Crushed Ticagrelor Versus Eptifibatide Bolus + Clopidogrel

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Angina, Unstable
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor; Drug: Eptifibatide

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Massoud Leesar, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): January 30, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 6, 2016

Study Record Updates

• Last Update Posted (Actual): May 4, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Acute Coronary Syndrome; Angina, Unstable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel; Eptifibatide
• Other Study ID Numbers: F151006002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No