INTRO AMI INTEGRILIN AND REDUCED DOSE OF THROMBOLYTIC IN ACUTE MYOCARDIAL INFARCTION
INTRO AMI Study Design
Multi-national, multi-center enrollment
Open-label, dose finding phase
Sequential dose-escalation design
Confirmation phase (planned)
Purpose and Primary Endpoints
To evaluate the incidence of TIMI 3 flow at 60 minutes
To evaluate the incidence of TIMI bleeding during acute hospitalization
Integrilin INTRO AMI
Other Endpoints:
ST segment resolution at 3 hours
TIMI frame count in IRA
TIMI flow at 90 minutes, if available
Integrilin INTRO AMI
Death - cardiovascular or other
Reinfarction
Stroke (CT or MRI documentation)
Hemorrhagic
non-hemorrhagic
Urgent target vessel revascularization
CABG or PTCA, including initial PTCA for TIMI 0-2 flow
Integrilin INTRO AMI Clinical Endpoints
INTRO AMI Study Design
Acute MI <6 hours duration
60 minute angiography
PTCA if clinically indicated
90 minute angiography
Rescue PTCA for TIMI 1-2 flow
Study drug infusion for 72 hours
INTRO AMI Study Design
Heparin 4000 IU IV bolus
800 IU/hr IV infusion
aPTT - 50-70 seconds
ASA 325 mg / day
PCI at discretion of investigator
Integrilin Intro AMI Study Protocol
Integrilin Intro AMI Patient Enrollment
Total Enrolled: 190
Level A (180/1.33) = 35
Level B (180 + 90/1.33) = 37
Level E (180/1.33 + 15/35) = 33
Level F (180 + 90/1.33 +15/35) = 53
Level G (180/2.0 Initial + 15/35) = 32
TIMI Grade 3 Flow at 60 Minutes
33
30
31
30
48
Integrilin bolus 180 180 180 180/90 180/90
Integrilin infusion 1.33 1.33 2.0 1.33 1.33
tPA bolus 25 15 15 25 15
tPA infusion 35 35 35
TIMI Grade 3 Flow at 90 Minutes
33
30
31
30
48
Integrilin bolus 180 180 180 180/90 180/90
Integrilin infusion 1.33 1.33 2.0 1.33 1.33
tPA bolus 25 15 15 25 15
tPA infusion 35 35 35
Bleeding events Site adjudication
Level A (N=35)
Moderate - 2 pts.
Severe - 3 pts.
Level E (N = 33)
Moderate - 5
Severe - 2
Level G (N = 32)
Moderate - 1 pts.
Severe - 0 pts
Level B (N=35)
Moderate - 6 pts.
Severe - 2 pts.
Level F (N = 53)
Moderate - 5
Severe - 0
Preliminary Results - OVERALL TIMI Major Bleeding Events
Single bolus Integrilin
Level A = 3/35
CABG related = 1
Level E = 3/33
CABG related = 1
Level G = 6/32
CABG related = 2
12/100
4 CABG related
Double bolus Integrilin
Level B = 6/35
CABG related = 3
Level F = 7/53
CABG related = 4
13/88
7 CABG related
Efficacy
The combination of Integrilin and reduced dose rt-PA achieves enhanced TIMI 3 flow at 60 and 90 minutes.
Greatest increase in TIMI 3 flow results from a double bolus of Integrilin and with half-dose rt-PA (15/35mg).
Safety
There appears to be a clinically acceptable increase in bleeding related primarily to femoral access site.
Integrilin INTRO AMI Summary and Conclusions
The use of Integrilin in combination with low dose fibrinolytics is a promising therapeutic strategy in acute myocardial infarction.
Large scale clinical-outcome studies will be required to further assess the benefits of this strategy.
Integrilin INTRO AMI Conclusions