title: Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.
abstract: BACKGROUND
  Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent.
  
  
  RESULTS
  The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33).
  
  
  CONCLUSIONS
  RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.
authors.affiliation: John Nasseff Heart Hospital, St Paul, Minnesota, USA. kbaran@stphc.com
authors.forename: K W
authors.initials: KW
authors.lastname: Baran
authors.forename: M
authors.initials: M
authors.lastname: Nguyen
authors.forename: G R
authors.initials: GR
authors.lastname: McKendall
authors.forename: C T
authors.initials: CT
authors.lastname: Lambrew
authors.forename: G
authors.initials: G
authors.lastname: Dykstra
authors.forename: S T
authors.initials: ST
authors.lastname: Palmeri
authors.forename: R J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: S
authors.initials: S
authors.lastname: Borzak
authors.forename: B E
authors.initials: BE
authors.lastname: Sobel
authors.forename: S G
authors.initials: SG
authors.lastname: Gourlay
authors.forename: A C
authors.initials: AC
authors.lastname: Rundle
authors.forename: C M
authors.initials: CM
authors.lastname: Gibson
authors.forename: H V
authors.initials: HV
authors.lastname: Barron
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D018821:CD18 Antigens / Q000276:immunology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator