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Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema

Cicardi, M.; Banerji, A.; Bracho, F.; Malbran, A.; Rosenkranz, B.; Riedl, M.; Bork, K.; Lumry, W.; Aberer, W. and Bier, H., et al. (2010) In New England Journal of Medicine 363(6). p.532-541
Abstract
BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to... (More)
BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.) (Less)
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New England Journal of Medicine
volume
363
issue
6
pages
532 - 541
publisher
Massachusetts Medical Society
external identifiers
  • wos:000280552700007
  • scopus:77955295556
ISSN
0028-4793
DOI
10.1056/NEJMoa0906393
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English
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c47411d8-02ff-4eb4-8169-1470cf8f6fa4 (old id 1677818)
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2010-09-21 10:42:16
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2018-07-15 03:02:07
@article{c47411d8-02ff-4eb4-8169-1470cf8f6fa4,
  abstract     = {BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P&lt;0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)},
  author       = {Cicardi, M. and Banerji, A. and Bracho, F. and Malbran, A. and Rosenkranz, B. and Riedl, M. and Bork, K. and Lumry, W. and Aberer, W. and Bier, H. and Bas, M. and Greve, J. and Hoffmann, T. K. and Farkas, H. and Reshef, A. and Ritchie, B. and Yang, W. and Grabbe, J. and Kivity, S. and Kreuz, W. and Levy, R. J. and Luger, T. and Obtulowicz, K. and Schmid-Grendelmeier, P. and Bull, C. and Sitkauskiene, B. and Smith, W. B. and Toubi, E. and Werner, Sonja and Anne, S. and Bjorkander, J. and Bouillet, L. and Cillari, E. and Hurewitz, D. and Jacobson, K. W. and Katelaris, C. H. and Maurer, M. and Merk, H. and Bernstein, J. A. and Feighery, C. and Floccard, B. and Gleich, G. and Hebert, J. and Kaatz, M. and Keith, P. and Kirkpatrick, C. H. and Langton, D. and Martin, L. and Pichler, C. and Resnick, D. and Wombolt, D. and Fernandez Romero, D. S. and Zanichelli, A. and Arcoleo, F. and Knolle, J. and Kravec, I. and Dong, L. and Zimmermann, J. and Rosen, K. and Fan, W. -T.},
  issn         = {0028-4793},
  language     = {eng},
  number       = {6},
  pages        = {532--541},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema},
  url          = {http://dx.doi.org/10.1056/NEJMoa0906393},
  volume       = {363},
  year         = {2010},
}