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

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
C. Michael Gibson, MS, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00604695
First received: January 7, 2008
Last updated: August 6, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Acute Myocardial Infarction
Drug: Tenecteplase
Drug: Sterile Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Trial Evaluating Low-Dose IntraCoronary AdjunctivE Tenecteplase During Primary PCI for ST-Elevation Myocardial Infarction (ICE T)

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

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 [ Time Frame: Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug ] [ Designated as safety issue: No ]
    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) [ Time Frame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug ] [ Designated as safety issue: No ]
    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 [ Time Frame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug ] [ Designated as safety issue: No ]
    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 [ Time Frame: Through 30days following PPCI ] [ Designated as safety issue: Yes ]
  • Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding [ Time Frame: Through 30days following primary percutaneous coronary intervention ] [ Designated as safety issue: Yes ]
  • Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias [ Time Frame: Through 30days following primary percutaneous coronary intervention ] [ Designated as safety issue: Yes ]
  • Safety Endpoint: Number of Deaths [ Time Frame: Through 30days following primary percutaneous coronary intervention ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: July 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Two (4mg) doses of tenecteplase
Drug: Tenecteplase
Intracoronary injection of IV tenecteplase.
Placebo Comparator: 2
Two (4mL) doses of sterile saline
Drug: Sterile Saline
Intracoronary injection of IV sterile saline

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.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00604695

Locations
United States, Florida
Northeast Georgia Heart Center, PC
Gainesville, Florida, United States, 30501
United States, Georgia
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
Atlanta VA Medical Center
Decatur, Georgia, United States, 30033
Emory University
Decatur, Georgia, United States, 30033
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Crittenton Hospital Medical Center
Rochester, Michigan, United States, 48307
United States, Nebraska
Heart Consultants, PC
Freemont, Nebraska, United States, 68025
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
C. Michael Gibson, MS, MD
Genentech
Investigators
Principal Investigator: C. Michael Gibson, MS, MD Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: C. Michael Gibson, MS, MD, Sponsor-Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00604695     History of Changes
Other Study ID Numbers: N3770S
Study First Received: January 7, 2008
Results First Received: May 15, 2012
Last Updated: August 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Brigham and Women's Hospital:
ST-Elevation Myocardial Infarction
Acute Myocardial Infarction
No Reflow

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Tenecteplase
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on July 28, 2014