Immune deficiencies, infection, and systemic immune disordersEfficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks
Section snippets
Study design
This multinational, parallel-group, randomized, placebo-controlled, 3-arm, double-blind, phase II/III study (with a dose-finding substudy) was conducted between August 2005 and December 2007. Our aim was to show that C1-INH shortens the time to onset of symptom relief in acute abdominal or facial HAE attacks compared with placebo and to provide a statistically secure dosing recommendation for C1-INH.
The independent ethics committee or institutional review board at each participating center
Study population
We randomized 125 patients at 36 centers worldwide to receive double-blind treatment, of whom 42 were assigned to receive placebo, 40 to receive C1-INH 10 U/kg, and 43 to receive C1-INH 20 U/kg (Fig 1).
The treatment groups were similar in terms of sex, age, and race or ethnic group (Table I). Most patients (87.1%) had type 1 HAE. Danazol was taken during the study by 14 (11.3%) patients. Overall, 98 (79.0%) patients experienced abdominal attacks, and 25 (20.2%) experienced facial attacks. One
Discussion
C1 esterase inhibitor concentrate has been in clinical use for treating acute type I and II HAE attacks since 1979. Most information on this use is based on observational studies, which have consistently reported beneficial efficacy and safety of C1-INH when treating acute HAE attacks in adults and children.29, 30, 31, 32, 33, 34 None of these studies had a randomized, placebo-controlled design to evaluate the most suitable dose of C1-INH. To address this issue, we conducted a double-blind,
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T.J.C., R.J.L., R.L.W., A.K.B., D.H., K.O., A.R., B.R., D.M., T.S., V.G.-P., and J.A.B. received research support as investigators in this study sponsored by CSL Behring.
Disclosure of potential conflict of interest: T. J. Craig has served as a consultant for and has received research support from Dyax, CSL Behring, Pharming, Jerini, and ViroPharma/Lev and is a board member of the American College of Allergy, Asthma & Immunology and a nominee for an Interest Section at the American Academy of Allergy, Asthma & Immunology. R. J. Levy has served as a consultant for CSL Behring, Alain, Sepracor, Dyax, and Jerini and has received research support from Grifols, CSL Behring, Pharming, Lev, Dyax Corp, AstraZeneca, Sanofi-Aventis, and Talecris. R. L. Wasserman has served as a consultant for CSL Behring. A. K. Bewtra has received research support from CSL Behring, Pfizer, Merck, and the National Institutes of Health. D. Hurewitz has served as a consultant for CSL Behring and has received research support from CSL Behring and Lev. A. Reshef has received lecture honoraria from Jerini, Germany, and CSL Behring, Germany, and has received research support from CSL Behring, Germany, Pharming, The Netherlands, and Jerini, Germany. B. Ritchie has received research support from CSL Behring and is a committee member of the Canadian Immunodeficiency Patient Organization, Medical and Scientific Advisory Committees. P. C. Kiessling is employed by CSL Behring. H.-O. Keinecke has served as a consultant for CSL Behring. J. A. Bernstein has received research support from Dyax, CSL Behring, Pharming, Jerini, and Lev. The rest of the authors have declared that they have no conflict of interest.