1. Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open-Label, Randomized Control Study
- Author
-
Hidetoshi Takada, Junji Kishimoto, Takuro Ohno, Yasuhiko Takahashi, Shouichi Ohga, Takuya Hara, Hideki Nakayama, Yasuhiro Onoe, Kenji Furuno, Kenichiro Yamamura, Hisanori Nishio, Takayuki Shimose, Toshiro Hara, Kenjiro Saigo, Ken Hatae, Tatsuo Harada, Noriko Ohbuchi, Hironori Yamashita, Yumi Mizuno, Etsuro Nanishi, Mitsuharu Fukazawa, and Ryo Kadoya
- Subjects
Male ,Time Factors ,Gastroenterology ,Pediatrics ,biofilm ,law.invention ,Pathogenesis ,0302 clinical medicine ,Intravenous Immunoglobulin Therapy ,Randomized controlled trial ,Japan ,law ,Recurrence ,Clarithromycin ,hemic and lymphatic diseases ,Pediatric Cardiology ,Clinical Studies ,030212 general & internal medicine ,Child ,Original Research ,relapse ,Immunoglobulins, Intravenous ,clinical trial ,Anti-Bacterial Agents ,Treatment Outcome ,Child, Preschool ,Drug Therapy, Combination ,Female ,Open label ,Cardiology and Cardiovascular Medicine ,medicine.drug ,medicine.medical_specialty ,Adolescent ,Mucocutaneous Lymph Node Syndrome ,03 medical and health sciences ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Bacteriological Techniques ,Innate immune system ,Kawasaki disease ,business.industry ,Infant ,Length of Stay ,medicine.disease ,Immunity, Innate ,Clinical trial ,pediatric ,Biofilms ,Immunology ,business ,Multiplex Polymerase Chain Reaction - Abstract
Background We 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 Results We 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). Conclusions Although 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 Registration URL: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000015437.
- Published
- 2017