Crushed Ticagrelor Versus Eptifibatide Bolus + Clopidogrel

Phase 2

Completed

Conditions: Angina, Unstable
Acute Coronary Syndrome

Interventions: Drug: Ticagrelor
Drug: Eptifibatide
Drug: Clopidogrel

Registration Number: NCT02925923

Lead Sponsor: University of Alabama at Birmingham

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

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%.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eptifibatide bolus+clopidogrel	Clopidogrel	Eptifibatide bolus (180 mcg/kg x 2 boluses) + clopidogrel 600 mg and heparin low-dose (n=50 patients)
Ticagrelor	Ticagrelor	crushed ticagrelor (180 mg); (n=50 patients)
Eptifibatide bolus+clopidogrel	Eptifibatide	Eptifibatide bolus (180 mcg/kg x 2 boluses) + clopidogrel 600 mg and heparin low-dose (n=50 patients)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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.
Activated Clotting Time (ACT), Seconds	At the end of PCI	The Level of the highest ACT during PCI will be compared between the groups
Number of Patients With Minor Bleeding Complications	At 1 year 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 1 year 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.