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

January 7, 2008
August 6, 2012
July 2008
November 2011   (final data collection date for primary outcome measure)
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 ]
  • angiographic characteristics of the culprit lesion [ Time Frame: Prior to index hospitalization discharge and at 30days. ] [ Designated as safety issue: Yes ]
  • measurements of epicardial flow and myocardial perfusion in the territory of the infarct-related artery [ Time Frame: At the time of catheterization for the STEMI. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00604695 on ClinicalTrials.gov Archive Site
  • 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 ]
Safety endpoints including the incidence of death, recurrent MI, abrupt vessel closure, subacute stent thrombosis, and TIMI Major and Minor Bleeding [ Time Frame: At hospital discharge and at 30days. ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Safety/Efficacy Study of Intra-coronary Tenecteplase During Balloon Angioplasty to Treat Heart Attacks
A Randomized Trial Evaluating Low-Dose IntraCoronary AdjunctivE Tenecteplase During Primary PCI for ST-Elevation Myocardial Infarction (ICE T)

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myocardial Infarction
  • Drug: Tenecteplase
    Intracoronary injection of IV tenecteplase.
  • Drug: Sterile Saline
    Intracoronary injection of IV sterile saline
  • Active Comparator: 1
    Two (4mg) doses of tenecteplase
    Intervention: Drug: Tenecteplase
  • Placebo Comparator: 2
    Two (4mL) doses of sterile saline
    Intervention: Drug: Sterile Saline
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
November 2011
November 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00604695
N3770S
Yes
C. Michael Gibson, MS, MD, Brigham and Women's Hospital
C. Michael Gibson, MS, MD
Genentech
Principal Investigator: C. Michael Gibson, MS, MD Brigham and Women's Hospital
Brigham and Women's Hospital
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP