Kobayashi 2012.

Methods	Multicentre (74 hospitals in Japan), prospective, randomised, blinded end points 29 September 2008 to 2 December 2010
Participants	Eligible participants had a diagnosis of KD (Japanese diagnostic guidelines) and a risk score of 5 points or higher, which emphasised the positive predictive value of no response to initial treatment with IVIG (2 points for each of the following: blood sodium < 133, < 4 days of fever at diagnosis, AST > 100, neutrophils > 80% of total WCC; 1 point for each of the following: platelet count < 30 x 104, CRP > 100, age < 12 months) Excluded were children with a history of KD, those diagnosed on or after day 9 of fever, those with coronary artery abnormalities prior to enrolment, those who were afebrile prior to enrolment, those who had received steroids in the previous 30 days before the study, those who had received IVIG in the previous 180 days before the study, those with concomitant severe medical disorders, or those with suspected infectious disease 2014 children assessed for eligibility. 1547 did not meet inclusion criteria (1436 had low risk scores, 44 had previous diagnosis of KD, 24 had defervescence, 16 had suspected infectious disease, 12 had presence of coronary artery abnormality at diagnosis, 10 had illness for > 9 days, 3 had pre‐existing severe disease, 1 had a history of IVIG use, 1 had history of steroid use, 219 declined to participate. 248 participants randomly assigned. Steroid group: 125 (4 excluded: 1 withdrew consent, 2 had presence of coronary artery abnormality, 1 had misdiagnosis of KD) Control group: 123 (2 excluded: 1 had presence of coronary artery abnormalities at enrolment, 1 did not receive IVIG) No significant differences between groups at baseline
Interventions	Control: IVIG 2 g/kg over 24 h Aspirin 30 mg/kg/day until afebrile, then 3 to 5 mg/kg/day for at least 28 days from fever onset Steroid group: IVIG 2 g/kg over 24 h Aspirin 30 mg/kg/day until afebrile, then 3 to 5 mg/kg/day for at least 28 days from fever onset IV prednisolone 2 mg/kg/day in 3 divided doses for 5 days, or until fever resolved, if longer. When CRP normalised (< 5mg/L) prednisolone doses were tapered in 5 day steps over 15 days, from 2 mg/kg/day, to 1 mg/kg/day to 0.5 mg/kg/day 0.5 mg/kg/day H2 blocker famotidine whilst on prednisolone
Outcomes	Primary end point: Detection of coronary artery abnormality during study period (luminal diameter > 3.0 mm in a child < 5 years, or > 4.0 mm in a child > 5 yrs, when the internal diameter of a segment was at least 1.5 times that of an adjacent segment, or when a luminal contour was clearly irregular) Secondary end point: Incidence of coronary artery abnormality at week 4 after enrolment Incidence of need for additional rescue treatment CRP concentrations at 1 and 2 weeks after enrolment Incidence of serious adverse events
Notes	Funding source: Japanese Ministry of Health, Labour and Welfare – had no role in study design, data collection, data analysis, data interpretation or writing of the report RASIE study. Registered with University Hospital Medical Information Network clinical trials registry, number UMIN000000940 Pre‐planned interim analysis after enrolment of the 200th participant in June 2010 demonstrated significance difference in the incidence of coronary artery abnormalities between the 2 treatment groups (P < 0.0001), therefore independent data and safety monitoring committee recommended termination of the study. Study terminated on 2 December 2010
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Computer generated randomisation sequence" Comment: likely adequate and performed
Allocation concealment (selection bias)	Low risk	Quote: "Centrally maintained table of random numbers" Comment: likely adequate
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "Participant and treating physician non‐blinded" Comment: unclear how this would have influenced results
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Blinded end point" Echocardiography assessors blinded Comment: appears adequate
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Intention to treat analysis used" Comment: appears adequate
Selective reporting (reporting bias)	Low risk	Published methodology consistent with that reported in published results
Other bias	Low risk	None identified