Non-ST Elevation Myocardial Infarction (NSTEMI)
Conditions
Brief summary
Immediate potent inhibition of platelet function is critical for the prevention of periprocedural ischemic event occurrences in high risk N-ST segment elevation myocardial infarction (NSTEMI) in patients undergoing percutaneous coronary intervention (PCI). Currently, dual antiplatelet therapy with aspirin and an oral P2Y12 receptor blocker (with loading doses) is widely used for PCI. However, immediate, potent and reversible inhibition of platelet aggregation is not possible even with the newer oral agents, prasugrel and ticagrelor. Therefore, an intravenously administered GPIIb/IIIa receptor inhibitor (tirofiban) or P2Y12 receptor blocker (cangrelor) with fast onset and offset of actions will provide more desired antiplatelet effects in the setting of PCI. This study will measure and compare the anti-platelet effects of Tirofiban and Cangrelor in patients presenting with N-STEMI and undergoing PCI.
Interventions
DRUGTirofiban
Patients will receive Tirofiban during the PCI procedure
DRUGCangrelor
Patients will receive Cangrelor during the PCI procedure
Sponsors
Inova Health Care Services
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. NSTEMI meeting the following criteria: 1. Patients 18 years of age or older with one or more of the following symptoms: * new ST-segment depression or transient elevation of at least 1 mm * elevations in troponin I, troponin T, or creatine kinase MB levels above ULN 2. Eligible for ticagrelor, cangrelor, aspirin, UFH, and GP IIb/IIIa inhibitor treatment. 3. Admitted at cardiac catheterization laboratory hospital or associated facility. 4. Competent mental condition to provide informed consent.
Exclusion criteria
1. Unstable angina, STEMI 2. Cardiogenic shock 3. Refractory ventricular arrhythmias 4. New York Heart Association class IV congestive heart failure 5. Cardiac arrest within 1 week of study entry 6. History of hemorrhagic or ischemic stroke, TIA, sub-arachnoid hemorrhage or intracranial neoplasm, arteriovenous malformation, or aneurysm 7. Fibrinolytic therapy within 48 hours of study entry 8. Active pathological bleeding or history of bleeding diathesis 9. Severe hepatic insufficiency 10. Current peptic ulceration 11. Increased bleeding risk, per investigator judgment 12. Known anemia (hematocrit\<25%)/thrombocytopenia (platelet count \< 100,000mm3) 13. Surgery within 4 weeks before study entry or planned surgery within 2 months after study entry 14. Any P2Y12 receptor inhibitor or GP IIb/IIIa inhibitor within 7 days of study entry 15. Receiving warfarin or other coumadin derivatives or NOACs within the last 10 days with an INR \>1.5 secs or planned use during the hospitalization period 16. Contraindication to the use of ticagrelor and/or aspirin 17. Receiving or will receive oral anticoagulation or other oral antiplatelet therapy (except aspirin) that cannot be safely discontinued within the next 3 months 18. Receiving daily NSAIDs or COX2 inhibitors that cannot be discontinued or anticipated to require \>2 weeks of daily NSAIDs or COX2 inhibitors during study 19. Investigational drug in last 30 days or presently enrolled in drug/device study 20. Women of childbearing potential (post-menopausal women can be enrolled if at least 1 year of amenorrhea or surgically sterile) 21. Condition associated with poor treatment compliance (e.g., alcoholism, mental illness, or drug dependence) 22. Inability to provide written informed consent and to understand the full meaning of the informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thrombin Receptor Activator Peptide (TRAP) Induced Platelet Aggregation (%) | 30 minutes post-start of the infusion | Assessment of platelet aggregation (%) in response to 10uM thrombin receptor activator peptide. Normal reference range is 60-100% aggregation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adenosine Diphosphate (ADP) Induced Platelet Aggregation (%) | 30 minutes post-start of the infusion | Assessment of platelet aggregation (%) in response to 20uM ADP at baseline and serially following tirofiban or cangrelor infusion. Normal reference range is 60-100% aggregation. |
| Thrombin Induced Platelet-fibrin Clot Strength (mm) | 30 minutes post-start of the infusion | Assessment of thrombin induced platelet-fibrin clot strength (mm) by thromboelastography (TEG6S). Normal reference range is 55-68 mm |
| Shear-induced Thrombus Formation (AUC) | 30 minutes after the end of the infusion. | Real time evaluation of shear-induced thrombus formation using novel RUO T-TAS plus system. AUC is calculated as time to reach 60 kPa |
Countries
United States
Participant flow
Pre-assignment details
28 participants were enrolled. 18 participants were screen failures as they did not require coronary stenting. 10 participants were assigned treatment.
Participants by arm
| Arm | Count |
|---|---|
| Tirofiban Therapy patients randomized to tirofiban therapy
Tirofiban: Patients will receive Tirofiban during the PCI procedure | 5 |
| Cangrelor Therapy patients randomized to cangrelor therapy
Cangrelor: Patients will receive Cangrelor during the PCI procedure | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Tirofiban Therapy | Cangrelor Therapy | Total |
|---|---|---|---|
| Age, Continuous | 57.0 years STANDARD_DEVIATION 12.1 | 57.3 years STANDARD_DEVIATION 12.2 | 57.3 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 5 | 1 / 5 |
| serious Total, serious adverse events | 1 / 5 | 0 / 5 |
Outcome results
Primary
Thrombin Receptor Activator Peptide (TRAP) Induced Platelet Aggregation (%)
Assessment of platelet aggregation (%) in response to 10uM thrombin receptor activator peptide. Normal reference range is 60-100% aggregation.
Time frame: 30 minutes post-start of the infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirofiban Therapy | Thrombin Receptor Activator Peptide (TRAP) Induced Platelet Aggregation (%) | 42.5 % aggregation | Standard Deviation 10.2 |
| Cangrelor Therapy | Thrombin Receptor Activator Peptide (TRAP) Induced Platelet Aggregation (%) | 71.2 % aggregation | Standard Deviation 6.9 |
Secondary
Adenosine Diphosphate (ADP) Induced Platelet Aggregation (%)
Assessment of platelet aggregation (%) in response to 20uM ADP at baseline and serially following tirofiban or cangrelor infusion. Normal reference range is 60-100% aggregation.
Time frame: 30 minutes post-start of the infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirofiban Therapy | Adenosine Diphosphate (ADP) Induced Platelet Aggregation (%) | 3.3 % aggregation | Standard Deviation 3.1 |
| Cangrelor Therapy | Adenosine Diphosphate (ADP) Induced Platelet Aggregation (%) | 39.4 % aggregation | Standard Deviation 13.1 |
Secondary
Shear-induced Thrombus Formation (AUC)
Real time evaluation of shear-induced thrombus formation using novel RUO T-TAS plus system. AUC is calculated as time to reach 60 kPa
Time frame: 30 minutes after the end of the infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirofiban Therapy | Shear-induced Thrombus Formation (AUC) | 14.1 kPa*min | Standard Deviation 13.7 |
| Cangrelor Therapy | Shear-induced Thrombus Formation (AUC) | 1004 kPa*min | Standard Deviation 884 |
Secondary
Thrombin Induced Platelet-fibrin Clot Strength (mm)
Assessment of thrombin induced platelet-fibrin clot strength (mm) by thromboelastography (TEG6S). Normal reference range is 55-68 mm
Time frame: 30 minutes post-start of the infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirofiban Therapy | Thrombin Induced Platelet-fibrin Clot Strength (mm) | 63.9 mm | Standard Deviation 2.7 |
| Cangrelor Therapy | Thrombin Induced Platelet-fibrin Clot Strength (mm) | 62.3 mm | Standard Deviation 3.6 |