Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

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• 作者：Seizaburo Kashiwagi (1)
  Akira Watanabe (2)
  Hideyuki Ikematsu (3)
  Shinichiro Awamura (4)
  Takako Okamoto (4)
  Mitsutoshi Uemori (5)
  Katsuyasu Ishida (4)
  
• 关键词：Laninamivir ; Neuraminidase inhibitor ; Influenza ; Prophylaxis ; Post ; exposure ; Household contact
• 刊名：Journal of Infection and Chemotherapy
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：19
• 期：4
• 页码：740-749
• 全文大小：237KB
• 参考文献：1. Fox JP, Hall CE, Cooney MK, Foy HM. Influenza virus infections in Seattle families. Am J Epidemiol. 1982;116:212-2.
  2. Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM. Antiviral agents for the treatment and chemoprophylaxis of influenza—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1-4.
  3. Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. 1999;341:1336-3. CrossRef
  4. Kashiwagi S, Kudoh S, Watanabe A, Yoshimura I. Efficacy and safety of the selective oral neuraminidase inhibitor oseltamivir for prophylaxis against influenza–placebo-controlled double-blind multicenter phase III trial. Kansenshogaku Zasshi. 2000;74(12):1062-6.
  5. Welliver R, Mont AS, Carewicz O, Schatteman E, Hassman M, Hedrick J, et al. Effectiveness of oseltamivir in preventing influenza in household contacts. JAMA. 2001;285:748-4. CrossRef
  6. Hayden FG, Belshe R, Villanueva C, Lanno R, Hughes C, Small I, et al. Management of influenza in households: a prospective, randomized, comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis. 2004;189:440-. CrossRef
  7. Monto AS, Robinson DP, Herlocher ML, Hinson JM, Elliott MJ, Crisp A. Zanamivir in the prevention of influenza among healthy adults. JAMA. 1999;282:31-. CrossRef
  8. Hayden FG, Gubareva LV, Monto AS, Klein TC, Elliott MJ, Hammond JM, et al. Inhaled zanamivir for the prevention of influenza in families. N Engl J Med. 2000;343:1282-. CrossRef
  9. Monto AS, Pichichero ME, Blanckenberg ST, Ruuskanen O, Cooper C, Fleming DM, et al. Zanamivir prophylaxis: effective strategy for the prevention of Influenza types A and B within households. J Infect Dis. 2002;186:1582-. CrossRef
  10. Yamashita M, Tomozawa T, Kakuta M, Tokumitsu A, Nasu H, Kubo S. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother. 2009;53:186-2. CrossRef
  11. Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, et al. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009;460:1021-.
  12. Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: a double-blind, randomized, noninferiority clinical trial. Clin Infect Dis. 2010;51:1167-5. CrossRef
  13. Sugaya N, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection. Antimicrob Agents Chemother. 2010;54:2575-2. CrossRef
  14. Watanabe A. A randomized double-blind controlled trial of laninamivir compared with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases. J Infect Chemother. 2013;19:98-02. CrossRef
  15. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Tripartite Guideline: Guideline for Good Clinical Practice. June 1996 (Internet). Cited 2010 March 12. http://www.ich.org/cache/compo/276-254-1.html.
  16. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800-. CrossRef
  17. Ishizuka H, Toyama K, Yoshiba S, Okabe H, Furuie H. Intrapulmonary distribution and pharmacokinetics of laninamivir, a neuraminidase inhibitor, after a single inhaled administration of its prodrug, laninamivir octanoate, in healthy volunteers. Antimicrob Agents Chemother. 2012;56:3873-. CrossRef
  18. Harper SA, Bradley JS, Englund JA, File TM, Graventein S, Hayden FG, et al. Seasonal influenza in adults and children–diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(8):1003-2. CrossRef
  19. Kashiwagi S, Yoshida S, Yamaguchi H, Mitsui N, Tanigawa M, Shiosakai K, et al. Clinical efficacy of long-acting neuraminidase inhibitor laninamivir octanoate hydrate in postmarketing surveillance. J Infect Chemother. 2013;19(2):223-2.
  
• 作者单位：Seizaburo Kashiwagi (1)
  Akira Watanabe (2)
  Hideyuki Ikematsu (3)
  Shinichiro Awamura (4)
  Takako Okamoto (4)
  Mitsutoshi Uemori (5)
  Katsuyasu Ishida (4)
  
  1. Kashiwagi Clinic, SS Building Hakata-Ekimae 4F, 3-21-15 Hakataekimae, Hakata-ku, Fukuoka, 812-0011, Japan
  2. Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Aoba-ku, Sendai, 980-8575, Japan
  3. Department of Clinical Trials, Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan
  4. Clinical Development Department II, Daiichi Sankyo Co., Ltd., Hiromachi 1-2-58, Shinagawa-ku, Tokyo, 140-8710, Japan
  5. Clinical Data and Biostatistics Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan
  

文摘

Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20?mg of laninamivir octanoate once daily for 2?days (LO-2), 20?mg of laninamivir octanoate once daily for 3?days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9?% (19/487) in the LO-2 group, 3.7?% (18/486) in the LO-3 group, and 16.9?% (81/478) in the placebo group (P?<?0.001 for each of the laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0?% [95?% confidence interval (CI) 62.7-5.8] and 78.1?% (95?% CI 64.1-6.7?%) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20?mg of laninamivir octanoate once daily for 2 or 3?days was well tolerated and effectively prevented the development of influenza in household contacts.