Comparison of Antiplatelet Effect of Ticagrelor vs Tirofiban in Patients With Non-ST Elevation Acute Coronary Syndrome

Phase 3

• Conditions: Non-ST Segment Elevation Acute Coronary Syndrome
• Interventions: Drug: Ticagrelor; Drug: Tirofiban

• Registration Number: NCT01660373
• Lead Sponsor: Pusan National University Yangsan Hospital

Brief Summary

This is a single-center, open-label prospective randomized pharmacodynamic investigation of two anti platelet regimens in patients who are planned to undergo PCI for non-ST segment elevation acute coronary syndrome(NSTE-ACS) for 24 hours

1. Ticagrelor : loading dose(180mg) followed by maintenance dose(90mg bid)

2. Tirofiban : 0.4ug/kg/min for 30min followed by 0.1ug/kg/min

* both agents will be given on top of aspirin

Detailed Description

In combination with aspirin, P2Y12 receptor antagonist or glycoprotein IIb/IIIa inhibitor(GPI) is now a recommended drug as the standard dual antiplatelet regimen in patients with acute coronary syndrome(1).

Ticagrelor is a newly developed oral P2Y12 receptor inhibitor. It shows faster, greater and more consistent platelet inhibition as compared with previous P2Y12 receptor antagonist clopidogrel(2) and it also shows better clinical outcome and similar risk for bleeding as compared with clopidogrel(3).Interestingly, pharmacodynamic data of some studies showed excellent effect of ticagrelor in terms of inhibiting platelet activation apparently as high as that of GPI(2,4).

Primary hypothesis: Ticagrelor have a comparable efficacy in platelet inhibition to GPI in patients with non-ST segment elevation acute coronary syndrome.

Statistical design : non-inferiority test

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-08-05
• Study First Submitted QC: 2012-08-07
• Study First Posted: 2012-08-08
• Status Verified: 2012-12
• Last Update Submitted: 2012-12-16
• Last Update Posted: 2012-12-18
• Primary Completion: 2013-08
• Study Completion: 2013-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients with recent or current ischemic symptoms at the time of randomization will be eligible if 2 of the following criteria are met: ST-T change indicating ischemia; a positive test of biomarker indication 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)

Exclusion Criteria

1. Administration of fibrinolytic or any GP IIb/IIIa inhibitors for the treatment of current AMI
2. Major surgery or trauma within 30 days
3. Active bleeding
4. Previous stroke in the last six months
5. Oral anticoagulant therapy
6. Pre-existing thrombocytopenia
7. Vasculitis
8. Hypertensive retinopathy
9. Severe hepatic failure
10. Severe renal failure requiring hemodialysis
11. Documented allergy/intolerance or contraindication to tirofiban or P2Y12 inhibitor
12. Uncontrolled hypertension (systolic or diastolic arterial pressure >180 mmHg or 120, respectively, despite medical therapy)
13. Limited life expectancy, e.g. neoplasms, others
14. Inability to obtain informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ticagrelor	Ticagrelor	loading dose(180mg) followed by maintenance dose(90mg bid)
Tirofiban	Tirofiban	0.4ug/kg/min for 30min followed by 0.1ug/kg/min

Primary Outcome Measures

Name	Time	Method
Percentage IPA after 20µmol/l ADP at 2 hour	2 hours	Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP and aggregation will be assessed using a light transmittance aggregometer(Chronolog, USA).

Secondary Outcome Measures

Name	Time	Method
Percentage IPA at 8 hours after 20µMol ADP, TRAP, Arachidonic acid, Collagen	24 hours	Blood samples with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with 20 µmol/l ADP, TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).
periprocedural bleeding	0~24 hours	Periprocedural bleeding will be monitored and described according to BARC and TIMI definition
Peak cardiac enzyme level	0~24 hours	From blood samples at 0, 2H, 8H and 24H, CK-MB and Troponin I will be measured
Percentage IPA after TRAP, arachidonic acid, collagen at 2 hours	2 hours	Blood samples anticoagulated with 0.129 mol/l sodium citrate will be collected for platelet reactivity. Platelet-rich plasma, obtained by centrifuging whole blood for 15 min at 100 g, will be stimulated with TRAP, arachidonic acid and collagen and aggregation will be assessed using a light transmittance aggregometer(Chrono-log, USA).

Trial Locations

Locations (1)

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Kyeongsangnamdo, Korea, Republic of