title: Effectiveness of ecallantide in treating angiotensin-converting enzyme inhibitor-induced angioedema in the emergency department.
abstract: BACKGROUND
  Angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-AE) is mediated by bradykinin. There remains an unmet treatment need because these patients, when presenting to the emergency department (ED), do not respond to conventional therapies, such as antihistamines and corticosteroids.
  
  
  OBJECTIVE
  To estimate the treatment effect of ecallantide, a recombinant plasma kallikrein inhibitor, in ED patients with ACEI-AE in whom conventional therapy fails.
  
  
  METHODS
  This was a triple-blind (patient, physician, and statistician), randomized, controlled, phase 2 study to estimate the magnitude of safety and efficacy signals for designing a definitive phase 3 trial comparing conventional therapy with ecallantide to conventional therapy with placebo. Patients were enrolled from April 1, 2010, through January 31, 2013. The primary efficacy study end point was achieving discharge criteria from the ED within 4 hours after initiating study-related treatment.
  
  
  RESULTS
  Discharge criteria from the ED was met in 4 hours or less for 8 (31%) of 26 patients receiving ecallantide vs 5 of (21%) 24 patients receiving placebo (difference in proportions, 10%; 95% confidence interval, -14% to 34%). Ecallantide was well tolerated in both groups.
  
  
  CONCLUSIONS
  The results from this preliminary study reveal that ecallantide is safe to use and may increase the proportion of patients who meet early discharge criteria by approximately10%. A larger phase 3 study is necessary to confirm the efficacy and evaluate the cost-effectiveness of ecallantide use for ACEI-AE in the ED setting.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01036659.
authors.affiliation: Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: Jonathan.Bernstein@uc.edu.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.affiliation: Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Moellman
authors.affiliation: Department of Emergency Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Collins
authors.affiliation: Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Kimberly W
authors.initials: KW
authors.lastname: Hart
authors.affiliation: Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Lindsell
mesh_terms: D000799:Angioedema / Q000139:chemically induced / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D001920:Bradykinin / Q000096:biosynthesis; D004311:Double-Blind Method; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos / Q000008:administration & dosage
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; D010919:Placebos; C511194:ecallantide; D007610:Kallikreins; D001920:Bradykinin