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

Primary Purpose

Acute Myocardial Infarction

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tenecteplase
Sterile Saline
Sponsored by
C. Michael Gibson, MS, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myocardial Infarction focused on measuring ST-Elevation Myocardial Infarction, Acute Myocardial Infarction, No Reflow

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Northeast Georgia Heart Center, PC
  • Emory University Hospital Midtown
  • Atlanta VA Medical Center
  • Emory University
  • Beth Israel Deaconess Medical Center
  • Crittenton Hospital Medical Center
  • Heart Consultants, PC
  • University of North Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

Two (4mg) doses of tenecteplase

Two (4mL) doses of sterile saline

Outcomes

Primary Outcome Measures

Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention

Secondary Outcome Measures

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
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
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
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
Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding
Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding
Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias
Safety Endpoint: Number of Deaths

Full Information

First Posted
January 7, 2008
Last Updated
August 6, 2012
Sponsor
C. Michael Gibson, MS, MD
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00604695
Brief Title
A Safety/Efficacy Study of Intra-coronary Tenecteplase During Balloon Angioplasty to Treat Heart Attacks
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
C. Michael Gibson, MS, MD
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction
Keywords
ST-Elevation Myocardial Infarction, Acute Myocardial Infarction, No Reflow

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Two (4mg) doses of tenecteplase
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Two (4mL) doses of sterile saline
Intervention Type
Drug
Intervention Name(s)
Tenecteplase
Intervention Description
Intracoronary injection of IV tenecteplase.
Intervention Type
Drug
Intervention Name(s)
Sterile Saline
Intervention Description
Intracoronary injection of IV sterile saline
Primary Outcome Measure Information:
Title
Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention
Time Frame
Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention
Secondary Outcome Measure Information:
Title
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
Time Frame
Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention
Title
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
Description
Thrombolysis In Myocardial Infarction (TIMI) Myocardial Perfusion Grade (TMPG) of 2 or 3 in the territory of the culprit artery
Time Frame
Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
Title
Measurements of Flow Velocity in the Culprit Artery in Terms of Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC)
Description
Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) in the culprit artery
Time Frame
Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
Title
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
Description
Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) of less than 14
Time Frame
Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
Title
Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding
Time Frame
Through 30days following PPCI
Title
Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding
Time Frame
Through 30days following primary percutaneous coronary intervention
Title
Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias
Time Frame
Through 30days following primary percutaneous coronary intervention
Title
Safety Endpoint: Number of Deaths
Time Frame
Through 30days following primary percutaneous coronary intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
C. Michael Gibson, MS, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northeast Georgia Heart Center, PC
City
Gainesville
State/Province
Florida
ZIP/Postal Code
30501
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Atlanta VA Medical Center
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Emory University
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Crittenton Hospital Medical Center
City
Rochester
State/Province
Michigan
ZIP/Postal Code
48307
Country
United States
Facility Name
Heart Consultants, PC
City
Freemont
State/Province
Nebraska
ZIP/Postal Code
68025
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31870492
Citation
Gibson CM, Kumar V, Gopalakrishnan L, Singh P, Guo J, Kazziha S, Devireddy C, Pinto D, Marshall JJ, Stouffer GA, Mavromatis K, Grip L, Bainey KR; TIMI & PERFUSE Study Group. Feasibility and Safety of Low-Dose Intra-Coronary Tenecteplase During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction (ICE T-TIMI 49). Am J Cardiol. 2020 Feb 15;125(4):485-490. doi: 10.1016/j.amjcard.2019.11.018. Epub 2019 Nov 20.
Results Reference
derived

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

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