title: Study protocol for a phase III multicentre, randomised, open-label, blinded-end point trial to evaluate the efficacy and safety of immunoglobulin plus cyclosporin A in patients with severe Kawasaki disease (KAICA Trial).
abstract: BACKGROUND
  Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca(2+)/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD.
  
  
  METHODS
  This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment.
  
  
  BACKGROUND
  The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations.
  
  
  BACKGROUND
  JMA-IIA00174; Pre-results.
authors.affiliation: Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Aoyagi
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Onouchi
authors.affiliation: Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Ebata
authors.affiliation: Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
authors.forename: Kengo
authors.identifier: http://orcid.org/0000-0003-4529-9045
authors.initials: K
authors.lastname: Nagashima
authors.affiliation: Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Terauchi
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Terai
authors.affiliation: Clinical Research Centre, Chiba University Hospital, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hanaoka
authors.affiliation: Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D007223:Infant; D007564:Japan; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D016016:Proportional Hazards Models; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D016756:Immunoglobulins, Intravenous; D016572:Cyclosporine; D001241:Aspirin
keywords: CLINICAL PHARMACOLOGY