Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Jul 2017)

Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open‐Label, Randomized Control Study

  • Etsuro Nanishi,
  • Hisanori Nishio,
  • Hidetoshi Takada,
  • Kenichiro Yamamura,
  • Mitsuharu Fukazawa,
  • Kenji Furuno,
  • Yumi Mizuno,
  • Kenjiro Saigo,
  • Ryo Kadoya,
  • Noriko Ohbuchi,
  • Yasuhiro Onoe,
  • Hironori Yamashita,
  • Hideki Nakayama,
  • Takuya Hara,
  • Takuro Ohno,
  • Yasuhiko Takahashi,
  • Ken Hatae,
  • Tatsuo Harada,
  • Takayuki Shimose,
  • Junji Kishimoto,
  • Shouichi Ohga,
  • Toshiro Hara

DOI
https://doi.org/10.1161/JAHA.116.005370
Journal volume & issue
Vol. 6, no. 7

Abstract

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BackgroundWe previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. Methods and ResultsWe conducted an open‐label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty‐one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [P=0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P=0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P=0.049). ConclusionsAlthough IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. Clinical Trial RegistrationURL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437.

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