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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: tirofiban intracoronary bolus-only; Drug: tirofiban intravenous bolus plus infusion

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kosuyolu Heart Hospital
• Collaborators: The Society of Cardiac Health Protection
• Investigators: Study Chair: Cevat Kırma, Assoc.Prof, Kosuyolu Heart and Research Hospital; Principal Investigator: Ayhan Erkol, M.D, Kosuyolu Heart and Research Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: April 21, 2010
• First Submitted That Met QC Criteria: April 21, 2010
• First Posted (Estimate): April 22, 2010

Study Record Updates

• Last Update Posted (Estimate): April 22, 2010
• Last Update Submitted That Met QC Criteria: April 21, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: microcirculation; tirofiban; primary angioplasty
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Tirofiban
• Other Study ID Numbers: 33