Acute Myocardial Infarction
Conditions
Keywords
ST-Elevation Myocardial Infarction, Acute Myocardial Infarction, No Reflow
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.
Interventions
DRUGTenecteplase
Intracoronary injection of IV tenecteplase.
DRUGSterile Saline
Intracoronary injection of IV sterile saline
Sponsors
Genentech, Inc.
C. Michael Gibson, MS, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention | Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | 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) | Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | 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 | Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug | Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) of less than 14 |
| 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 | Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention | — |
| Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding | Through 30days following primary percutaneous coronary intervention | — |
| Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias | Through 30days following primary percutaneous coronary intervention | — |
| Safety Endpoint: Number of Deaths | Through 30days following primary percutaneous coronary intervention | — |
| Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding | Through 30days following PPCI | — |
Countries
United States
Participant flow
Recruitment details
The study randomized 40 primary percutaneous coronary intervention (PPCI) patients from 6 hospitals in the United States. The patients were given either a volume matched bolus of intracoronary (IC) tenecteplase (TNK) (4 mg; n=20) or IC saline placebo (4 mg; n=16) before and following PPCI. 4 subjects were randomized but did not receive 1st bolus.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Two (4mg) doses of tenecteplase | 20 |
| Placebo Control Two (4mL) doses of sterile saline | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive first bolus. | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo Control | Active Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 17 Participants | 35 Participants |
| Age Continuous | 55.6 years STANDARD_DEVIATION 8.9 | 55.2 years STANDARD_DEVIATION 7.6 | 55.4 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 17 Participants | 15 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 20 | 11 / 16 |
| serious Total, serious adverse events | 2 / 20 | 1 / 16 |
Outcome results
Primary
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
Population: Of the 20 patients randomized to the treatment arm, 4 patients did not meet the inclusion criteria of Thrombolysis In Myocardial Infarction (TIMI) Flow Grade(TFG) 0/1.~Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo) and 3 patients did not meet the inclusion criteria of TFG 0/1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Treatment | Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention | 100 Percent diameter stenosis |
| Placebo Control | Percent Diameter Stenosis of the Culprit Lesion Following the First Bolus of Study Drug Prior to Primary Percutaneous Coronary Intervention | 100 Percent diameter stenosis |
Secondary
Measurements of Flow Velocity in the Culprit Artery in Terms of Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC)
Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) in the culprit artery
Time frame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
Population: Of the 20 patients in treatment arm, 4 did not meet the inclusion criteria of TIMI Flow Grade(TFG) 0/1 and cTFC could not be obtained in 4 patients Of the 20 patients in placebo arm, 4 did not receive the first bolus (drug or placebo) and 3 patients did not meet the inclusion criteria of TFG 0/1. cTFC could not be obtained in 3 patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Treatment | Measurements of Flow Velocity in the Culprit Artery in Terms of Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) | 26 Corrected TIMI Frame Count (cTFC) |
| Placebo Control | Measurements of Flow Velocity in the Culprit Artery in Terms of Corrected Thrombolysis In Myocardial Infarction (TIMI) Frame Count (cTFC) | 14 Corrected TIMI Frame Count (cTFC) |
Secondary
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
Population: Of the 20 patients randomized to the treatment arm, 4 patients did not meet the inclusion criteria of Thrombolysis In Myocardial Infarction (TIMI) Flow Grade(TFG) 0/1.~Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo) and 3 patients did not meet the inclusion criteria of TFG 0/1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | 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 | 7 participants |
| Placebo Control | 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 | 2 participants |
Secondary
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
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
Population: Of the 20 patients in treatment arm, 4 did not meet the inclusion criteria of TIMI Flow Grade(TFG) 0/1 and cTFC could not be obtained in 4 patients Of the 20 patients in placebo arm, 4 did not receive the first bolus (drug or placebo) and 3 patients did not meet the inclusion criteria of TFG 0/1. cTFC could not be obtained in 3 patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | 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 | 1 participants |
| Placebo Control | 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 | 5 participants |
Secondary
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
Thrombolysis In Myocardial Infarction (TIMI) Myocardial Perfusion Grade (TMPG) of 2 or 3 in the territory of the culprit artery
Time frame: Following Primary Percutaneous Coronary Intervention Prior to Second Bolus of the Study Drug
Population: Of the 20 patients randomized to the treatment arm, 4 patients did not meet the inclusion criteria of Thrombolysis In Myocardial Infarction (TIMI) Flow Grade(TFG) 0/1.~Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo) and 3 patients did not meet the inclusion criteria of TFG 0/1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | 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 | 8 participants |
| Placebo Control | 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 | 8 participants |
Secondary
Safety Endpoint: Number of Deaths
Time frame: Through 30days following primary percutaneous coronary intervention
Population: Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Safety Endpoint: Number of Deaths | 1 participants |
| Placebo Control | Safety Endpoint: Number of Deaths | 0 participants |
Secondary
Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias
Time frame: Through 30days following primary percutaneous coronary intervention
Population: Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias | 1 participants |
| Placebo Control | Safety Endpoint: Number of Patients Who Developed Cardiac Arrhythmias | 2 participants |
Secondary
Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding
Time frame: Through 30days following primary percutaneous coronary intervention
Population: Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding | 4 participants |
| Placebo Control | Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minimal Bleeding | 2 participants |
Secondary
Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding
Time frame: Through 30days following PPCI
Population: Of the 20 patients randomized to the placebo arm, 4 patients did not receive the first bolus (drug or placebo)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding | 1 participants |
| Placebo Control | Safety Endpoint: Number of Patients Who Developed Thrombolysis In Myocardial Infarction (TIMI) Minor Bleeding | 0 participants |