A Safety/Efficacy Study of Intra-coronary Tenecteplase During Balloon Angioplasty to Treat Heart Attacks

Study Overview
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Brief Summary
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The primary objective of this study is to gather preliminary data regarding the angiographic efficacy of the administration of low-dose adjunctive intracoronary (IC) tenecteplase during balloon angioplasty for heart attacks. We hypothesize that low-dose IC tenecteplase will enhance the breakdown of blood clots at the site of the culprit lesion leading to reduced damage to the heart muscle.

Detailed Description
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The primary objective of this study is to gather preliminary data regarding the angiographic efficacy of the administration of low-dose adjunctive intracoronary (IC) tenecteplase during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Efficacy will be assessed by measurements of both the angiographic characteristics of the culprit lesion as well as by measurements of epicardial flow and myocardial perfusion in the territory of the infarct-related artery. This study will also evaluate the safety of administering low-dose IC tenecteplase to subjects undergoing primary PCI for STEMI treated with standard therapy (aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors). Safety endpoints include the incidence of death, recurrent myocardial infarction (MI), abrupt vessel closure, subacute stent thrombosis, and TIMI major and minor bleeding events. Prompt reperfusion therapy with primary PCI in patients with STEMI improves clinical outcomes through salvage of myocardial tissue. The proposed pilot trial is a randomized, placebo-controlled trial to evaluate the effectiveness and safety of adjunctive low-dose IC tenecteplase in conjunction with standard medical therapy during primary PCI for STEMI. We hypothesized that low-dose IC tenecteplase will enhance fibrinolysis at the site of the culprit lesion leading to reduced microvascular dysfunction. As reduced dose tenecteplase will be injected directly into the coronary artery increasing local concentration of the drug with minor systemic effects, an improved safety profile is also expected from this mode of administration.

Official Title
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A Randomized Trial Evaluating Low-Dose IntraCoronary AdjunctivE Tenecteplase During Primary PCI for ST-Elevation Myocardial Infarction (ICE T)

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Tenecteplase
* Drug: Sterile Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects (men or women) at least 18 years and less than 75 years of age and Ischemic discomfort ≥20 minutes and ≤6 hours of duration and ST elevation ≥1mm (≥0.1mV) in two contiguous limb leads OR ≥2mm (≥0.2mV) in two contiguous precordial leads and Occluded infarct-related artery (TIMI Flow Grade 0 or 1) at the time of coronary angiography and Planned primary PCI within 2 hours of hospital presentation and Planned or concomitant use of aspirin, clopidogrel, unfractionated heparin, and Glycoprotein IIb/IIIa inhibition with intent to stent the infarct-related artery and Informed consent able to be obtained Exclusion Criteria: CLINICAL Age ≥75 years Maximal systolic blood pressure <80 mmHg AFTER initial fluid and/or pressor resuscitation. Uncontrolled hypertension (SBP >180 OR DBP >110) at time of enrollment. Cardiac arrest or arrhythmia requiring chest compressions or cardiopulmonary resuscitation. Known pregnancy. BIOCHEMICAL Known thrombocytopenia (platelet count <100,000) Known severe renal insufficiency (creatinine >4.0 mg/dL). INCREASED BLEEDING RISK Active internal bleeding Recent (<3 months) gastrointestinal hemorrhage Recent intracranial or intraspinal surgery, trauma, major surgery, or biopsy of a parenchymal organ (< 1 month) Known coagulopathy, platelet disorder, or history of thrombocytopenia Current warfarin therapy Known neoplasm Any known history of transient ischemic attack, cerebrovascular accident, or active intracranial pathology including arteriovenous malformation or aneurysm MEDICATIONS Administration of a fibrinolytic agent within 72 hours Known allergy or contraindication to fibrinolytics OR aspirin OR heparin OR clopidogrel ANGIOGRAPHIC Left Main Coronary artery culprit lesion Ostial culprit lesion (ostium of LAD, LCX, or RCA). Lesion in non-native coronary artery (e.g. saphenous vein graft, arterial conduit graft) Subjects requiring urgent coronary artery bypass grafting

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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 |
| --- | --- |
| Active Comparator: 1<br>Two (4mg) doses of tenecteplase | Drug: Tenecteplase<br>* Intracoronary injection of IV tenecteplase.<br>|
| Placebo Comparator: 2<br>Two (4mL) doses of sterile saline | Drug: Sterile Saline<br>* Intracoronary injection of IV sterile saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention |  | Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Decrease in Thrombus Grade in the Culprit Artery Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention |  | Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention | 
| Number of Patients With Thrombolysis In Myocardial Infarction (TIMI) Myocardial Perfusion Grade (TMPG) of 2 or 3 in the Territory of the Culprit Artery Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | Thrombolysis In Myocardial Infarction (TIMI) Myocardial Perfusion Grade (TMPG) of 2 or 3 in the territory of the culprit artery | Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | 
| Measurements of Flow Velocity in the Culprit Artery in Terms of Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) | Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) in the culprit artery | Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | 
| Number of Patients With Hyperemic Flow in the Culprit Artery. That is Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) of Less Than 14 | Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) of less than 14 | Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | 
| Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding |  | Through 30days following PPCI | 
| Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding |  | Through 30days following primary percutaneous coronary intervention | 
| Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias |  | Through 30days following primary percutaneous coronary intervention | 
| Safety Endpoint: Number of Deaths |  | Through 30days following primary percutaneous coronary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ST-Elevation Myocardial Infarction, Acute Myocardial Infarction, No Reflow