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

NCT ID: NCT00604695

Last Updated: 2012-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2011-11-30

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.

Conditions

Acute Myocardial Infarction

Keywords

ST-Elevation Myocardial Infarction; Acute Myocardial Infarction; No Reflow

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Two (4mg) doses of tenecteplase

Group Type: ACTIVE_COMPARATOR

Tenecteplase

Intervention Type: DRUG

Intracoronary injection of IV tenecteplase.

2

Two (4mL) doses of sterile saline

Group Type: PLACEBO_COMPARATOR

Sterile Saline

Intervention Type: DRUG

Intracoronary injection of IV sterile saline

Interventions

Tenecteplase

Intracoronary injection of IV tenecteplase.

Intervention Type: DRUG

Sterile Saline

Intracoronary injection of IV sterile saline

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

C. Michael Gibson, MS, MD

OTHER

Sponsor Role: lead

Responsible Party

C. Michael Gibson, MS, MD

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

C. Michael Gibson, MS, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Northeast Georgia Heart Center, PC

Gainesville, Florida, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Atlanta VA Medical Center

Decatur, Georgia, United States

Emory University

Decatur, Georgia, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Crittenton Hospital Medical Center

Rochester, Michigan, United States

Heart Consultants, PC

Freemont, Nebraska, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31870492 (View on PubMed)

Other Identifiers

N3770S

Identifier Type: -

Identifier Source: org_study_id