title: Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial.
abstract: OBJECTIVE
  We compare the safety and efficacy of ecallantide with placebo in subjects undergoing assessment for acute angiotensin-converting enzyme inhibitor-induced angioedema (ACEIA) in an emergency department (ED).
  
  
  METHODS
  This was a multicenter, phase 2, double-blind study with subjects randomized to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo plus physician-directed conventional therapy. The primary endpoint was defined as meeting predetermined discharge eligibility criteria within 6 hours of study drug administration. Discharge criteria included improvement of edema, stable vital signs, absence of stridor, absence of dyspnea or use of accessory muscles during respiration, absence of drooling, and ability to drink without difficulty.
  
  
  RESULTS
  An interim analysis showed that a high percentage of subjects met the primary endpoint, and the study was halted. Overall, 79 subjects were randomized and 76 had data for analysis. Most had mild (45%) or moderate (42%) ACEIA. The discharge eligibility endpoint was met by 72% of the placebo group and 85%, 89%, and 89% of the ecallantide 10-, 30-, and 60-mg groups, respectively. This difference in meeting discharge eligibility endpoint criteria between treatment groups was not statistically significant. The incidence of treatment-emergent adverse events was similar between placebo and active-treatment groups.
  
  
  CONCLUSIONS
  The addition of ecallantide to standard therapy does not appear to improve angioedema compared with placebo in ED patients with ACEIA. Our data suggest that most ED patients presenting with mild to moderate ACEIA are likely to meet our discharge eligibility criteria within 6 hours of treatment, regardless of intervention. Further studies to assess the utility of ecallantide in patients with more severe angioedema may be useful. No new safety signals related to ecallantide administration were identified.
authors.affiliation: Washington University School of Medicine, St. Louis, MO. Electronic address: lewisl@wusm.wustl.edu.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Lewis
authors.affiliation: Eastern Virginia Medical School, Norfolk, VA.
authors.forename: Charles
authors.initials: C
authors.lastname: Graffeo
authors.affiliation: DeKalb Medical Center, Decatur, GA.
authors.forename: Pascal
authors.initials: P
authors.lastname: Crosley
authors.affiliation: Henry Ford Health System, Detroit, MI.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Klausner
authors.affiliation: William Beaumont Hospital, Royal Oak, MI.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Clark
authors.affiliation: East Carolina University, Greenville, NC.
authors.forename: Anthony
authors.initials: A
authors.lastname: Frank
authors.affiliation: Hennepin County Medical Center, Minneapolis, MN.
authors.forename: James
authors.initials: J
authors.lastname: Miner
authors.affiliation: Dyax Corp, Burlington, MA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Iarrobino
authors.affiliation: Dyax Corp, Burlington, MA.
authors.forename: Yung
authors.initials: Y
authors.lastname: Chyung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000799:Angioedema / Q000139:chemically induced / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; C511194:ecallantide; D007610:Kallikreins