Ticagrelor and Eptifibatide Bolus-Only Versus Ticagrelor and Eptifibatide Bolus Plus Abbreviated Infusion

Phase 2

Completed

Brief Summary: This purpose of this study is to measure platelet response to ticagrelor and eptifibatide bolus-only compared with ticagrelor and eptifibatide bolus plus 2-hour infusion administrated after cardiac catheterization in patients undergoing non-emergent percutaneous coronary intervention.

Detailed Description: In this study, 70 patients with Acute Coronary Syndrome who are undergoing non-emergent percutaneous coronary intervention (PCI) will be randomized to ticagrelor loading dose and eptifibatide bolus-only versus ticagrelor loading dose and eptifibatide bolus plus 2 hour infusion administrated after cardiac catheterization, but before PCI. Platelet function testing will be performed at baseline and follow-up.

Recruitment & Eligibility

Inclusion Criteria

For inclusion in the study subjects should fulfill the following criteria:

Provision of informed consent prior to any study specific procedures
Males and females aged 19 years and older
Congruent to the PLATO trial, at least two of the following three criteria have to be met:
ST-segment changes on electrocardiography, indicating ischemia; (In electrocardiography, the ST segment connects the QRS complex and the T wave and has a duration of 0.080 to 0.120 sec (80 to 120 ms).
a positive test of a biomarker, indicating myocardial necrosis; or one of several risk factors;
age >60 years
previous myocardial infarction or Coronary-Artery Bypass Grafting [CABG];
coronary artery disease with stenosis of ≥50% in at least two vessels;
previous ischemic stroke, transient ischemic attack, carotid stenosis of at least 50%, or cerebral revascularization;
diabetes mellitus;
peripheral arterial disease;
or chronic renal dysfunction, defined as a creatinine clearance of <60 ml per minute per 1.73 m2 of body surface area).
patients with symptoms of unstable angina lasting ≥10 min and either an elevated troponin I level or newly developed ST-segment depression of 1 mm or transient ST-segment elevation of 1 mm will also be included.

Exclusion Criteria

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

Patients with active pathological bleeding or a history of intracranial bleeding;
patients with planned to urgent coronary artery bypass graft surgery;
severe hepatic impairment;
concomitant therapy with a strong cytochrome P-450 3A inhibitors, where 3A is s subfamily of the cytochrome P450 superfamily of genes;
surgery<4 weeks;
the use of any thienopyridine (within the previous two weeks);
upstream use of Glycoprotein (GP) IIb/IIIa inhibitors;
bleeding diathesis or major bleeding episode within 2 weeks;
a need for oral anticoagulation therapy;
thrombocytopenia;
presence of thrombus in the coronary artery; incessant chest pain or hemodynamic instability;
and patients with glomerular filtration rate (GFR)<30 mL/min or on hemodialysis.
maintenance dose of aspirin above 100mg
history of allergies to Ticagrelor
patients at increased risk of bradycardic events (e.g., patients who have sick sinus syndrome, 2nd or 3rd degree Atrioventricular block (AV block), or bradycardic related syncope and not protected with a pacemaker
women who are pregnant or breastfeeding

Arm && Interventions

Group	Intervention	Description
Ticagrelor and Eptifibatide bolus	Ticagrelor	Ticagrelor 180 mg i.v. Eptifibatide (2 boluses 180µg/Kg each 10 min apart)
Ticagrelor & Eptifibatide bolus+infusion	Eptifibatide	Ticagrelor 180 mg i.v. Eptifibatide (2 boluses 180µg/Kg, 10 min apart, followed by 2µg/Kg/min infusion for 2 hours)
Ticagrelor and Eptifibatide bolus	Eptifibatide	Ticagrelor 180 mg i.v. Eptifibatide (2 boluses 180µg/Kg each 10 min apart)
Ticagrelor & Eptifibatide bolus+infusion	Ticagrelor	Ticagrelor 180 mg i.v. Eptifibatide (2 boluses 180µg/Kg, 10 min apart, followed by 2µg/Kg/min infusion for 2 hours)

Primary Outcome Measures

Name	Time	Method
Change in Percent Inhibition of Platelet Aggregation (%IPA)	Baseline and 2 hours	Change from baseline in %IPA at 2 hours after stimulation with 20µM ADP (µM-micromolar, ADP-Adenosine diphosphate), measured in blood by an aggregometer among patients randomized to ticagrelor and 2 boluses of eptifibatide vs. ticagrelor and 2 boluses plus infusion of eptifibatide.

Secondary Outcome Measures

Name	Time	Method
Bleeding Complications	up to 24 hours	Number of subjects that developed gastrointestinal bleeding after Percutaneous Coronary Intervention (PCI). These subjects were categorized under Bleeding Academic Research Consortium 3b. Type 3b bleeding includes overt bleeding plus a hemoglobin drop of ≥5 g/dL (provided the hemoglobin drop is related to bleeding), cardiac tamponade, bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid), and bleeding requiring intravenous vasoactive drugs.
Periprocedural Myocardial Infarction (PMI)	Up to 24 hours	Number of subjects that developed PMI. Periprocedural myocardial infarction (PMI) was defined as an increase in troponin I values \>5 x 99th percentile the upper limit of normal in patients with normal baseline value on admission, or a rise of troponin I values \>20% after PCI if the baseline value was elevated.
High On-treatment Platelet Reactivity (HPR)	Comparing baseline and follow-up (2 hours)	Percentage of participants with HPR. HPR is defined as platelet aggregation \>59% in response to 20 µM ADP.