Crushed Ticagrelor Versus Eptifibatide Bolus + Clopidogrel

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effects of Crushed Ticagrelor Versus Eptifibatide Bolus +Clopidogrel in Troponin-Negative ACS Patients Undergoing Coronary Intervention

Conditions
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Acute Coronary Syndrome, Angina, Unstable

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Eptifibatide
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unstable angina/troponin negative ACS. Exclusion Criteria: need for oral anticoagulation therapy (Warfarin, Dabigatran, Rivaroxaban, Apixaban, Edoxaban) 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) surgery<4 weeks use of any thienopyridines (Clopidogrel, Prasugrel) 7 days prior to randomization administration of GP IIb/IIIa inhibitors bleeding diathesis or major bleeding episode within 2 weeks thrombocytopenia (Platelet count < 100000) incessant chest pain 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 anemia with HCT<30%.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ticagrelor<br>crushed ticagrelor (180 mg); (n=50 patients) | Drug: Ticagrelor<br>* 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.<br>* Other names: Brilinta;|
| Active Comparator: Eptifibatide bolus+clopidogrel<br>Eptifibatide bolus (180 mcg/kg x 2 boluses) + clopidogrel 600 mg and heparin low-dose (n=50 patients) | Drug: Eptifibatide<br>* 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.<br>* Other names: Integrilin;Drug: Clopidogrel<br> <br> * Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 times (at baseline, and at 0.5, 2, 4, and 24 hours after loading dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At baseline and every 8 hours post- PCI | 
| 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 | At baseline and at 0.5, 2, 4, and 24 hours after loading dose | 
| Change in Hemoglobin Levels (g/dL) | Hemoglobin levels (g/dL) will be measured at baseline and on the next day after PCI. | At baseline and at 24 hours post-PCI | 
| A Change in Hematocrit Levels | Hematocrit levels (%) will be measured at baseline and on the next day after PCI. | At baseline and at 24 hours post-PCI | 
| 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. | 24 hours after the PCI | 
| Activated Clotting Time (ACT), Seconds | The Level of the highest ACT during PCI will be compared between the groups | At the end of PCI | 
| 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. | At 24 hours post-PCI | 
| 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. | At 1 year post-PCI | 
| 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. | At 24 hours post-PCI | 
| 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. | At 1 year post-PCI | 
| Number of Patients With Negative Clinical Outcomes | The rates of death, myocardial infarction, and revascularization at 1-year post-PCI. | At 1-year post-PCI |