Clinical trial NCT02931045: Antiplatelet Therapy Effect on Extracellular Vesicles in Acute Myocardial Infarction
Official title: Antiplatelet Therapy Effect on Platelet Extracellular Vesicles in Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: extracellular vesicles
inflammation
thrombosis
antiplatelet drugs
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2016-10-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Concentration of Platelet Extracellular Vesicles/ml
timeFrame: 6 months following the beginning of antiplatelet therapy
Secondary outcomes:
measure: Concentration of Extracellular Vesicles Exposing Fibrinogen
timeFrame: 6 months
measure: Concentration of Extracellular Vesicles Exposing Phosphatidylserine
timeFrame: 6 months
measure: Concentration of Extracellular Vesicles From Endothelial Cells
timeFrame: 6 months
measure: Concentration of Extracellular Vesicles From Leukocytes
timeFrame: 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Laboratory of Experimental Clinical Chemistry, Academic Medical Centre of the University of Amsterdam
city: Warsaw
country: Poland
facility: 1st Chair and Department of Cardiology, Medical University of Warsaw
Study officials:
affiliation: 1st Chair and Department of Cardiology, Medical University of Warsaw
name: Aleksandra Gasecka, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gasecka A, Nieuwland R, van der Pol E, Hajji N, Cwiek A, Pluta K, Konwerski M, Filipiak KJ. P2Y12 antagonist ticagrelor inhibits the release of procoagulant extracellular vesicles from activated platelets. Cardiol J. 2019;26(6):782-789. doi: 10.5603/CJ.a2018.0045. Epub 2018 Apr 19.