Newburger 2007.

Methods	Multicentre (8 centres in North America), randomised, double‐blind, placebo‐controlled trial. December 2002 to December 2004
Participants	All participants between day 4 and day 10 of illness Inclusion criteria: Child met > 4 of principal clinical criteria. Coronary artery z‐score of > 2.5 (RCA or LAD) and met 2 principal clinical criteria if < 6 months, 3 criteria if > 6 months Presence of a coronary artery aneurysm and met at least 1 clinical criterion Exclusion criteria: Previous treatment with IVIG Oral steroid use in preceding 2 weeks Presence of a disease known to mimic KD Contraindications to steroid use Allergy to aspirin 589 children identified. 276 were ineligible (185 met at least 1 exclusion criterion. 95 did not meet inclusion criteria) 313 considered eligible, of these 199 parents granted consent 199 children randomised Treatment: 101 participants Control: 98 participants No significant differences between groups at baseline randomisation
Interventions	Control: 1 mg/kg diphenhydramine IVIG 2 g/kg over 10 h Aspirin 80 to 100 mg/kg/day until they were afebrile for 48 h, then 3 to 5 mg/kg/day aspirin until study completion Treatment: One‐off dose of 30mg/kg intravenous methyl prednisolone 1 mg/kg diphenhydramine IVIG 2 g/kg over 10 h Aspirin 80 to 100 mg/kg/day until they were afebrile for 48 h, then 3 to 5 mg/kg/day aspirin until study completion If children had recurrent fever > 36 h after the initial infusion (and no alternative source was found) then a further dose of IVIG 2 mg/kg, then if they remained pyrexial after a further 36 h another dose of IVIG 2 mg/kg was administered
Outcomes	Primary outcome: Detection of coronary artery abnormality during study period (luminal diameter > 3.0 mm in a child < 5 yrs, 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, of a z‐score of > 2.5) Secondary outcomes: Duration of fever Number of days spent in hospital until first discharge Number of total days spent in hospital during study period Number of episodes of re‐treatment with IVIG Incidence of adverse events Laboratory data at week 1 and 5 after randomisation
Notes	ClinicalTrials.gov number: NCT00132080 Funding: National Institutes of Health and Higgins Family Cardiology Research Fund No relevant potential conflict of interest reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Randomly assigned" with use of "dynamic balancing" at each centre Comment: no information of what "dynamic balancing" entailed
Allocation concealment (selection bias)	Unclear risk	Not stated Comment: impossible to know if participants or physicians were blinded to the allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "double blind" Comment: appears adequate
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "double blind" Comment: appears adequate
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Interim analysis reviewed by an independent data and safety monitoring board." Data excluded for "6 patients who were discovered to have met an exclusion criteria, for 2 patients who did not receive IV steroid despite randomisation into this group, and 8 patients who were enrolled because they had coronary abnormalities but did not meet the classic criteria for KD."
Selective reporting (reporting bias)	Low risk	Pre‐trial protocol published on ClinicalTrials.gov and consistent with methodology and results published
Other bias	Low risk	None identified