Coronary Syndrome Clinical Trial
— WILLOW CCSOfficial title:
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?
Verified date | February 2024 |
Source | Sheffield Teaching Hospitals NHS Foundation Trust |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 48 |
Est. completion date | December 1, 2023 |
Est. primary completion date | August 31, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion 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 Exclusion Criteria: 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. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Sheffield Teaching Hospitals NHS Foundation Trust | Sheffield | South Yorkshire |
Lead Sponsor | Collaborator |
---|---|
Sheffield Teaching Hospitals NHS Foundation Trust |
United Kingdom,
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Task Force Members; Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ; ESC Committee for Practice Guidelines; Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013 Oct;34(38):2949-3003. doi: 10.1093/eurheartj/eht296. Epub 2013 Aug 30. No abstract available. Erratum In: Eur Heart J. 2014 Sep 1;35(33):2260-1. — View Citation
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* Note: There are 19 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Bleeding Time Difference | 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. | Until 14 (-2) days after last IMP dose | |
Secondary | Bleeding time pre-dose | A secondary endpoint will be the difference in bleeding time measured at pre-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Fibrin clot lag time by fibrin clot turbidimetry | A secondary endpoint will be the difference in fibrin clot lag time at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Fibrin clot lysis time by fibrin clot turbidimetry | A secondary endpoint will be the difference in fibrin lysis lag time at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Plasma TNF by enzyme-linked immunosorbent assay (ELISA)/multiplex bead assay (MBA) | A secondary endpoint will be the difference in Plasma TNF-a at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Plasma IL-6 by ELISA | A secondary endpoint will be the difference in Plasma IL-6 at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Serum CRP (Roche Cobas assay) | A secondary endpoint will be the difference in Serum CRP at 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Leukocyte count (and subsets), by automated cell counting | A secondary endpoint will be the difference in Leukocyte count at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Serum TXB2 by ELISA | A secondary endpoint will be the difference in Serum TXB2 at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Urine PGI-M by ELISA | A secondary endpoint will be the difference in Urine PGI-M at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Urine TxM by ELISA | A secondary endpoint will be the difference in Urine TxM at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Platelet aggregation responses to AA, collagen and adenosine diphosphate ADP by light transmittance aggregometry | Mean platelet aggregation responses to arachidonic acid (AA), collagen and adenosine diphosphate (ADP), at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose | |
Secondary | Final clot turbidity by fibrin clot turbidimetry | A secondary endpoint will be the final clot turbidity at pre-dose and 2 hours post-dose | Until 14 (-2) days after last IMP dose |
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