STEMI - ST Elevation Myocardial Infarction
Conditions
Brief summary
This study evaluates differences in the extent of myocardial necrosis noted by cardiac MRI in patients with ST-elevation myocardial infarction randomized to receive cangrelor during their percutaneous coronary intervention and compares them to patients randomized to not receive cangrelor.
Detailed description
Cangrelor is a direct-acting and reversible intravenously administered platelet inhibitor approved as an adjunct to percutaneous intervention (PCI) for reducing the risk of periprocedural myocardial infarction, repeat coronary revascularization, and stent thrombosis. As it has a quick onset of action (2 minutes) compared to traditional oral platelet inhibitors, cangrelor is emerging as an important new option for use in patients undergoing percutaneous intervention who have not been treated with oral platelet inhibitors. Furthermore, multiple studies have demonstrated that patients with ST-elevation myocardial infarction (STEMI) who undergo emergent PCI do not have optimal platelet inhibition even after administration of a loading dose of traditional oral platelet inhibitors. However, the clinical significance of complete platelet inhibition around the time of PCI is not fully understood. The primary objective is to characterize the utility of immediate platelet inhibition with intravenous cangrelor in patients presenting with an acute STEMI by assessing the extent of infarct size (either enzymatically or by imaging). If the findings are favorable, this may suggest that immediate platelet inhibition is an important part of care in this patient population.
Interventions
DRUGCangrelor
Cangrelor 30 mcg/kg bolus followed by a 4 mcg/kg/min intravenous infusion prior to PCI will be given. It will be continued for ≥ 2 hours or for the duration of the procedure, whichever is longer.
Sponsors
Khaled Ziada, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patients with an acute STEMI with the University of Kentucky as the institution of presentation with plans for PCI * English-speaking
Exclusion criteria
* Pregnant patients * Prisoners * Patients who are unable to provide his/her own consent * Patients with a prior history of myocardial infarction * Patients who have received thrombolytics * Patients on systemic anticoagulation * Patients who are hemodynamically unstable with evidence of shock * Patients who are mechanically intubated * Patients with devices not MRI compatible * Patients with chronic kidney disease, glomerular filtration rate less than 30 * Patients who are already on dual antiplatelet therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Myocardial Infarction Size | 48 hours and 3 months | Cardiac MRI is obtained at 48 hours and 3 months to compare differences in infarct size. The outcome is assessed as the difference in infarct size between 48 hours and 3 months in each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Reactivity | 10 minutes | Platelet reactivity testing will be performed 10 minutes after infusion has started. |
| Peripheral Blood Count Quantification | 6 hours | Flow cytometry on peripheral blood will be performed to quantify peripheral counts of inflammatory cells, stem cells, and monocyte subtypes. |
| Interferon (IFN)-α2 | 6 hours | ELISA assay will be performed on plasma to quantify the amount of the inflammatory cytokine interleukin-6 in pg/mL. |
| IFN-γ | 6 hours | ELISA assay. |
| Macrophage-derived Chemokine | 6 hours | ELISA assay macrophage-derived chemokine |
Countries
United States
Participant flow
Recruitment details
Patients were recruited in the cardiac catheterization laboratory.
Pre-assignment details
Patients were randomized upon recruitment to the standard of care alone or standard of care in addition to cangrelor
Participants by arm
| Arm | Count |
|---|---|
| Cangrelor The final subject count in this arm is 13. | 13 |
| No Cangrelor The final subject number in this arm is 9. | 9 |
| Total | 22 |
Baseline characteristics
| Characteristic | Total | No Cangrelor | Cangrelor |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 9.2 | 57.4 years STANDARD_DEVIATION 7.7 | 58.9 years STANDARD_DEVIATION 10.7 |
| BMI | 29.96 kg/m2 STANDARD_DEVIATION 7.24 | 31.6 kg/m2 STANDARD_DEVIATION 8.1 | 28.8 kg/m2 STANDARD_DEVIATION 2 |
| Diabetes | 7 Participants | 4 Participants | 3 Participants |
| Hyperlipidemia | 7 Participants | 4 Participants | 3 Participants |
| Hypertension | 14 Participants | 6 Participants | 8 Participants |
| No prior platelet therapy | 19 Participants | 8 Participants | 11 Participants |
| Peripehral vascular disease | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 19 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 16 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 9 |
| other Total, other adverse events | 0 / 13 | 0 / 9 |
| serious Total, serious adverse events | 0 / 13 | 0 / 9 |
Outcome results
Primary
Change in Myocardial Infarction Size
Cardiac MRI is obtained at 48 hours and 3 months to compare differences in infarct size. The outcome is assessed as the difference in infarct size between 48 hours and 3 months in each group.
Time frame: 48 hours and 3 months
Population: standard of care alone vs. Standard of care in addition to cangrelor
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cangrelor | Change in Myocardial Infarction Size | 48 hours | 8.6 percent of left ventricular mass | Standard Error 1.6 |
| Cangrelor | Change in Myocardial Infarction Size | 3 months | 6.7 percent of left ventricular mass | Standard Error 1.5 |
| No Cangrelor | Change in Myocardial Infarction Size | 48 hours | 11.1 percent of left ventricular mass | Standard Error 2.1 |
| No Cangrelor | Change in Myocardial Infarction Size | 3 months | 6.98 percent of left ventricular mass | Standard Error 2.1 |
Secondary
IFN-γ
ELISA assay.
Time frame: 6 hours
Population: Plasma levels
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cangrelor | IFN-γ | 41.4 pg/mL | Standard Error 8.5 |
| No Cangrelor | IFN-γ | 103.3 pg/mL | Standard Error 19.6 |
Secondary
Interferon (IFN)-α2
ELISA assay will be performed on plasma to quantify the amount of the inflammatory cytokine interleukin-6 in pg/mL.
Time frame: 6 hours
Population: Plasma level
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cangrelor | Interferon (IFN)-α2 | 33.2 pg/mL | Standard Error 5.9 |
| No Cangrelor | Interferon (IFN)-α2 | 57.8 pg/mL | Standard Error 4.6 |
Secondary
Macrophage-derived Chemokine
ELISA assay macrophage-derived chemokine
Time frame: 6 hours
Population: plasma levels
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cangrelor | Macrophage-derived Chemokine | 593.3 pg/mL | Standard Error 44 |
| No Cangrelor | Macrophage-derived Chemokine | 873.8 pg/mL | Standard Error 63.8 |
Secondary
Peripheral Blood Count Quantification
Flow cytometry on peripheral blood will be performed to quantify peripheral counts of inflammatory cells, stem cells, and monocyte subtypes.
Time frame: 6 hours
Population: standard of care alone vs. Standard of care in addition to cangrelor
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cangrelor | Peripheral Blood Count Quantification | granulocyte platelet aggregates | 1166.7 cells per microliter | Standard Error 190.7 |
| Cangrelor | Peripheral Blood Count Quantification | Monocyte-platelet aggregate | 139.8 cells per microliter | Standard Error 31.1 |
| No Cangrelor | Peripheral Blood Count Quantification | granulocyte platelet aggregates | 2550.4 cells per microliter | Standard Error 533.7 |
| No Cangrelor | Peripheral Blood Count Quantification | Monocyte-platelet aggregate | 333.9 cells per microliter | Standard Error 44.9 |
Secondary
Platelet Reactivity
Platelet reactivity testing will be performed 10 minutes after infusion has started.
Time frame: 10 minutes
Population: standard of care alone vs. Standard of care in addition to cangrelor
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cangrelor | Platelet Reactivity | ADP-induced aggregation | 102.2 seconds | Standard Error 24.88 |
| Cangrelor | Platelet Reactivity | TRAP-induced aggregation | 285.8 seconds | Standard Error 86.1 |
| No Cangrelor | Platelet Reactivity | ADP-induced aggregation | 333.4 seconds | Standard Error 63.3 |
| No Cangrelor | Platelet Reactivity | TRAP-induced aggregation | 624.8 seconds | Standard Error 106 |