Clinical trial NCT00976521: The INFUSE - Anterior Myocardial Infarction (AMI) Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Anterior Myocardial Infarction
Lead sponsor: Atrium Medical Corporation
Sponsor class: INDUSTRY
First posted: 2009-09-14
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Primary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Abciximab Infusion vs. No Infusion
timeFrame: 30 Days Post Index Procedure
Secondary outcomes:
measure: Major Secondary Endpoint - Infarct Size at 30 Days as a Percentage of Total Left Ventricular Mass - Aspiration vs. No Aspiration
timeFrame: 30 Days
Other outcomes:
Locations:
city: Takoma Park
country: United States
facility: Washington Adventist Hospital
state: Maryland
city: Charlotte
country: United States
facility: Carolinas Medical Center-SHVI
state: North Carolina
city: Greensboro
country: United States
facility: Moses Cone Vascular Center
state: North Carolina
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Harrisburg
country: United States
facility: Harrisburg Hospital/ Pinnacle Health
state: Pennsylvania
city: Kingsport
country: United States
facility: Wellmont Holston Valley Medical Center
state: Tennessee
city: Virginia Beach
country: United States
facility: Sentara Virginia Beach General Hospital
state: Virginia
city: Braunau
country: Austria
facility: Landeskrankenhaus Braunau/Simbach
city: Bruck/Mur
country: Austria
facility: Landeskrankenhaus Bruck/Mur
city: Graz
country: Austria
facility: Landeskrankenhaus Graz West
city: Innsbruck
country: Austria
facility: Univ. Klinik für Innere Medizin III Innsbruck
city: Vienna
country: Austria
facility: Univ. Klinik für Innere Medizin II
city: Berlin
country: Germany
facility: Charite- University Medicine Campus Benjamin Franklin
city: Darmstadt
country: Germany
facility: Klinikum Villingen Kardiologie
city: Ludwigshafen
country: Germany
facility: Facharzt fur Innere Medizin/Kardiologie
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim - I. Medizinische Klinik
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
city: Ulm
country: Germany
facility: Universtitätsklinikuim Ulm
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
state: NL
city: Eindhoven
country: Netherlands
facility: Catharina Hospital Eindhoven
city: Zwolle
country: Netherlands
facility: Isala Klinieken, Locatie de Weezenlanden
city: Bielsko-Biała
country: Poland
facility: Polsko - Amerykańskie Kliniki Serca II Oddział Kardiologiczny American Heart of Poland Sp. z o.o.
city: Krakow
country: Poland
facility: Krakowskie Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawła II w Krakowie, Centrum Interwencyjne Leczenia Chorób Serca i Naczyń
city: Kraków
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie, Samodzielna Pracownia Hemodynamiki i Angiografii
city: Opole
country: Poland
facility: Pracownia Hemodynamiki Oddziału Kardiologicznego Wojewódzkiego Centrum Medycyny w Opolu
city: Oswiecim
country: Poland
facility: Centrum Kardiologii Inwazyjnej GVM Carint
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie Pracownia Hemodynamiki I Katedry i Kliniki Kardiologii
city: Warszawa
country: Poland
facility: Instytut Kardiologii im. Prymasa Tysiąclecia Kardynała Stefana Wyszyńskiego,I Samodzielna Pracownia Hemodynamiki
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester - Glenfield Hospital
state: U.k.
city: London
country: United Kingdom
facility: King's College Hospital
state: U.k.
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
state: U.k.
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: U.k.
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
state: U.k.
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital, Belfast Trust
city: Bristol
country: United Kingdom
facility: Bristol Heart Institute
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Columbia University
name: Greg W Stone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giustino G, Redfors B, Brener SJ, Kirtane AJ, Genereux P, Maehara A, Dudek D, Neunteufl T, Metzger DC, Crowley A, Mehran R, Gibson CM, Stone GW. Correlates and prognostic impact of new-onset heart failure after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: insights from the INFUSE-AMI trial. Eur Heart J Acute Cardiovasc Care. 2018 Jun;7(4):339-347. doi: 10.1177/2048872617719649. Epub 2017 Aug 22.
citation: Tomey MI, Mehran R, Brener SJ, Maehara A, Witzenbichler B, Dizon JM, El-Omar M, Xu K, Gibson CM, Stone GW. Sex, adverse cardiac events, and infarct size in anterior myocardial infarction: an analysis of intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction (INFUSE-AMI). Am Heart J. 2015 Jan;169(1):86-93. doi: 10.1016/j.ahj.2014.06.019. Epub 2014 Jul 3.
citation: Guerchicoff A, Brener SJ, Maehara A, Witzenbichler B, Fahy M, Xu K, Gersh BJ, Mehran R, Gibson CM, Stone GW. Impact of delay to reperfusion on reperfusion success, infarct size, and clinical outcomes in patients with ST-segment elevation myocardial infarction: the INFUSE-AMI Trial (INFUSE-Anterior Myocardial Infarction). JACC Cardiovasc Interv. 2014 Jul;7(7):733-40. doi: 10.1016/j.jcin.2014.01.166.
citation: Stone GW, Witzenbichler B, Godlewski J, Dambrink JH, Ochala A, Chowdhary S, El-Omar M, Neunteufl T, Metzger DC, Dizon JM, Wolff SD, Brener SJ, Mehran R, Maehara A, Gibson CM. Intralesional abciximab and thrombus aspiration in patients with large anterior myocardial infarction: one-year results from the INFUSE-AMI trial. Circ Cardiovasc Interv. 2013 Oct 1;6(5):527-34. doi: 10.1161/CIRCINTERVENTIONS.113.000644. Epub 2013 Oct 1.
citation: Brener SJ, Maehara A, Dizon JM, Fahy M, Witzenbichler B, Parise H, El-Omar M, Dambrink JH, Mehran R, Oldroyd K, Gibson CM, Stone GW. Relationship between myocardial reperfusion, infarct size, and mortality: the INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction) trial. JACC Cardiovasc Interv. 2013 Jul;6(7):718-24. doi: 10.1016/j.jcin.2013.03.013.
citation: Brener SJ, Witzenbichler B, Maehara A, Dizon J, Fahy M, El-Omar M, Dambrink JH, Genereux P, Mehran R, Oldroyd K, Parise H, Gibson CM, Stone GW. Infarct size and mortality in patients with proximal versus mid left anterior descending artery occlusion: the Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction (INFUSE-AMI) trial. Am Heart J. 2013 Jul;166(1):64-70. doi: 10.1016/j.ahj.2013.03.029. Epub 2013 Apr 30.
citation: Stone GW, Maehara A, Witzenbichler B, Godlewski J, Parise H, Dambrink JH, Ochala A, Carlton TW, Cristea E, Wolff SD, Brener SJ, Chowdhary S, El-Omar M, Neunteufl T, Metzger DC, Karwoski T, Dizon JM, Mehran R, Gibson CM; INFUSE-AMI Investigators. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA. 2012 May 2;307(17):1817-26. doi: 10.1001/jama.2012.421. Epub 2012 Mar 25.
citation: Gibson CM, Maehara A, Lansky AJ, Wohrle J, Stuckey T, Dave R, Cox D, Grines C, Dudek D, Steg G, Parise H, Wolff SD, Cristea E, Stone GW. Rationale and design of the INFUSE-AMI study: A 2 x 2 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. Am Heart J. 2011 Mar;161(3):478-486.e7. doi: 10.1016/j.ahj.2010.10.006. Epub 2011 Jan 28.