Acute Coronary Syndrome, Angina, Unstable
Conditions
Brief summary
Patients with troponin-negative acute coronary syndrome (ACS) are not routinely pre-treated with P2Y12 inhibitors and the rate of high on-treatment platelet reactivity (HPR) remains elevated after a loading dose of ticagrelor at the time of percutaneous coronary intervention (PCI). This suggests that faster platelet inhibition with crushed ticagrelor , eptifibatide , or cangrelor is needed to reduce HPR and periprocedural myocardial infarction and injury (PMI). The present study compared the effects of crushed ticagrelor vs. eptifibatide bolus + clopidogrel in troponin-negative ACS patients undergoing PCI.
Detailed description
Platelet activation and accumulation causes the formation of blood clots that may cause heart attack. As a standard of care, the doctor can prescribe medications such as are ticagrelor, eptifibatide, clopidogrel, to prevent the formation of blood clots. 100 patients with unstable angina, both male and female, will be randomized to either Group A- Crushed Ticagrelor or Group B- Eptifibatide bolus +Clopidogrel administrated immediately before PCI. Platelet function testing, troponin, and ECG will be performed.
Interventions
DRUGTicagrelor
After randomization, a blood sample will be obtained at baseline for platelet function study, the study drugs, crushed ticagrelor will be administered. Patients will undergo PCI using drug-eluting stents or bare-metal stents. Blood samples will be obtained at 30 mins, 2, 4, and 24 h after PCI for platelet function tests.
DRUGEptifibatide
After randomization, a blood sample will be obtained at baseline for platelet function test, the study drugs, clopidogrel and eptifibatide bolus will be administered. Patients will undergo PCI using drug-eluting stents or bare-metal stents. Blood samples will be obtained at 30 mins, 2, 4, and 24 h after PCI for platelet function tests.
DRUGClopidogrel
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with unstable angina/troponin negative ACS.
Exclusion criteria
1. need for oral anticoagulation therapy (Warfarin, Dabigatran, Rivaroxaban, Apixaban, Edoxaban) 2. increased risk of bradycardia, and the associated therapy with a strong cytochrome P-450 inhibitors (anti-retroviral agents, antifungal agents and some antibiotics eg. Indinavir, Nelfinavir, Lopinavir, Ritonavir, Itraconazole, Ketoconazole, Voriconazole, Clarithromycin, Telithormycin) 3. surgery\<4 weeks 4. use of any thienopyridines (Clopidogrel, Prasugrel) 7 days prior to randomization 5. administration of GP IIb/IIIa inhibitors 6. bleeding diathesis or major bleeding episode within 2 weeks 7. thrombocytopenia (Platelet count \< 100000) 8. incessant chest pain 9. hemodynamic instability (Mean arterial pressure \< 65 mm Hg; need for vasopressor or inotropic agents; need for mechanical circulatory support for coronary intervention), NSTEMI as evidenced by elevation of troponin levels (Troponin \> 0.034 ng/ml); renal failure with a serum creatinine \>2.0 mg/dL 10. anemia with HCT\<30%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 5 times (at baseline, and at 0.5, 2, 4, and 24 hours after loading dose) | We assessed platelet aggregation at baseline and during PCI by light transmission aggregomerty. The primary efficacy measure was HPR defined as platelet aggregation \>59% at 2 h measured by the Chronlog aggregometer after stimulation with ADP 20 µM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Aggregation Levels | At baseline and at 0.5, 2, 4, and 24 hours after loading dose | The rates of platelet aggregation with ADP and TRAP will be measured in patients randomized to crushed ticagrelor vs. eptifibatide bolus+clopidogrel |
| Change in Hemoglobin Levels (g/dL) | At baseline and at 24 hours post-PCI | Hemoglobin levels (g/dL) will be measured at baseline and on the next day after PCI. |
| A Change in Hematocrit Levels | At baseline and at 24 hours post-PCI | Hematocrit levels (%) will be measured at baseline and on the next day after PCI. |
| Heparin Dose, Unit/Kg | 24 hours after the PCI | For the heparin dose range for the two groups would have a minimum dose of 4693 and a maximum dose of 11141 units per kilogram.The higher the number is indicative that a higher dose of heparin is needed based on kilogram weight. |
| Number of Participants With a Periprocedural Myocardial Infarction and Injury (PMI) | At baseline and every 8 hours post- PCI | The rate of PMI will be compared in patients randomized to crushed ticagrelor vs. eptifibatide bolus +clopidogrel |
| Number of Patients With Minor Bleeding Complications | At 24 hours post-PCI | We evaluated the number of patients with minor bleeding complications. Minor bleeding, based on Bleeding Academic Research Consortium (BARC), was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to \<5 g/dL. |
| Number of Patients With Major Bleeding Complications | At 24 hours post-PCI | We evaluated the number of patients with major bleeding complications. Major bleeding, based on Bleeding Academic Research Consortium (BARC), was defined as type 3a, bleeding + hemoglobin drop of 3 to \<5 g/dL; type 3b, bleeding + hemoglobin drop ≥5 g/dL; and type C, intracranial hemorrhage. |
| Number of Patients With Negative Clinical Outcomes | At 1-year post-PCI | The rates of death, myocardial infarction, and revascularization at 1-year post-PCI. |
| Activated Clotting Time (ACT), Seconds | At the end of PCI | The Level of the highest ACT during PCI will be compared between the groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor crushed ticagrelor (180 mg); (n=50 patients)
Ticagrelor: After randomization, a blood sample will be obtained at baseline for platelet function study, the study drugs, crushed ticagrelor will be administered. Patients will undergo PCI using drug-eluting stents or bare-metal stents. Blood samples will be obtained at 30 mins, 2, 4, and 24 h after PCI for platelet function tests. | 50 |
| Eptifibatide Bolus+Clopidogrel Eptifibatide bolus (180 mcg/kg x 2 boluses) + clopidogrel 600 mg and heparin low-dose (n=50 patients)
Eptifibatide: After randomization, a blood sample will be obtained at baseline for platelet function test, the study drugs, clopidogrel and eptifibatide bolus will be administered. Patients will undergo PCI using drug-eluting stents or bare-metal stents. Blood samples will be obtained at 30 mins, 2, 4, and 24 h after PCI for platelet function tests.
Clopidogrel | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | blood samples hemolyzed | 0 | 2 |
Baseline characteristics
| Characteristic | Eptifibatide Bolus+Clopidogrel | Total | Ticagrelor |
|---|---|---|---|
| Age, Customized >=19 years | 50 participants | 100 participants | 50 participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 50 participants | 100 participants | 50 participants |
| Sex: Female, Male Female | 12 Participants | 31 Participants | 19 Participants |
| Sex: Female, Male Male | 38 Participants | 69 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 50 | 0 / 50 |
| other Total, other adverse events | 0 / 50 | 0 / 50 |
| serious Total, serious adverse events | 1 / 50 | 0 / 50 |
Outcome results
Primary
Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR)
We assessed platelet aggregation at baseline and during PCI by light transmission aggregomerty. The primary efficacy measure was HPR defined as platelet aggregation \>59% at 2 h measured by the Chronlog aggregometer after stimulation with ADP 20 µM.
Time frame: 5 times (at baseline, and at 0.5, 2, 4, and 24 hours after loading dose)
Population: 2 participants of the Eptifibatide Bolus+Clopidogrel arm were unable to be analyzed due to blood samples being hemolyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ticagrelor | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 0.5 h (n-50, n-48) | 24 count of participants |
| Ticagrelor | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 4 h (n-50, n-48) | 0 count of participants |
| Ticagrelor | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 2 h (n-50, n-48) | 6 count of participants |
| Ticagrelor | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 24 h (n-50, n-48) | 2 count of participants |
| Ticagrelor | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | Baseline (n-50, n-48) | 37 count of participants |
| Eptifibatide Bolus+Clopidogrel | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 24 h (n-50, n-48) | 5 count of participants |
| Eptifibatide Bolus+Clopidogrel | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | Baseline (n-50, n-48) | 33 count of participants |
| Eptifibatide Bolus+Clopidogrel | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 0.5 h (n-50, n-48) | 0 count of participants |
| Eptifibatide Bolus+Clopidogrel | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 2 h (n-50, n-48) | 0 count of participants |
| Eptifibatide Bolus+Clopidogrel | Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR) | 4 h (n-50, n-48) | 0 count of participants |
Secondary
A Change in Hematocrit Levels
Hematocrit levels (%) will be measured at baseline and on the next day after PCI.
Time frame: At baseline and at 24 hours post-PCI
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor | A Change in Hematocrit Levels | Baseline (hematocrit, %) | 40.11 hematocrit (%) | Standard Deviation 5.36 |
| Ticagrelor | A Change in Hematocrit Levels | Post-PCI (hematocrit, %) | 37.68 hematocrit (%) | Standard Deviation 4.85 |
| Eptifibatide Bolus+Clopidogrel | A Change in Hematocrit Levels | Baseline (hematocrit, %) | 40.02 hematocrit (%) | Standard Deviation 4.49 |
| Eptifibatide Bolus+Clopidogrel | A Change in Hematocrit Levels | Post-PCI (hematocrit, %) | 37.5 hematocrit (%) | Standard Deviation 4.2 |
Secondary
Activated Clotting Time (ACT), Seconds
The Level of the highest ACT during PCI will be compared between the groups
Time frame: At the end of PCI
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | Activated Clotting Time (ACT), Seconds | 332 s | Standard Deviation 48 |
| Eptifibatide Bolus+Clopidogrel | Activated Clotting Time (ACT), Seconds | 278 s | Standard Deviation 47 |
Secondary
Change in Hemoglobin Levels (g/dL)
Hemoglobin levels (g/dL) will be measured at baseline and on the next day after PCI.
Time frame: At baseline and at 24 hours post-PCI
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor | Change in Hemoglobin Levels (g/dL) | Baseline (hemoglobin, g/dL) | 13.52 g/dL | Standard Deviation 2 |
| Ticagrelor | Change in Hemoglobin Levels (g/dL) | Post-PCI (hemoglobin, g/dL) | 12.73 g/dL | Standard Deviation 1.81 |
| Eptifibatide Bolus+Clopidogrel | Change in Hemoglobin Levels (g/dL) | Baseline (hemoglobin, g/dL) | 13.34 g/dL | Standard Deviation 1.62 |
| Eptifibatide Bolus+Clopidogrel | Change in Hemoglobin Levels (g/dL) | Post-PCI (hemoglobin, g/dL) | 12.71 g/dL | Standard Deviation 1.6 |
Secondary
Heparin Dose, Unit/Kg
For the heparin dose range for the two groups would have a minimum dose of 4693 and a maximum dose of 11141 units per kilogram.The higher the number is indicative that a higher dose of heparin is needed based on kilogram weight.
Time frame: 24 hours after the PCI
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | Heparin Dose, Unit/Kg | 8854 units per kilogram | Standard Deviation 2287 |
| Eptifibatide Bolus+Clopidogrel | Heparin Dose, Unit/Kg | 6021 units per kilogram | Standard Deviation 1328 |
Secondary
Number of Participants With a Periprocedural Myocardial Infarction and Injury (PMI)
The rate of PMI will be compared in patients randomized to crushed ticagrelor vs. eptifibatide bolus +clopidogrel
Time frame: At baseline and every 8 hours post- PCI
Population: 2 participants of the Eptifibatide Bolus+Clopidogrel arm were unable to be analyzed due to blood samples being hemolyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Number of Participants With a Periprocedural Myocardial Infarction and Injury (PMI) | 24 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Participants With a Periprocedural Myocardial Infarction and Injury (PMI) | 14 Participants |
Secondary
Number of Patients With Major Bleeding Complications
We evaluated the number of patients with major bleeding complications. Major bleeding, based on Bleeding Academic Research Consortium (BARC), was defined as type 3a, bleeding + hemoglobin drop of 3 to \<5 g/dL; type 3b, bleeding + hemoglobin drop ≥5 g/dL; and type C, intracranial hemorrhage.
Time frame: At 1 year post-PCI
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Number of Patients With Major Bleeding Complications | 0 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Major Bleeding Complications | 0 Participants |
Secondary
Number of Patients With Major Bleeding Complications
We evaluated the number of patients with major bleeding complications. Major bleeding, based on Bleeding Academic Research Consortium (BARC), was defined as type 3a, bleeding + hemoglobin drop of 3 to \<5 g/dL; type 3b, bleeding + hemoglobin drop ≥5 g/dL; and type C, intracranial hemorrhage.
Time frame: At 24 hours post-PCI
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Number of Patients With Major Bleeding Complications | 0 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Major Bleeding Complications | 0 Participants |
Secondary
Number of Patients With Minor Bleeding Complications
We evaluated the number of patients with minor bleeding complications. Minor bleeding, based on Bleeding Academic Research Consortium (BARC), was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to \<5 g/dL.
Time frame: At 24 hours post-PCI
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Number of Patients With Minor Bleeding Complications | 0 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Minor Bleeding Complications | 0 Participants |
Secondary
Number of Patients With Minor Bleeding Complications
We evaluated the number of patients with minor bleeding complications. Minor bleeding, based on Bleeding Academic Research Consortium (BARC), was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to \<5 g/dL.
Time frame: At 1 year post-PCI
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ticagrelor | Number of Patients With Minor Bleeding Complications | 0 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Minor Bleeding Complications | 0 Participants |
Secondary
Number of Patients With Negative Clinical Outcomes
The rates of death, myocardial infarction, and revascularization at 1-year post-PCI.
Time frame: At 1-year post-PCI
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ticagrelor | Number of Patients With Negative Clinical Outcomes | Death | 2 Participants |
| Ticagrelor | Number of Patients With Negative Clinical Outcomes | Myocardial infarction | 0 Participants |
| Ticagrelor | Number of Patients With Negative Clinical Outcomes | Revascularization | 1 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Negative Clinical Outcomes | Death | 0 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Negative Clinical Outcomes | Myocardial infarction | 0 Participants |
| Eptifibatide Bolus+Clopidogrel | Number of Patients With Negative Clinical Outcomes | Revascularization | 0 Participants |
Secondary
Platelet Aggregation Levels
The rates of platelet aggregation with ADP and TRAP will be measured in patients randomized to crushed ticagrelor vs. eptifibatide bolus+clopidogrel
Time frame: At baseline and at 0.5, 2, 4, and 24 hours after loading dose
Population: We did not have enough plasma sample to measure TRAP 10 at 4, 24 h.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ticagrelor | Platelet Aggregation Levels | 2 h (TRAP 20) | 51 μmol/L | Standard Deviation 8 |
| Ticagrelor | Platelet Aggregation Levels | 4 h (TRAP 20) | 48 μmol/L | Standard Deviation 12 |
| Ticagrelor | Platelet Aggregation Levels | Baseline (ADP 20) | 65 μmol/L | Standard Deviation 14 |
| Ticagrelor | Platelet Aggregation Levels | 0.5 h (ADP 20) | 53 μmol/L | Standard Deviation 12 |
| Ticagrelor | Platelet Aggregation Levels | 2 h (ADP 20) | 35 μmol/L | Standard Deviation 11 |
| Ticagrelor | Platelet Aggregation Levels | 4 h (ADP 20) | 23 μmol/L | Standard Deviation 9 |
| Ticagrelor | Platelet Aggregation Levels | 24 h (ADP 20) | 25 μmol/L | Standard Deviation 10 |
| Ticagrelor | Platelet Aggregation Levels | Baseline (ADP 5) | 56 μmol/L | Standard Deviation 12 |
| Ticagrelor | Platelet Aggregation Levels | 0.5 h (ADP 5) | 44 μmol/L | Standard Deviation 17 |
| Ticagrelor | Platelet Aggregation Levels | 2 h (ADP 5) | 24 μmol/L | Standard Deviation 13 |
| Ticagrelor | Platelet Aggregation Levels | 4 h (ADP 5) | 15 μmol/L | Standard Deviation 9 |
| Ticagrelor | Platelet Aggregation Levels | 24 h (ADP 5) | 18 μmol/L | Standard Deviation 14 |
| Ticagrelor | Platelet Aggregation Levels | Baseline (TRAP 20) | 68 μmol/L | Standard Deviation 14 |
| Ticagrelor | Platelet Aggregation Levels | 0.5 h (TRAP 20) | 60 μmol/L | Standard Deviation 13 |
| Ticagrelor | Platelet Aggregation Levels | 24 h (TRAP 20) | 54 μmol/L | Standard Deviation 11 |
| Ticagrelor | Platelet Aggregation Levels | Baseline (TRAP 10) | 56 μmol/L | Standard Deviation 18 |
| Ticagrelor | Platelet Aggregation Levels | 0.5 h (TRAP 10) | 48 μmol/L | Standard Deviation 19 |
| Ticagrelor | Platelet Aggregation Levels | 2 h (TRAP 10) | 37 μmol/L | Standard Deviation 17 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 4 h (TRAP 20) | 14 μmol/L | Standard Deviation 10 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 2 h (TRAP 20) | 6 μmol/L | Standard Deviation 5 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 2 h (ADP 5) | .3 μmol/L | Standard Deviation 0.93 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 0.5 h (TRAP 20) | 3.9 μmol/L | Standard Deviation 3.6 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 2 h (TRAP 10) | 1.57 μmol/L | Standard Deviation 2 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | Baseline (ADP 20) | 62 μmol/L | Standard Deviation 10 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 4 h (ADP 5) | 1.6 μmol/L | Standard Deviation 1.5 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 0.5 h (ADP 20) | 1.3 μmol/L | Standard Deviation 2 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 24 h (TRAP 20) | 51 μmol/L | Standard Deviation 11 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 2 h (ADP 20) | .34 μmol/L | Standard Deviation 1 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 24 h (ADP 5) | 27 μmol/L | Standard Deviation 17 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 4 h (ADP 20) | 3.5 μmol/L | Standard Deviation 2 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 0.5 h (TRAP 10) | 1.18 μmol/L | Standard Deviation 1 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 24 h (ADP 20) | 38 μmol/L | Standard Deviation 9 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | Baseline (TRAP 20) | 67 μmol/L | Standard Deviation 16 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | Baseline (ADP 5) | 54 μmol/L | Standard Deviation 13 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | Baseline (TRAP 10) | 54 μmol/L | Standard Deviation 19 |
| Eptifibatide Bolus+Clopidogrel | Platelet Aggregation Levels | 0.5 h (ADP 5) | 1.18 μmol/L | Standard Deviation 4 |