Intravenous Immunoglobulin Alone for Coronary Artery Lesion Treatment of Kawasaki Disease: A Randomized Clinical Trial.

Importance: Aspirin (acetylsalicylic acid) and intravenous immunoglobulin (IVIG) are standard treatments for Kawasaki disease (KD) to reduce coronary artery lesions (CALs). However, the optimal duration and dosage of aspirin remain inconsistent across hospitals. The absence of large-scale, multicenter randomized clinical trials hinders a clear understanding of the effectiveness of high-dose aspirin. Objective: To evaluate the effectiveness of IVIG alone compared with IVIG combined with high-dose aspirin as the active interventional therapy for KD and to compare treatment effectiveness across various KD subgroups. Design, Setting, and Participants: In this prospective, evaluator-blinded, multicenter noninferiority randomized clinical trial, children (aged <6 years) who had been diagnosed with KD according to American Heart Association criteria were recruited from 5 medical centers in Taiwan and were enrolled between September 1, 2016, and August 31, 2018, with follow-up assessments at 6 weeks and 6 months after treatment. Data were analyzed between January 23, 2023, and January 29, 2024. Intervention: The standard group received IVIG (2 g/kg) plus high-dose aspirin (80-100 mg/kg per day) until fever subsided for 48 hours. The intervention group received IVIG (2 g/kg) alone. Main Outcomes and Measures: The primary outcome was the occurrence of CALs at 6 weeks. The noninferiority margin was set at 10%. Data analysis was performed using χ2 tests for categorical variables; independent t tests for continuous, normally distributed variables; generalized estimating equations for variables without specific distributions at multiple time points; and repeated-measures analysis of variance for continuous variables at multiple time points. Results: The final cohort consisted of 134 patients with KD (mean [SD] age, 1.8 [1.3] years; 82 males [61.2%]), with matched age, weight, height, and sex distributions in 2 groups. Overall, in the IVIG plus aspirin group, among 69 patients, CAL occurrence decreased from 9 (13.0%) at baseline to 2 (2.9%) at 6 weeks and to 1 (1.4%) at 6 months. In the IVIG-only group, among 65 patients, CAL occurrence decreased from 7 (10.8%) at diagnosis to 1 (1.5%) at 6 weeks and to 2 (3.1%) at 6 months. No statistically significant differences in CAL frequency were observed between the 2 groups (0.7 percentage points [95% CI, -4.5 to 5.8 percentage points]; P = .65). There were also no significant differences in the treatment or prophylactic effect. Conclusions and Relevance: This randomized clinical trial demonstrated the noninferiority of IVIG alone compared with IVIG plus aspirin, with a noninferiority margin set at 10%. The findings suggest that addition of high-dose aspirin during initial IVIG treatment is not clinically meaningful for CAL reduction in children with KD. Future studies on IVIG treatment alone for CAL reduction in KD across diverse racial and ethnic groups, beyond the Asian population, may be necessary to confirm minimal racial and ethnic variability and the broad applicability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02951234.