Chronic coronary syndrome MedDRA version: 20.0 Level: PT Classification code 10011078 Term: Coronary artery disease System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Xarelto 2.5 mg film-coated tablets
Product Name: Xarelto 2.5 mg film-coated tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Rivaroxaban
CAS Number: 366789-02-8
Concentration unit:
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study, subjects should fulfil the following criteria: 1. Provision of informed consent prior to any study specific procedures 2. Male or female aged greater than 18 years 3. 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 4. Receiving single antiplatelet therapy with aspirin 75 mg once daily Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from participation in the study: 1. Any history of haemorrhagic stroke or lacunar stroke 2. History of ischaemic stroke or transient ischaemic attack in the last year 3. Heart failure associated with NYHA class III or IV symptoms 4. Estimated glomerular filtration rate <15 ml/min 5. Planned procedure for coronary revascularization 6. Any planned surgery or other procedure that may require suspension or discontinuation of antiplatelet therapy expected to occur within 3 months of randomisation 7. Prior intention by patient or physician to discontinue aspirin within the study period 8. Receiving doses of aspirin other than 75 mg once daily 9. Treatment or planned treatment with antiplatelet medication apart from aspirin (eg. clopidogrel, prasugrel, ticagrelor, dipyridamole, ticlopidine) 10. Current use of a loop, thiazide or potassium sparing diuretic (affects prostanoid assays) 11. Any acute coronary syndrome event, percutaneous coronary intervention or coronary artery bypass grafting within 1 year prior to randomisation 12. 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) 13. Current or planned use of a GPIIb/IIIa inhibitor (eg. abciximab, tirofiban) 14. Current or planned use of a fibrinolytic agent (eg. tissue plasminogen activator) 15. 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 16. 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). 17. 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. 18. 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 19. Co-morbidity associated with life expectancy less than 1 year 20. Any other condition deemed by the investigator to significantly affect haemostasis, coagulation, bleeding risk or ability to comply with the study protocol. 21. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess, in patients with a history of chronic coronary syndromes (CCS) currently receiving aspirin 75 mg once-daily as anti-thrombotic therapy, the effects of a novel regimen of very-low-dose twice-daily aspirin (20 mg twice-daily) and rivaroxaban (2.5 mg twice-daily), compared to the standard regimens of aspirin therapy (75 mg once-daily), with or without rivaroxaban (2.5 mg twice-daily), on bleeding time, a surrogate marker of bleeding risk. Our principal hypothesis is that the difference in bleeding time between the aspirin 75 mg once-daily and aspirin 20 mg twice-daily plus rivaroxaban periods will be significantly lower than between the aspirin 75 mg once-daily and aspirin 75 mg once-daily plus rivaroxaban periods. ;Secondary Objective: The secondary objectives of this study are to compare the effect of the three different treatment regimens on fibrin clot dynamics (formation and breakdown), inflammatory parameters, platelet function and prostanoid levels (substances affected by aspirin).;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: At 14 days after commencing each study treatment regimen. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): When receiving aspirin (aspirin lysine) 20 mg BD plus rivaroxaban, vs. aspirin (aspirin lysine) 75 mg OD, vs. aspirin (aspirin lysine) 75 mg OD plus rivaroxaban 2.5 mg BD: 1. Bleeding time pre-dose 2. Fibrin clot lag time pre-dose and 2 hours post-dose 3. Fibrin clot lysis time pre-dose and 2 hours post-dose 4. Plasma TNF-a pre-dose and 2 hours post-dose 5. Plasma IL-6 pre-dose and 2 hours post-dose 6. Serum CRP 2 hours post-dose 7. Leukocyte count pre-dose and 2 hours post-dose 8. Serum TXB2 pre-dose and 2 hours post-dose 9. Urine PGI-M pre-dose and 2 hours post-dose 10. Urine TxM pre-dose and 2 hours post-dose 11. Mean platelet aggregation responses to arachidonic acid (AA), collagen and adenosine diphosphate (ADP), pre-dose and 2 hours post-dose 12. Final clot turbidity pre-dose and 2 hours post-dose Secondary endpoints will be compared between the three groups by repeated-measures ANOVA (1,2) and paired t-tests (3-9), where appropriate, between: 1. Post-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. post-dose (aspirin 75 mg OD) vs. post-dose (aspirin 75 mg OD plus rivaroxaban 2.5 mg BD) 2. Pre-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. pre-dose (aspirin 75 mg OD) vs. pre-dose (aspirin 75 mg OD plus rivaroxaban 2.5 mg BD) 3. Pre-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. post-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) 4. Pre-dose (aspirin 75 mg OD) vs. post-dose (aspirin 75 mg OD) 5. Pre-dose (aspirin 75 mg OD plus rivaroxaban 2.5 mg BD) vs. post-dose (aspirin 75 mg OD plus rivaroxaban 2.5 mg BD) 6. Post-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. post-dose (aspirin 75 mg OD) 7. Post-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. post-dose (aspirin 75 mg OD plus rivaroxaban 2.5 mg BD) 8. Pre-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. pre-dose (aspirin 75 mg OD) 9. Pre-dose (aspirin 20 mg BD plus rivaroxaban 2.5 mg BD) vs. pre-dose (aspirin 75 mg OD plus rivaroxaban 2. | — |
Countries
United Kingdom
Contacts
Public ContactJemima Clarke
Sheffield Teaching Hospitals NHS Foundation Trust
Outcome results
None listed