title: Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial.
abstract: BACKGROUND
  Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease.
  
  
  METHODS
  We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940.
  
  
  RESULTS
  We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p<0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group.
  
  
  CONCLUSIONS
  Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted.
  
  
  BACKGROUND
  Japanese Ministry of Health, Labour and Welfare.
authors.affiliation: Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan. torukoba@nifty.com
authors.forename: Tohru
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saji
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Otani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Arakawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Kato
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamaoka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Miura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nomura
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fuse
authors.forename: Fukiko
authors.initials: F
authors.lastname: Ichida
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Fukazawa
authors.forename: Chitose
authors.initials: C
authors.lastname: Ogawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Furuno
authors.forename: Hirohide
authors.initials: H
authors.lastname: Tokunaga
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takatsuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Hara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Morikawa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000517:prevention & control*; D003330:Coronary Vessel Anomalies / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies
chemical_list: D000893:Anti-Inflammatory Agents; D007136:Immunoglobulins; D011239:Prednisolone; D001241:Aspirin