• To investigate the magnitude and time course of platelet reactivity and platelet activation in patients with a STEMI undergoing primary percutaneous coronary intervention (pPCI).• To investigate the magnitude and time course of thrombin generation…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Platelet function tests, including LTA, VerifyNow P2Y12, TEG, Multiplate, PFA
(see appendix A)
• Percentage platelet bound P-selectin expression (see appendix A)
• Thrombin generation at high tissue factor concentration, at low tissue factor
concentration and with microparticle reagens.
• Coagulation factors: Full length tissue factor pathway inhibitor (FL-TFPI),
total protein S, FVIII, vWF
• Genetic variations associated with response to antiplatelet therapy and
thrombus formation
Secondary outcome
nvt
Background summary
Platelets play a pivotal role in the pathogenesis of atherosclerosis and
thrombus formation, which contributes to the development of acute ischemic
coronary events. (1,2) Therefore, dual antiplatelet therapy with aspirin and a
thienopyridine drug (clopidogrel or prasugrel) or ticagrelor has become the
cornerstone in the management of coronary heart disease. (3,4) However, the
individual response to dual antiplatelet therapy is not uniform (5,6) and
consistent findings across multiple investigations support the association
between a lower degree of platelet inhibition, a high on-treatment platelet
reactivity (HPR), and the occurrence of atherothrombotic events. (7-13) These
findings have been recently extended to patients with ST-segment elevation
myocardial infarction (STEMI), who experience a high thrombotic burden and a
high rate of HPR. (14,15) Increased platelet reactivity as well as
pro-thrombotic and pro-inflammatory changes associated with myocardial
infarction have been shown to persist up to several months. (16,17) What
remains uncertain is to what extent the increased platelet activation observed
is due to the disease process itself, i.e. activation of platelets within the
abnormal coronary circulation, or to a genetic or environmental propensity for
platelets to become activated more easily in response to minimal stimuli. (18)
In the former case, one would expect that platelet status would return to
normal early after the resolution of the acute event, whereas in the latter
case platelet function may remain abnormal for a considerable time or
indefinitely. 18 More insights into these processes can result in further
optimization of medical treatment for patients with STEMI.
Recently, the new antiplatelet agent ticagrelor was introduced. The PLATO study
proved the clinical efficacy of ticagrelor and showed a decrease in
atherothrombotic events and mortality during 1 year follow-up compared to
clopidogrel.19 The ONSET/OFFSET study 20 showed using platelet function testing
in stable coronary artery disease patients that a maximal inhibiting effect on
platelet aggregation was achieved within two hours after administration of
ticagrelor. However, the onset of action in STEMI patients is unknown.
Knowledge about the onset of action of ticagrelor in the first hours after
administration will contribute to optimal treatment strategies for STEMI
patients.
Study objective
• To investigate the magnitude and time course of platelet reactivity and
platelet activation in patients with a STEMI undergoing primary percutaneous
coronary intervention (pPCI).
• To investigate the magnitude and time course of thrombin generation,
coagulation factors (X and Xa), Tissue factor pathway inhibitor (TFPI),
d-dimer-levels, and genetic variations associated with response to antiplatelet
therapy and thrombus formation in patients with a STEMI undergoing pPCI.
Study design
This is a non-randomized, open label, multicenter study, designed to
investigate the magnitude and time course of platelet activation/reactivity as
well as coagulation factors in STEMI-patients undergoing primary PCI.
Study burden and risks
Risk of participation is limited to the possibility of hematomas caused by
venapuncture.
Koekoekslaan 1
3435 CM Nieuwegein
NL
Koekoekslaan 1
3435 CM Nieuwegein
NL
Listed location countries
Age
Inclusion criteria
Patient must meet ALL of the following criteria:
• Males or females > 21 years of age and < 85 years with symptoms of acute myocardial infarction of more than 30 minutes but less than 12 hours.
• ST segment elevation of > 1 mV in 2 adjacent ECG leads, with cumulative ST- segment deviation of 6 mm or more.
• Patients should only be included if there is a reasonable expectation that PCI will be conducted within 1 hour.
Exclusion criteria
1) Patients who are unable to give informed consent or have life expectancy of < 1year
2) Subjects who have received thrombolytic therapy within 24 hours before PCI or GpIIb/IIIa-inhibitors within the last 15 days or during the PCI
3) Subjects with a contra-indication to anticoagulation or at increased bleeding risk
a. Past or present history (<1 year) of bleeding from gastrointestinal (haematemesis) melena, frank bleed in stool or visible haematuria
b. Known platelet count (<100,00/mm3 ) or coagulopathy or platelet disorder.
c. History of major recent (<30 day) surgery or trauma
4) Known Hb <6.5 mmol/L11g/dl or HCT <33%
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL33596.100.10 |