Antiplatelet Effects of Tirofiban vs. Cangrelor N-STEMI Patients Undergoing Percutaneous Coronary Intervention

Comparison of Pharmacodynamic Effects of Tirofiban vs. Cangrelor in N-STEMI Patients Undergoing Percutaneous Coronary Intervention

Immediate potent inhibition of platelet function is critical for the prevention of periprocedural ischemic event occurrences in high risk N-ST segment elevation myocardial infarction (NSTEMI) in patients undergoing percutaneous coronary intervention (PCI). Currently, dual antiplatelet therapy with aspirin and an oral P2Y12 receptor blocker (with loading doses) is widely used for PCI. However, immediate, potent and reversible inhibition of platelet aggregation is not possible even with the newer oral agents, prasugrel and ticagrelor. Therefore, an intravenously administered GPIIb/IIIa receptor inhibitor (tirofiban) or P2Y12 receptor blocker (cangrelor) with fast onset and offset of actions will provide more desired antiplatelet effects in the setting of PCI. This study will measure and compare the anti-platelet effects of Tirofiban and Cangrelor in patients presenting with N-STEMI and undergoing PCI.

Study Overview

• Status: Terminated
• Conditions: Non-ST Elevation Myocardial Infarction (NSTEMI)
• Intervention / Treatment: Drug: Tirofiban; Drug: Cangrelor

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

• Study Contact: Name: Kevin Bliden, BS, MBA; Phone Number: 703-776-7702; Email: kevin.bliden@inova.org

Study Locations

• United States
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Health Care System

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This study will consist of NSTEMI patients undergoing percutaneous coronary intervention (PCI): 30 patients each will be treated with tirofiban or cangrelor (total n=60).

Description

Inclusion Criteria:

1. NSTEMI meeting the following criteria:

1. Patients 18 years of age or older with one or more of the following symptoms:

   • new ST-segment depression or transient elevation of at least 1 mm
   • elevations in troponin I, troponin T, or creatine kinase MB levels above ULN
2. Eligible for ticagrelor, cangrelor, aspirin, UFH, and GP IIb/IIIa inhibitor treatment.
3. Admitted at cardiac catheterization laboratory hospital or associated facility.
4. Competent mental condition to provide informed consent.

Exclusion Criteria:

1. Unstable angina, STEMI
2. Cardiogenic shock
3. Refractory ventricular arrhythmias
4. New York Heart Association class IV congestive heart failure
5. Cardiac arrest within 1 week of study entry
6. History of hemorrhagic or ischemic stroke, TIA, sub-arachnoid hemorrhage or intracranial neoplasm, arteriovenous malformation, or aneurysm
7. Fibrinolytic therapy within 48 hours of study entry
8. Active pathological bleeding or history of bleeding diathesis
9. Severe hepatic insufficiency
10. Current peptic ulceration
11. Increased bleeding risk, per investigator judgment
12. Known anemia (hematocrit<25%)/thrombocytopenia (platelet count < 100,000mm3)
13. Surgery within 4 weeks before study entry or planned surgery within 2 months after study entry
14. Any P2Y12 receptor inhibitor or GP IIb/IIIa inhibitor within 7 days of study entry
15. Receiving warfarin or other coumadin derivatives or NOACs within the last 10 days with an INR >1.5 secs or planned use during the hospitalization period
16. Contraindication to the use of ticagrelor and/or aspirin
17. Receiving or will receive oral anticoagulation or other oral antiplatelet therapy (except aspirin) that cannot be safely discontinued within the next 3 months
18. Receiving daily NSAIDs or COX2 inhibitors that cannot be discontinued or anticipated to require >2 weeks of daily NSAIDs or COX2 inhibitors during study
19. Investigational drug in last 30 days or presently enrolled in drug/device study
20. Women of childbearing potential (post-menopausal women can be enrolled if at least 1 year of amenorrhea or surgically sterile)
21. Condition associated with poor treatment compliance (e.g., alcoholism, mental illness, or drug dependence)
22. Inability to provide written informed consent and to understand the full meaning of the informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tirofiban Therapy; patients randomized to tirofiban therapy	Drug: Tirofiban; Patients will receive Tirofiban during the PCI procedure; Other Names: Aggrastat
Cangrelor Therapy; patients randomized to cangrelor therapy	Drug: Cangrelor; Patients will receive Cangrelor during the PCI procedure; Other Names: Kengreal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombin Receptor Activator Peptide (TRAP) Induced Platelet Aggregation (%)	Assessment of platelet aggregation (%) in response to 10uM thrombin receptor activator peptide. Normal reference range is 60-100% aggregation.	30 minutes post-start of the infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adenosine Diphosphate (ADP) Induced Platelet Aggregation (%)	Assessment of platelet aggregation (%) in response to 20uM ADP at baseline and serially following tirofiban or cangrelor infusion. Normal reference range is 60-100% aggregation.	30 minutes post-start of the infusion
Thrombin Induced Platelet-fibrin Clot Strength (mm)	Assessment of thrombin induced platelet-fibrin clot strength (mm) by thromboelastography (TEG6S). Normal reference range is 55-68 mm	30 minutes post-start of the infusion
Shear-induced Thrombus Formation (AUC)	Real time evaluation of shear-induced thrombus formation using novel RUO T-TAS plus system. AUC is calculated as time to reach 60 kPa	30 minutes after the end of the infusion.

Collaborators and Investigators

• Sponsor: Inova Health Care Services
• Investigators: Principal Investigator: Paul Gurbel, MD, Inova Health Care Services

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2017
• Primary Completion (Actual): June 27, 2019
• Study Completion (Actual): June 27, 2019

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimated): February 9, 2017

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Non-ST Elevated Myocardial Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Tirofiban; Cangrelor
• Other Study ID Numbers: 17-2617

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No