Myocardial Infarction
Conditions
Keywords
extracellular vesicles, inflammation, thrombosis, antiplatelet drugs
Brief summary
Platelet activation and aggregation leads to myocardial infarction. Platelet P2Y12 receptors are essential for platelet activation. Antagonists against the P2Y12 receptor, which are established in secondary prevention of myocardial infarction, have unexplained anti-inflammatory effects. A novel P2Y12 receptor antagonist ticagrelor reduced infection-related mortality compared to clopidogrel, previous standard treatment for patients with myocardial infarction. Activated platelets release pro-inflammatory and procoagulant platelet extracellular vesicles. The investigators assume that decrease in infection-related mortality in patients treated with ticagrelor may be explained by greater inhibition of the release of platelet vesicles by ticagrelor, compared to clopidogrel. This study is expected to identify an additional mechanism of action of ticagrelor, which might contribute to the observed clinical benefits in patients treated with ticagrelor.
Interventions
DRUGTicagrelor
Comparison of ticagrelor with another antiplatelet drug (clopidogrel)
DRUGClopidogrel
Comparison of clopidogrel with another antiplatelet drug (ticagrelor)
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Medical University of Warsaw
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age \> 18 years * Informed consent to participate in the study * Percutaneous coronary intervention with stent implantation due to first S T elevation myocardial infarction, or first non S T -elevation myocardial infarction * Administration of a loading dose of clopidogrel
Exclusion criteria
* Known coagulopathy * Known history of bleeding disorder * Suspicion of intracranial haemorrhage * Need for oral anticoagulation therapy * Administration of glycoprotein (GP) II b - III a antagonists * Cardiogenic shock * Severe chronic renal failure (estimated glomerular filtration rate \< 30 mL/min) * Severe liver insufficiency * Chronic dyspnea * Increased risk of bradycardia * Autoimmune disease * Infectious disease * Neoplasms * Pregnancy * Study drug intolerance * Co-administration of ticagrelor or clopidogrel with strong CYP3A4 inhibitors * Participation in any previous study with ticagrelor or clopidogrel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Platelet Extracellular Vesicles/ml | 6 months following the beginning of antiplatelet therapy | Concentration of platelet extracellular vesicles/ml measured with flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Extracellular Vesicles Exposing Fibrinogen | 6 months | Concentration of extracellular vesicles exposing fibrinogen/ ml measured with flow cytometry |
| Concentration of Extracellular Vesicles Exposing Phosphatidylserine | 6 months | Concentration of extracellular vesicles exposing phosphatidylserine/ml measured with flow cytometry |
| Concentration of Extracellular Vesicles From Endothelial Cells | 6 months | The concentrations of extracellular vesicles from endothelial cells/ ml measured with flow cytometry |
| Concentration of Extracellular Vesicles From Leukocytes | 6 months | Concentration of extracellular vesicles from leukocytes/ ml measured with flow cytometry |
Countries
Netherlands, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose) | 30 |
| Clopidogrel Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose) | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Clopidogrel | Total | Ticagrelor |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 25 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 35 Participants | 19 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Poland | 30 participants | 60 participants | 30 participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 24 Participants | 46 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 1 / 30 | 1 / 30 |
Outcome results
Primary
Concentration of Platelet Extracellular Vesicles/ml
Concentration of platelet extracellular vesicles/ml measured with flow cytometry
Time frame: 6 months following the beginning of antiplatelet therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ticagrelor | Concentration of Platelet Extracellular Vesicles/ml | 2690000 Platelet Extracellular Vesicles/mL |
| Clopidogrel | Concentration of Platelet Extracellular Vesicles/ml | 4310000 Platelet Extracellular Vesicles/mL |
Secondary
Concentration of Extracellular Vesicles Exposing Fibrinogen
Concentration of extracellular vesicles exposing fibrinogen/ ml measured with flow cytometry
Time frame: 6 months
Secondary
Concentration of Extracellular Vesicles Exposing Phosphatidylserine
Concentration of extracellular vesicles exposing phosphatidylserine/ml measured with flow cytometry
Time frame: 6 months
Secondary
Concentration of Extracellular Vesicles From Endothelial Cells
The concentrations of extracellular vesicles from endothelial cells/ ml measured with flow cytometry
Time frame: 6 months
Secondary
Concentration of Extracellular Vesicles From Leukocytes
Concentration of extracellular vesicles from leukocytes/ ml measured with flow cytometry
Time frame: 6 months