title: A randomized trial of icatibant in ACE-inhibitor-induced angioedema.
abstract: BACKGROUND
  Angioedema induced by treatment with angiotensin-converting-enzyme (ACE) inhibitors accounts for one third of angioedema cases in the emergency room; it is usually manifested in the upper airway and the head and neck region. There is no approved treatment for this potentially life-threatening condition.
  
  
  METHODS
  In this multicenter, double-blind, double-dummy, randomized phase 2 study, we assigned patients who had ACE-inhibitor-induced angioedema of the upper aerodigestive tract to treatment with 30 mg of subcutaneous icatibant, a selective bradykinin B2 receptor antagonist, or to the current off-label standard therapy consisting of intravenous prednisolone (500 mg) plus clemastine (2 mg). The primary efficacy end point was the median time to complete resolution of edema.
  
  
  RESULTS
  All 27 patients in the per-protocol population had complete resolution of edema. The median time to complete resolution was 8.0 hours (interquartile range, 3.0 to 16.0) with icatibant as compared with 27.1 hours (interquartile range, 20.3 to 48.0) with standard therapy (P=0.002). Three patients receiving standard therapy required rescue intervention with icatibant and prednisolone; 1 patient required tracheotomy. Significantly more patients in the icatibant group than in the standard-therapy group had complete resolution of edema within 4 hours after treatment (5 of 13 vs. 0 of 14, P=0.02). The median time to the onset of symptom relief (according to a composite investigator-assessed symptom score) was significantly shorter with icatibant than with standard therapy (2.0 hours vs. 11.7 hours, P=0.03). The results were similar when patient-assessed symptom scores were used.
  
  
  CONCLUSIONS
  Among patients with ACE-inhibitor-induced angioedema, the time to complete resolution of edema was significantly shorter with icatibant than with combination therapy with a glucocorticoid and an antihistamine. (Funded by Shire and the Federal Ministry of Education and Research of Germany; ClinicalTrials.gov number, NCT01154361.).
authors: From the Department of Otorhinolaryngology (M.B., U.S.), Münchner Studienzentrum (B.S.), and Institut für Medizinische Statistik und Epidemiologie (A.H., V.K.), Klinikum rechts der Isar, Technische Universität München, and the Department of Otorhinolaryngology, Grosshadern Medical Center of the University of Munich (K.S., M.H.), Munich, the Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm ( J.G., N.R., J.V., T.K.H), and the Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf, Düsseldorf (G.K.) - all in Germany.
authors: Murat
authors: M
authors: Baş
authors: Jens
authors: J
authors: Greve
authors: Klaus
authors: K
authors: Stelter
authors: Miriam
authors: M
authors: Havel
authors: Ulrich
authors: U
authors: Strassen
authors: Nicole
authors: N
authors: Rotter
authors: Johannes
authors: J
authors: Veit
authors: Beate
authors: B
authors: Schossow
authors: Alexander
authors: A
authors: Hapfelmeier
authors: Victoria
authors: V
authors: Kehl
authors: Georg
authors: G
authors: Kojda
authors: Thomas K
authors: TK
authors: Hoffmann
mesh_terms: D000368:Aged; D000799:Angioedema / Q000139:chemically induced / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D001920:Bradykinin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D002974:Clemastine / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065094:Bradykinin B2 Receptor Antagonists; D005938:Glucocorticoids; D006634:Histamine H1 Antagonists; C065679:icatibant; D002974:Clemastine; D011239:Prednisolone; D001920:Bradykinin