Tirofiban Intracoronary Bolus-only Versus Intravenous Bolus Plus Infusion in STEMI Patients

Study Overview
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Brief Summary
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The aim of this randomized trial is to compare the efficacy of high dose tirofiban administered as either an intracoronary bolus alone or as an intravenous bolus followed by a maintenance infusion with respect to microvascular perfusion and long term left ventricular infarct size, volumes and function.

Detailed Description
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Primary percutaneous coronary intervention (PCI) is currently the treatment of choice for patients with acute ST elevation myocardial infarction (STEMI). Nevertheless, despite restoration of normal epicardial flow, myocardial perfusion remains impaired in approximately half of patients and is associated with a poor prognosis. A variety of invasive and non-invasive techniques have been proposed to evaluate microvascular perfusion and several invasive hemodynamic measures have been closely associated with microvascular damage.In order to improve microvascular perfusion after primary PCI, a variety of treatment strategies have been developed, such as adjunctive administration of glycoprotein IIb/IIIa inhibitors (GPIs). Although current ACC/AHA guidelines recommend that small molecule GPIs should be administered as a bolus followed by 18 hours of continuous infusion, changes in clinical practice may obviate the need for a maintenance infusion in current practice. We hypothesized that when tirofiban is administered via intracoronary route, a bolus-only strategy may even be superior to intravenous bolus plus infusion strategy in maintaining myocardial perfusion. In order to evaluate microvascular function, we used a guidewire tipped with pressure and temperature sensors and measured the coronary hemodynamic parameters, as the index of microvascular resistance and coronary flow reserve, measures which have been closely associated with microvascular damage. In order to increase the predictive value of these indices, we performed these measurements four to five days after MI, because it has been shown that the extent of microvascular dysfunction changes, particularly within first 48 hours after reperfusion and stabilizes between 2 days and 1 week after perfusion

Official Title
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Prospective Randomized Controlled Clinical Study to Compare Tirofiban Intracoronary Bolus-Only vs Intravenous Bolus Plus Infusion in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: tirofiban intracoronary bolus-only
* Drug: tirofiban intravenous bolus plus infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Typical ongoing ischemic chest pain for longer than 30 minutes ST segment elevation of 0,1 mV or greater in at least two contiguous leads or a new left bundle branch block on the initial ECG. Exclusion Criteria: Cardiogenic shock and / or clinical instability previous STEMI Malignant life threatening diseases Presence of an additional lesion causing more than 50% narrowing distal to the culprit lesion Contraindications to aspirin, clopidogrel, or heparin inability to give informed consent.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirofiban intracoronary bolus-only<br>Tirofiban bolus administered via intracoronary route at the time of primary PCI with no additional peri/postprocedural maintenance infusion | Drug: tirofiban intracoronary bolus-only<br>* administer tirofiban bolus intracoronary during primary percutaneous coronary intervention with no additional maintenance infusion<br>* Other names: Aggrastat;|
| Active Comparator: Tirofiban intravenous bolus+infusion<br>Tirofiban bolus administered intravenously before PCI, followed by periprocedural maintenance infusion | Drug: tirofiban intravenous bolus plus infusion<br>* administer tirofiban bolus intravenously and maintain infusion for up to 18 hours<br>* Other names: Aggrastat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Indices of microvascular perfusion | Intracoronary hemodynamic measures of index of microvascular resistance and coronary flow reserve | Post-PCI day 4 to 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ST segment resolution |  | post-PCI 90. minute | 
| corrected TIMI frame count |  | immediately after PCI, post-PCI day 4 to 5 | 
| Myocardial Blush Grade |  | immediately after PCI, post-PCI day 4 to 5 | 
| Scintigraphic infarct size | Left ventricular infarct size by SPECT | 6th month | 
| Changes in left ventricular volume | Measured with echocardiography by using modified Simpson's method | Post-PCI day 3- 6th month | 
| Composite of major adverse cardiovascular events | composite of reinfarction, target vessel revascularization and death. | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary angioplasty, tirofiban, microcirculation