Acute coronary syndrome Circulatory System
Conditions
Interventions
Current interventions as of 05/09/2023:
The eligible participants in this study will be randomized at Visit 2 in a 50:50 manner to one of two arms using the online randomisation service sealedenvelope
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study-specific procedures 2. Male or female aged 18 years or over 3. Currently hospitalised for treatment of an acute coronary syndrome 4. Currently receiving aspirin 75 mg once daily 5. Current treatment or prior treatment during the current hospitalisation with ticagrelor 90 mg twice daily 6. Currently being considered for CABG surgery during the current hospitalisation following coronary angiography with plan to stop ticagrelor approximately 5 days before surgery
Exclusion criteria
Exclusion criteria: 1. CABG surgery planned to occur urgently either less than 3 days after cessation of ticagrelor or less than 5 days after cessation of ticagrelor without guidance by platelet function testing 2. Treatment within the last 7 days or planned treatment with any antiplatelet drug other than aspirin and ticagrelor (including prasugrel, clopidogrel, dipyridamole, cilostazol, or glycoprotein IIb/IIIa antagonists) except for a short course of a glycoprotein IIb/IIIa antagonist (tirofiban or eptifibatide) as bridging therapy in those discontinuing ticagrelor at least 3 days prior to scheduled CABG surgery 3. Current or planned treatment prior to CABG surgery with oral or parenteral anti-inflammatory/immunomodulatory drugs (oral corticosteroids; disease-modifying anti-rheumatic drugs, including methotrexate at any dose; immunosuppressants; chemotherapy drugs), oral anti-coagulant medications (warfarin, dabigatran, rivaroxaban, edoxaban, apixaban) or intravenous fibrinolytic agents 4. Current or planned treatment prior to CABG surgery with a non-steroidal anti-inflammatory drug other than aspirin 5. Known hypersensitivity to or intolerance of aspirin, salicylic acid (including certain asthma patients who may suffer an asthma attack or faint), ticagrelor or excipients 6. Clinically significant liver disease, defined as a 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 on blood tests performed during the current hospitalisation 7. Abnormal full blood count on blood tests performed during the current hospitalisation that, in the opinion of the investigator, would preclude safe involvement in the study or compromise its scientific credibility 8. Evidence of active pathological bleeding 9. Participants with clinically significant co-morbidity that, in the opinion of the investigator, would preclude safe involvement in the study or compromise its scientific credibility 10. Any clinically significant abnormal laboratory test results during the current hospitalisation that, in the opinion of the investigator, would preclude safe involvement in the study 11. Pregnant or breastfeeding women 12. Known haemorrhagic diathesis or coagulation disorders such as haemophilia or moderate or severe thrombocytopenia (platelet count 40 mg/day or CYP3A substrates with a narrow therapeutic index 15. Any other contraindication for ticagrelor or aspirin treatment as detailed in the respective SmPCs 16. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The absolute level of platelet aggregation in response to collagen 4ug/ml, measured using light transmittance aggregometry immediately following cardiopulmonary bypass | — |
Secondary
| Measure | Time frame |
|---|---|
| The two groups will be compared using the following outcomes, where 'pre-surgery' indicates the timepoint on the day of surgery prior to induction of anaesthesia: 1. Absolute light transmission aggregometry (LTA) response to arachidonic acid (AA) 1 mmol/L measured immediately post-CPB 2. Platelet reactivity units (PRU) and % inhibition values assessed using the VerifyNow P2Y12 assay immediately post-CPB 3. Increase in plasma IL-6 level, assessed using ELISA, from pre-surgery to immediately post-CPB 4. Increase in plasma D-dimer level, assessed using immunoturbidimetry, from pre-surgery to immediately post-CPB 5. Absolute skin bleeding time (in minutes) assessed using the bleeding time test immediately post-surgery 6. Total chest tube drainage recorded in millilitres from patient records from immediately post-surgery to 24 hours post-surgery The following outcomes will be assessed independently in each group: 1. Change in plasma ticagrelor concentration measured using mass spectrometry from pre-surgery to immediately post-CPB 2. Change in plasma ticagrelor active metabolite concentration measured using mass spectrometry from pre-surgery to immediately post-CPB | — |
Countries
England, United Kingdom
Contacts
Public ContactRobert Storey
Outcome results
None listed