Effect of pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to fibrinolysis in acute myocardial infarction: the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) trial.
BACKGROUND
Complement activation mediates myocardial damage that occurs during ischemia and reperfusion through multiple pathways. We performed 2 separate, parallel, double-blind, placebo-controlled trials to determine the effects of pexelizumab (a novel C5 complement monoclonal antibody fragment) on infarct size in patients receiving reperfusion therapy: COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) and COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA). The COMPLY trial is reported here.


RESULTS
Overall, 943 patients with acute ST-segment elevation myocardial infarction (MI) (20% with isolated inferior MI) receiving fibrinolysis were randomly assigned <6 hours after symptom onset to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus plus 0.05 mg/kg per h for 20 hours. Infarct size determined by creatine kinase-MB area under the curve was the primary analysis, which included patients who received at least some study drug and fibrinolysis (n=920). The median infarct size did not differ by treatment (placebo, 5230; bolus, 4952; bolus plus infusion, 5557 [ng/mL] x h; bolus versus placebo, P=0.85; bolus plus infusion versus placebo, P=0.81), nor did the 90-day composite incidence of death, new or worsening congestive heart failure, shock, or stroke (placebo, 18.6%; bolus, 18.4%; bolus plus infusion, 19.7%). Pexelizumab inhibited complement for 4 hours with bolus-only dosing and for 20 to 24 hours with bolus-plus-infusion dosing, with no increase in infections.


CONCLUSIONS
When used adjunctively with fibrinolysis, pexelizumab blocked complement activity but reduced neither infarct size by creatine kinase-MB assessment nor adverse clinical outcomes.
Mahaffey
Kenneth W
KW
Duke Clinical Research Institute, Durham, NC 27715, USA. mahaf002@mc.duke.edu
Granger
Christopher B
CB
Nicolau
Jose C
JC
Ruzyllo
Witold
W
Weaver
W Douglas
WD
Theroux
Pierre
P
Hochman
Judith S
JS
Filloon
Thomas G
TG
Mojcik
Christopher F
CF
Todaro
Thomas G
TG
Armstrong
Paul W
PW
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D017024:Chemotherapy, Adjuvant; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D003402:Creatine Kinase / Q000032:analysis; D052279:Creatine Kinase, MB Form; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy*; D057127:Single-Chain Antibodies; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D005343:Fibrinolytic Agents; D007527:Isoenzymes; D057127:Single-Chain Antibodies; C402724:pexelizumab; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form