Crushed Ticagrelor Versus Eptifibatide Bolus + Clopidogrel
Primary Purpose
Acute Coronary Syndrome, Angina, Unstable
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ticagrelor
Eptifibatide
Clopidogrel
Sponsored by
About this trial
This is an interventional treatment trial for Acute Coronary Syndrome
Eligibility Criteria
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%.
Sites / Locations
- University of Alabama
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Ticagrelor
Eptifibatide bolus+clopidogrel
Arm Description
crushed ticagrelor (180 mg); (n=50 patients)
Eptifibatide bolus (180 mcg/kg x 2 boluses) + clopidogrel 600 mg and heparin low-dose (n=50 patients)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
Change in Hemoglobin Levels (g/dL)
Hemoglobin levels (g/dL) will be measured at baseline and on the next day after PCI.
A Change in Hematocrit Levels
Hematocrit levels (%) will be measured at baseline and on the next day after 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.
Activated Clotting Time (ACT), Seconds
The Level of the highest ACT during PCI will be compared between the groups
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.
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.
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.
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.
Number of Patients With Negative Clinical Outcomes
The rates of death, myocardial infarction, and revascularization at 1-year post-PCI.
Full Information
NCT ID
NCT02925923
First Posted
September 27, 2016
Last Updated
April 22, 2020
Sponsor
University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT02925923
Brief Title
Crushed Ticagrelor Versus Eptifibatide Bolus + Clopidogrel
Official Title
The Effects of Crushed Ticagrelor Versus Eptifibatide Bolus +Clopidogrel in Troponin-Negative ACS Patients Undergoing Coronary Intervention
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
November 1, 2016 (Actual)
Primary Completion Date
January 30, 2018 (Actual)
Study Completion Date
December 1, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome, Angina, Unstable
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ticagrelor
Arm Type
Active Comparator
Arm Description
crushed ticagrelor (180 mg); (n=50 patients)
Arm Title
Eptifibatide bolus+clopidogrel
Arm Type
Active Comparator
Arm Description
Eptifibatide bolus (180 mcg/kg x 2 boluses) + clopidogrel 600 mg and heparin low-dose (n=50 patients)
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Other Intervention Name(s)
Brilinta
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Eptifibatide
Other Intervention Name(s)
Integrilin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Primary Outcome Measure Information:
Title
Number of Participants With a Change in high-on Treatment Platelet Reactivity (HPR)
Description
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)
Secondary Outcome Measure Information:
Title
Number of Participants With a Periprocedural Myocardial Infarction and Injury (PMI)
Description
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
Title
Platelet Aggregation Levels
Description
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
Title
Change in Hemoglobin Levels (g/dL)
Description
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
Title
A Change in Hematocrit Levels
Description
Hematocrit levels (%) will be measured at baseline and on the next day after PCI.
Time Frame
At baseline and at 24 hours post-PCI
Title
Heparin Dose, Unit/Kg
Description
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
Title
Activated Clotting Time (ACT), Seconds
Description
The Level of the highest ACT during PCI will be compared between the groups
Time Frame
At the end of PCI
Title
Number of Patients With Minor Bleeding Complications
Description
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
Title
Number of Patients With Minor Bleeding Complications
Description
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
Title
Number of Patients With Major Bleeding Complications
Description
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
Title
Number of Patients With Major Bleeding Complications
Description
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
Title
Number of Patients With Negative Clinical Outcomes
Description
The rates of death, myocardial infarction, and revascularization at 1-year post-PCI.
Time Frame
At 1-year post-PCI
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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%.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Massoud Leesar, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31766977
Citation
Marian MJ, Abu Daya H, Chatterjee A, Al Solaiman F, Sasse MF, Fonbah WS, Workman RW, Johnson BE, Carlson SE, Brott BC, Prabhu SD, Leesar MA. Effects of Crushed Ticagrelor Versus Eptifibatide Bolus Plus Clopidogrel in Troponin-Negative Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Randomized Clinical Trial. J Am Heart Assoc. 2019 Dec 3;8(23):e012844. doi: 10.1161/JAHA.119.012844. Epub 2019 Nov 26.
Results Reference
derived
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Crushed Ticagrelor Versus Eptifibatide Bolus + Clopidogrel
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