Percutaneous coronary intervention with stenting in patients with atrial fibrillation Circulatory System
Conditions
Interventions
The trial is a pharmacodynamic study to determine the effect of reduced-dose apixaban 2.5 mg BD with ticagrelor 90 mg BD on haemostasis, fibrin clot dynamics and platelet function compared to the stan
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study-specific procedures. 2. Male or female aged greater than 18 years. 3. PCI within the last 7 days for treatment of an acute or chronic coronary syndrome. 4. Current or previous atrial fibrillation for which long-term oral anticoagulation is indicated. 5. Receiving, or prescribed by the clinical care team to start receiving, apixaban 5 mg BD and ticagrelor 90 mg BD as DAT without aspirin.
Exclusion criteria
Exclusion criteria: 1. At least two out of the three following criteria for approved use of the apixaban 2.5 mg BD dose for prevention of stroke and systemic embolism in non-valvular atrial fibrillation: (i) age =80 years; (ii) body weight =60 kg; (iii) serum creatinine =133 umol/L. 2. Active clinically significant bleeding 3. Any history of haemorrhagic stroke or other intracranial haemorrhage 4. Estimated glomerular filtration rate <30 ml/min 5. Any planned surgery or other procedure expected to occur within 1 month of randomisation that may require suspension or discontinuation of apixaban or ticagrelor therapy 6. Prior intention by patient or physician to discontinue apixaban or ticagrelor within the study period 7. Planned treatment following randomization with antiplatelet medication apart from ticagrelor (e.g. aspirin, clopidogrel, prasugrel, dipyridamole, ticlopidine) 8. Planned treatment following randomization with an oral anticoagulant apart from apixaban (e.g. warfarin, dabigatran, rivaroxaban, edoxaban) or parenteral anticoagulant (e.g. unfractionated heparin, low-molecular-weight heparin, bivalirudin) except for short-term parenteral anticoagulation required to cover a staged or urgent vascular procedure 9. Current or planned use of a GPIIb/IIIa inhibitor (e.g. tirofiban) 10. Current or planned use of a fibrinolytic agent (e.g. tissue plasminogen activator) 11. Requiring or likely to require treatment with an oral non-steroidal anti-inflammatory drug (NSAID), including regular or intermittent/as required use except for intermittent use of topical preparations that are not expected to have measurable systemic effect 12. 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) or strong CYP3A4 inducer (e.g. rifampin/rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital). 13. Clinically significant liver disease, defined as known or suspected diagnosis of hepatic cirrhosis with current Child Pugh class B or C; or known elevation of serum alanine transferase or aspartate transferase greater than 3 times the upper limit of the normal range for the processing laboratory. 14. 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 15. Co-morbidity associated with life expectancy less than 3 months 16. Any other condition deemed by the investigator to significantly affect ability to comply with the study protocol. 17. Women of child-bearing potential (WOCBP) unless negative pregnancy test at screening and willing to use highly-effective contraception for the duration of treatment with study medication. 18. Pregnant or breast-feeding women. 19. Any contraindication for apixaban or ticagrelor treatment as detailed in the respective SmPCs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Bleeding time test (time taken for bleeding from small puncture wound to stop, measured in seconds) at 28(-2) days following randomisation and 2-4 hours post dose on the day of the test | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Fibrin clot lag time post-dose – measured via blood sample for laboratory analysis, taken 2-4 hours post dose at visit 3 2. Final clot turbidity post-dose – measured via blood sample for laboratory analysis, taken 2-4 hours post dose at visit 3 3. Fibrin clot lysis time post-dose – measured via blood sample for laboratory analysis, taken 2-4 hours post dose at visit 3 4. Platelet aggregation responses to tissue factor, ADP, AA, and collagen post-dose – measured via blood sample for laboratory analysis, taken 2-4 hours post dose at visit 3 5. Serum thromboxane B2 level – measured via blood sample for laboratory analysis taken 2-4 hours post dose, at visit 3 | — |
Countries
United Kingdom
Contacts
Public Contact. Clinical Research & Innovation Office
Outcome results
None listed