Study of Tirofiban Administration in Patients With Aspirin and or Clopidogrel Resistance

Study Overview
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Brief Summary
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This study will evaluate whether adding tirofiban, administered at high bolus dose on top of aspirin and clopidogrel will lead to a lower rate of periprocedural myocardial infarction after percutaneous coronary intervention in elective patients presenting with aspirin and/or clopidogrel resistance.

Detailed Description
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This study will investigate the effect of treatment with a high bolus dosage of Tirofiban (in addition to Aspirin, Heparin and 300mg or 600mg clopidogrel) on the rate of periprocedural myocardial infarction compared to Aspirin, Heparin (or bivalirudin) and 300mg or 600mg clopidogrel alone in patients resistant to aspirin and/or to clopidogrel. This is a randomized, double blind, placebo controlled (with bailout tirofiban as rescue) multicenter study. Enrollment will last between 12 and 36 months depending on the final number of participating centres. The minimum follow-up will be 30 days after the index procedure.

Official Title
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Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel

Conditions
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Angioplasty, Transluminal, Percutaneous Coronary

Intervention / Treatment
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* Drug: Tirofiban
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Patients older than 18 years scheduled for coronary angiography and/or PCI will be enrolled. [Patients should be CK-MB negative (to avoid CK washout with revascularization) and also cTnI/T negative whereas other high-risk features will not lead to patient exclusion. All consecutive patients with stable or unstable troponin and CK-MB negative coronary artery disease showing aspirin and or clopidogrel resistance (ACR) will be enrolled. These include: Patients with clinical indication to undergo angiography for possible revascularisation. Patients with ACR in whom catheter-based coronary intervention is planned based on previous angiogram. Exclusion Criteria: Patients who can not give informed consent or have a life expectancy of < 1 year Evolving or Ongoing myocardial infarction (MI) (Persistence of or developing Q wave or ST segment elevation at ECG with or without typical chest pain or typical rapid rise and fall CK-MB or new LBBB) or patients in whom the treating physician intends to use a Gp IIB/IIIa inhibitors. Administration of any GP IIb/IIIa receptor antagonist, anticoagulation, or lytic therapy in the previous 30 days Serum creatinine more than 2.5 mg/dl (221 micromol/L) Ongoing bleeding or bleeding diathesis or contraindication for anticoagulation or increase bleeding risk or history of bleeding in the last 1 year Previous stroke or TIA or any intracranial pathology in the last six months Major surgery or trauma within the previous six weeks Platelet count < 100.000 per cubic mm or HCT ,33% or Hb < 11 gm/dL Subjects who received low-molecular-weight heparin within the 24 hours prior to randomization Subjects with an allergy or intolerance to aspirin, heparin, clopidogrel, or tirofiban Patients with severe hypertension (SBP > 180 mm Hg or DBP > 110 mm Hg) or in cardiogenic shock (SBP 80 mm Hg or below for > 30 minutes) or requiring IABP

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Aspirin, clopidogrel, Unfractioned heparin or bivalirudin plus tirofiban infusion given at high bolus dose | Drug: Tirofiban<br>* Tirofiban infusion given as high bolus dose plus standard 14-24 hour infusion<br>* Other names: Glycoprotein IIb/IIIa inhibitor;|
| Placebo Comparator: 2<br>Aspirin, clopidogrel, Unfractioned heparin or bivalirudin plus placebo | Drug: Placebo<br>* Saline infusion will be administered for 14-24 hours<br>* Other names: Glycoprotein IIb/IIIa inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin I or T elevation ratio at least three times the upper limit of normal. |  | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of myocardial infarction defined as elevation of CK-MB >1, ≥3 or ≥5 times the ULN in one or more blood sample(s). |  | 30 days | 
| Elevation of troponin levels above upper limit of normal in ratios different from the primary endpoint |  | within 30 days | 
| Bleeding rates |  | 30 days | 
| Stent thrombosis |  | with the first year of follow-up | 
| The rate of major adverse cardiovascular events |  | at 30 days and 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tirofiban, aspirin resistance, clopidogrel resistance