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

Acute Myocardial Infarction Clinical Trial

— ICE T-TIMI 49  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00604695
• Other study ID #: N3770S
• Status: Completed
• Phase: Phase 2
• First received: January 7, 2008
• Last updated: August 6, 2012
• Start date: July 2008
• Est. completion date: November 2011

Study information

• Verified date: August 2012
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Tenecteplase
Intracoronary injection of IV tenecteplase.
• Sterile Saline
Intracoronary injection of IV sterile saline

Locations

Country	Name	City	State
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Emory University	Decatur	Georgia
United States	Heart Consultants, PC	Freemont	Nebraska
United States	Northeast Georgia Heart Center, PC	Gainesville	Florida
United States	Crittenton Hospital Medical Center	Rochester	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
C. Michael Gibson, MS, MD	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding		Through 30days following PPCI	Yes
Secondary	Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding		Through 30days following primary percutaneous coronary intervention	Yes
Secondary	Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias		Through 30days following primary percutaneous coronary intervention	Yes
Secondary	Safety Endpoint: Number of Deaths		Through 30days following primary percutaneous coronary intervention	Yes