Clinical trial NCT00604695: A Safety/Efficacy Study of Intra-coronary Tenecteplase During Balloon Angioplasty to Treat Heart Attacks
Official title: A Randomized Trial Evaluating Low-Dose IntraCoronary AdjunctivE Tenecteplase During Primary PCI for ST-Elevation Myocardial Infarction (ICE T)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Keywords: ST-Elevation Myocardial Infarction
Acute Myocardial Infarction
No Reflow
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-01-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention
timeFrame: Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention
Secondary outcomes:
measure: 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
timeFrame: Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention
measure: 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
timeFrame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
measure: Measurements of Flow Velocity in the Culprit Artery in Terms of Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC)
timeFrame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
measure: 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
timeFrame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
measure: Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding
timeFrame: Through 30days following PPCI
measure: Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding
timeFrame: Through 30days following primary percutaneous coronary intervention
measure: Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias
timeFrame: Through 30days following primary percutaneous coronary intervention
measure: Safety Endpoint: Number of Deaths
timeFrame: Through 30days following primary percutaneous coronary intervention
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Northeast Georgia Heart Center, PC
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Decatur
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Crittenton Hospital Medical Center
state: Michigan
city: Freemont
country: United States
facility: Heart Consultants, PC
state: Nebraska
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Brigham and Women's Hospital
name: C. Michael Gibson, MS, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.