title: An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study).
abstract: Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion injury. Inflammatory mediators released from potentially viable myocytes cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutrophil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit infarct size and preserve left ventricular function. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We found no clinically significant differences in vital signs, physical examination, laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myocardial single-photon emission computed tomographic imaging 120 to 260 hours after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse events, including infections. Thus, Hu23F2G appears safe and well tolerated in patients undergoing PTCA for AMI.
authors.affiliation: Mayo Physician Alliance for Clinical Trials, Rochester, Minnesota 55902, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rusnak
authors.forename: S L
authors.initials: SL
authors.lastname: Kopecky
authors.forename: I P
authors.initials: IP
authors.lastname: Clements
authors.forename: R J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: A E
authors.initials: AE
authors.lastname: Holland
authors.forename: H S
authors.initials: HS
authors.lastname: Peterman
authors.forename: J S
authors.initials: JS
authors.lastname: Martin
authors.forename: J B
authors.initials: JB
authors.lastname: Saoud
authors.forename: R L
authors.initials: RL
authors.lastname: Feldman
authors.forename: W M
authors.initials: WM
authors.lastname: Breisblatt
authors.forename: M
authors.initials: M
authors.lastname: Simons
authors.forename: C J
authors.initials: CJ
authors.lastname: Gessler
authors.forename: A S
authors.initials: AS
authors.lastname: Yu
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D016009:Chi-Square Distribution; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010865:Pilot Projects; D011336:Probability; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018696:Neuroprotective Agents; C115464:rovelizumab