The INFUSE - Anterior Myocardial Infarction (AMI) Study

Study Overview
=================
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: Local infusion of abciximab following thrombus aspiration Local infusion of abciximab and no thrombus aspiration No local infusion and thrombus aspiration 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.

Official Title
-----------------
A 2x2 Factorial, Randomized, Multicenter, Single-Blind Evaluation of Intracoronary Abciximab Infusion and Aspiration Thrombectomy in Patients Undergoing Percutaneous Coronary Intervention for Anterior ST-Segment Elevation Myocardial Infarction

Conditions
-----------------
Acute Anterior Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Abciximab local infusion
* Other: No local infusion
* Procedure: Thrombus aspiration


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Local infusion, thrombus aspiration<br>Local infusion of abciximab using the ClearWay™ RX Infusion Catheter following thrombus aspiration. | Drug: Abciximab local infusion<br>* Local infusion of abciximab using the ClearWay™ RX Infusion Catheter<br>Procedure: Thrombus aspiration<br>* Thrombus aspiration<br>|
| Experimental: Local infusion, no aspiration<br>Local infusion of abciximab using the ClearWay™ RX Infusion Catheter and no aspiration | Drug: Abciximab local infusion<br>* Local infusion of abciximab using the ClearWay™ RX Infusion Catheter<br>|
| Active Comparator: No local infusion, thrombus aspiration<br>No local infusion of abciximab, thrombus aspiration. | Other: No local infusion<br>* Intervention without local infusion<br>Procedure: Thrombus aspiration<br>* Thrombus aspiration<br>|
| Active Comparator: No local infusion, no aspiration<br>No local infusion abciximab and no thrombus aspiration | Other: No local infusion<br>* Intervention without local infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 30 Days Post Index Procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 30 Days |