
- •Current use of a loop, thiazide or potassium sparing diuretic (affects prostanoid assays)
- •Any acute coronary syndrome event, percutaneous coronary intervention or coronary artery bypass grafting within 1 year prior to randomisation
- •Current or planned use of an oral anticoagulant (e.g. warfarin, dabigatran, rivaroxaban [including 2.5 mg BD], apixaban, edoxaban) or parenteral anticoagulant (eg. unfractionated heparin, low molecular weight heparin, bivalirudin)
- •Current or planned use of a GPIIb/IIIa inhibitor (eg. abciximab, tirofiban)
- •Current or planned use of a fibrinolytic agent (eg. tissue plasminogen activator)
- •Requiring or likely to require treatment with a non-steroidal anti-inflammatory drug (NSAID), including COX2 inhibitors, and including regular or intermittent/as required use
- •Current or planned use of a strong CYP3A4 inhibitor (eg, ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin [but not erythromycin or azithromycin], nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, cobicistat or over 1 litre daily of grapefruit juice), strong inducer (e.g. rifampin/rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital), a selective serotonin reuptake inhibitor (SSRI) or selective noradrenergic reuptake inhibitor (SNRI).
- •Clinically significant liver disease, defined as known or suspected diagnosis of hepatic cirrhosis with current Child Pugh class B or C; or elevation of serum alanine transferase or aspartate transferase greater than 3 times the upper limit of the normal range for the processing laboratory.
- •History of alcohol or drug abuse, defined as regular use of an illicit substance for recreational purposes or regular consumption of greater than 50 units (males) or 35 units (females) of alcohol per week, in the last year
- •Co-morbidity associated with life expectancy less than 1 year
- •Any other condition deemed by the investigator to significantly affect haemostasis, coagulation, bleeding risk or ability to comply with the study protocol.
- •Females of child-bearing potential unless negative pregnancy test at screening and willing to use effective contraception (i.e. established use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or barrier methods of contraception with spermicide or sole male partner with prior vasectomy and confirmed absence of sperm in ejaculate) for the duration of treatment with study medication.
研究组 & 干预措施
Aspirin 20mg
Aspirin 75 mg OD for 14(-2) days then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD for 14(-2) days then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD
干预措施: Aspirin 75mg (Drug)
Aspirin 20mg
Aspirin 75 mg OD for 14(-2) days then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD for 14(-2) days then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD
干预措施: Aspirin 20mg (Drug)
Aspirin 20mg
Aspirin 75 mg OD for 14(-2) days then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD for 14(-2) days then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD
干预措施: Rivaroxaban 2.5 mg (Drug)
Asprin 75mg
Aspirin 75 mg OD for 14(-2) days then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD for 14(-2) days then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD
干预措施: Aspirin 75mg (Drug)
Asprin 75mg
Aspirin 75 mg OD for 14(-2) days then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD for 14(-2) days then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD
干预措施: Aspirin 20mg (Drug)
Asprin 75mg
Aspirin 75 mg OD for 14(-2) days then aspirin 75 mg OD plus rivaroxaban 2.5 mg BD for 14(-2) days then aspirin 20 mg BD plus rivaroxaban 2.5 mg BD
干预措施: Rivaroxaban 2.5 mg (Drug)
结局指标
主要结局
Bleeding Time Difference
时间窗: after 14(-2) days on each treatment schedule, bleeding time (seconds) performed 2 hours after the latest dose of aspirin +/- rivaroxaban.
The primary endpoint will be difference in bleeding time, measured at 2 hours post-dose, assessed between aspirin (aspirin lysine) 75 mg once-daily alone vs. aspirin (aspirin lysine) 20 mg twice-daily plus rivaroxaban 2.5 mg twice-daily and aspirin (aspirin lysine) 75 mg once-daily alone vs. aspirin (aspirin lysine) 75 mg once-daily plus rivaroxaban 2.5 mg twice-daily.
次要结局
未报告次要终点