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

Sponsor:	C. Michael Gibson, MS, MD
Collaborator:	Genentech
Information provided by (Responsible Party):	C. Michael Gibson, MS, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00604695

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 II

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:

MedlinePlus related topics: Angioplasty Heart Attack

Drug Information available for: Tenecteplase

U.S. FDA Resources

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

Primary Outcome Measures:

angiographic characteristics of the culprit lesion [ Time Frame: Prior to index hospitalization discharge and at 30 days. ] [ 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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	40
Study Start Date:	July 2008
Estimated Study Completion Date:	November 2011
Estimated 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

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
Last Updated:	September 26, 2011
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 February 09, 2012