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.
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.
Baran
K W
KW
John Nasseff Heart Hospital, St Paul, Minnesota, USA. kbaran@stphc.com
Nguyen
M
M
McKendall
G R
GR
Lambrew
C T
CT
Dykstra
G
G
Palmeri
S T
ST
Gibbons
R J
RJ
Borzak
S
S
Sobel
B E
BE
Gourlay
S G
SG
Rundle
A C
AC
Gibson
C M
CM
Barron
H V
HV
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
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator