Acute Anterior Myocardial Infarction
Conditions
Brief summary
This is a multicenter, open-label, controlled, single-blind, randomized study with up to 452 subjects enrolled in up to 50 US and European sites. Subjects who present with anterior ST-elevation myocardial infarction (STEMI) and an occluded proximal or mid left anterior descending (LAD) with TIMI 0/1/2 flow will be eligible for randomization to one of the following arms: 1. Local infusion of abciximab following thrombus aspiration 2. Local infusion of abciximab and no thrombus aspiration 3. No local infusion and thrombus aspiration 4. No local infusion and no thrombus aspiration In addition, a cardiac magnetic resonance imaging (MRI) sub-study evaluating microvascular obstruction (MVO) will be performed with up to 160 subjects at up to 20 sites.
Detailed description
The primary objective of the study is to demonstrate that among subjects undergoing primary PCI for anterior STEMI treated with a bivalirudin monotherapy anticoagulation strategy, the intracoronary infusion of an abciximab bolus with or without thrombus aspiration prior to stent implantation, compared to no infusion with or without thrombus aspiration (standard of care), results in 1) reduced infarct size measured by cardiac MRI at 30 days (range -7 days/+14 days; i.e., between 23 and 44 days), 2) reduce microvascular obstruction (MVO) by cardiac MRI at 5 + 2 days (i.e., between 3 and 7 days), 3) enhanced ST-segment resolution, 4) improved myocardial perfusion, 5) reduced thrombus burden and angiographic complications, and 6) no increase in major and minor bleeding.
Interventions
DRUGAbciximab local infusion
Local infusion of abciximab using the ClearWay™ RX Infusion Catheter
OTHERNo local infusion
Intervention without local infusion
PROCEDUREThrombus aspiration
Thrombus aspiration
Sponsors
Atrium Medical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * The subject must be \>18 years of age; * Subject is experiencing clinical symptoms consistent with AMI (e.g., chest pain, arm pain, etc.,) \>30 minutes duration and unresponsive to nitroglycerin; * Anterior MI with ECG showing at least 1 mm of ST-segment elevation in 2 or more contiguous leads in V1-V4, or new (or presumably new) left bundle branch block; * Anticipated symptom onset to balloon or aspiration time of ≤5 hours; * The subject and his/her physician are willing to comply with specified follow-up evaluations; * The subject or legally authorized representative has been informed of the nature of the study, agrees to its provisions and has been provided and signed written informed consent, approved by the appropriate Medical Ethics Committee (MEC) or Institutional Review Board (IRB) * Infarct artery located in the proximal or mid left anterior descending coronary artery, with TIMI 0/1/2 flow at the time of initial diagnostic angiography (prior to wire passage); * Based on coronary anatomy, PCI is indicated for revascularization; * Only one epicardial coronary artery will be treated; * Expected ability to deliver a ClearWay™ RX Infusion Catheter to the infarct lesion (absence of excessive tortuosity, diffuse disease or moderate/heavy calcification). Key
Exclusion criteria
* Prior myocardial infarction, or known prior systolic dysfunction (known ejection fraction \<40% by any prior measure or regional wall motion abnormalities); * An elective surgical procedure is planned that would necessitate interruption of anti-platelet agents during the first twelve months post enrollment; * Subjects who previously underwent coronary stent implantation and in whom coronary angiography demonstrates stent thrombosis to be the cause of the AMI; * Subject has previously undergone an angioplasty or stenting procedure in the left anterior descending artery; * Definite planned use of aspiration, atherectomy, thrombectomy and/or distal protection catheters prior to PTCA or stent implantation (other than in subjects randomized to thrombus aspiration); * Any contraindication to undergo MRI imaging. * Multivessel intervention required during the index procedure (subjects may be enrolled if treatment of more than one lesion in the LAD or its branches is required, however) (planned staged procedures are permitted with strong recommendation to be performed after 30-day clinical and MRI endpoints are completed); * Severe vessel tortuosity, diffuse disease or severe calcification is present which may impede successful delivery of the ClearWay™ RX Infusion Catheter or the Export® Aspiration Catheter; * Features are present highly unfavorable for PCI; * Target lesion is present within a bypass graft conduit; * MI is due to thrombosis within or adjacent to a previously implanted stent; * Left ventriculography demonstrates severe mitral regurgitation or a VSD; * Unprotected left main stenosis \>40% or that will require intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Abciximab Infusion vs. No Infusion | 30 Days Post Index Procedure | The primary endpoint of the INFUSE AMI study is infarct size as a percentage of total left ventricular mass at 30 days as measured by cardiac MRI (cMRI), comparing the pooled randomized active (abciximab) infusion to the pooled non infusion arms, without regard to aspiration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Secondary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Aspiration vs. No Aspiration | 30 Days | The major secondary endpoint of the INFUSE AMI Study is infarct size as a percentage of total myocardial mass at 30 days measured by cardiac MRI (cMRI), comparing the pooled randomized aspiration arms to the pooled no aspiration arms, without regard to abciximab infusion. |
Countries
Austria, Germany, Netherlands, Poland, United Kingdom, United States
Participant flow
Recruitment details
Between 28-Nov-09 and 02-Dec-11, 452 subjects meeting all clinical eligibility criteria were consented and enrolled at 37 US and European sites.
Pre-assignment details
Subjects were randomized in a 1:1:1:1 ratio to each of the randomized groups (abciximab infusion with aspiration, abciximab infusion without aspiration, no infusion with aspiration, no infusion without aspiration).
Participants by arm
| Arm | Count |
|---|---|
| Local Infusion, Thrombus Aspiration Local infusion of abciximab using the ClearWay™ RX Infusion Catheter following thrombus aspiration. | 118 |
| Local Infusion, no Aspiration Local infusion of abciximab using the ClearWay™ RX Infusion Catheter and no thrombus aspiration | 111 |
| No Local Infusion, Thrombus Aspiration No local infusion of abciximab, thrombus aspiration. | 111 |
| No Local Infusion, no Aspiration No local infusion of abciximab and no thrombus aspiration | 112 |
| Total | 452 |
Baseline characteristics
| Characteristic | Local Infusion, Thrombus Aspiration | Local Infusion, no Aspiration | No Local Infusion, Thrombus Aspiration | No Local Infusion, no Aspiration | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 32 Participants | 50 Participants | 45 Participants | 165 Participants |
| Age, Categorical Between 18 and 65 years | 80 Participants | 79 Participants | 61 Participants | 67 Participants | 287 Participants |
| Age Continuous | 60.0 years | 56.0 years | 62.0 years | 62.5 years | 61.0 years |
| Region of Enrollment Austria | 13 participants | 14 participants | 11 participants | 9 participants | 47 participants |
| Region of Enrollment Germany | 22 participants | 21 participants | 19 participants | 19 participants | 81 participants |
| Region of Enrollment Netherlands | 14 participants | 11 participants | 10 participants | 15 participants | 50 participants |
| Region of Enrollment Poland | 25 participants | 24 participants | 27 participants | 23 participants | 99 participants |
| Region of Enrollment United Kingdom | 30 participants | 26 participants | 32 participants | 34 participants | 122 participants |
| Region of Enrollment United States | 14 participants | 15 participants | 12 participants | 12 participants | 53 participants |
| Sex: Female, Male Female | 34 Participants | 27 Participants | 26 Participants | 31 Participants | 118 Participants |
| Sex: Female, Male Male | 84 Participants | 84 Participants | 85 Participants | 81 Participants | 334 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 31 / 118 | 31 / 111 | 35 / 111 | 41 / 112 |
Outcome results
Primary
Primary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Abciximab Infusion vs. No Infusion
The primary endpoint of the INFUSE AMI study is infarct size as a percentage of total left ventricular mass at 30 days as measured by cardiac MRI (cMRI), comparing the pooled randomized active (abciximab) infusion to the pooled non infusion arms, without regard to aspiration.
Time frame: 30 Days Post Index Procedure
Population: Evaluable cardiac MRI (cMRI) results at 30 days to assess percentage of total left ventricular mass were available for 181 and 172 patients randomized to intracoronary abciximab infusion versus no abciximab infusion, respectively for the ITT (intention to treat) analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abciximab Infusion | Primary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Abciximab Infusion vs. No Infusion | 15.1 Percentage of Left Ventricular Mass |
| No Infusion | Primary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Abciximab Infusion vs. No Infusion | 17.9 Percentage of Left Ventricular Mass |
| Combined | Primary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Abciximab Infusion vs. No Infusion | 17.2 Percentage of Left Ventricular Mass |
Comparison: The primary endpoint of infarct size at 30 days measured by cardiac MRI, was summarized using the median, IQR, minimum and maximum values, in each infusion group, comparing the pooled active infusion arm to the pooled control non-infusion arm with the Wilcoxon rank sum test in the ITT analysis set. Data was only analyzed in subjects completing the cardiac MRI study and for whom the imaging data was received and deemed analyzable by the core laboratory.p-value: 0.034Wilcoxon (Mann-Whitney)
Secondary
Major Secondary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Aspiration vs. No Aspiration
The major secondary endpoint of the INFUSE AMI Study is infarct size as a percentage of total myocardial mass at 30 days measured by cardiac MRI (cMRI), comparing the pooled randomized aspiration arms to the pooled no aspiration arms, without regard to abciximab infusion.
Time frame: 30 Days
Population: Evaluable cardiac MRI (cMRI) results at 30 days to assess percentage of total myocardial mass were available for 192 and 190 patients randomized to thrombus aspiration versus no no thrombus aspiration, respectively for the ITT (intention to treat) analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abciximab Infusion | Major Secondary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Aspiration vs. No Aspiration | 17.0 Percentage of Total Myocardial Mass |
| No Infusion | Major Secondary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Aspiration vs. No Aspiration | 17.3 Percentage of Total Myocardial Mass |
| Combined | Major Secondary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Aspiration vs. No Aspiration | 17.2 Percentage of Total Myocardial Mass |
Comparison: The primary endpoint of infarct size at 30 days measured by cardiac MRI, was summarized using the median, IQR, minimum and maximum values, in each infusion group, comparing the pooled active infusion arm to the pooled control non-infusion arm with the Wilcoxon rank sum test in the ITT analysis set. Data was only analyzed in subjects completing the cardiac MRI study and for whom the imaging data was received and deemed analyzable by the core laboratory.p-value: 0.51Wilcoxon (Mann-Whitney)