A Safety/Efficacy Study of Intra-coronary Tenecteplase During Balloon Angioplasty to Treat Heart Attacks (ICE T-TIMI 49)

C. Michael Gibson, MS, MD

Status and phase: Completed; Phase 2

Conditions: Acute Myocardial Infarction

Treatments: Drug: Tenecteplase; Drug: Sterile Saline

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00604695

N3770S

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups, including a placebo group

1

Active Comparator group

Description:

Two (4mg) doses of tenecteplase

Treatment:

Drug: Tenecteplase

2

Placebo Comparator group

Description:

Two (4mL) doses of sterile saline

Treatment:

Drug: Sterile Saline