Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD-CAA Prevention (KD-CAAP) trial

Journal article

Background:
Kawasaki disease (KD) is a childhood vasculitis affecting medium-sized arteries, particularly the coronary arteries. Despite treatment with intravenous immunoglobulin (IVIG), coronary artery aneurysm (CAA) rates remain high in Europe and North America. The KD-CAAP trial evaluated whether adjunctive prednisolone reduces CAA in unselected European children with KD.
Methods:
This multicentre, randomised, open-label, blinded endpoint-assessed, superiority trial (ISRCTN71987471) enrolled children aged 30 days to 16 years across 59 centres in 12 European countries. Participants were randomised 1:1 to oral prednisolone (2 mg/kg/day) plus IVIG (2 g/kg) and aspirin (experimental group); or IVIG and aspirin (control group), stratified by age (<1 vs ≥1 year), sex and country. Co-primary outcomes were: CAA within 12 weeks and mean maximum coronary artery z-score across weeks 1-6, analysed using intention-totreat.
Findings:
Between Jan 2021-July 2024, 103 children (58% male; median age 2 years) were randomised: 50 to experimental and 53 to control groups. All children received IVIG+aspirin; fewer experimental participants received a second IVIG dose [9 (18%) vs 20 (38%) control, p=0.021] or rescue therapy [8 (16%) vs 17 (32%), respectively, p=0.044]. CAA occurred in 12/50 (24%) experimental vs 12/53 (23%) control participants (adjusted risk difference +1.1% (95% credibility interval -13.8% to 16.1%), with 45% probability of benefit. There was no evidence of difference in mean maximum coronary z-scores over weeks 1-6 (mean 0.6 (95% confidence interval 0.4-0.9) vs 0.7 (0.4-0.9); adjusted difference –0.0; 95% confidence interval –0.2 to +0.2; p=0.72). CAA developed in 6/12 (50%) infants <1 year. Serious Adverse Events occurred in 7 (14%) experimental vs 3 (6%) control participants (p=0.19). Costs were significantly lower in the experimental group due to less IVIG use over 12 weeks.
Interpretation:
Prednisolone reduced treatment escalation, with potential health economic benefits, but did not reduce CAA in unselected European children with KD. CAA rates remained high, particularly in infants.

Authors: Eleftheriou, D; Connon, R; Tulloh, R; Martin, N; Kucera, F

• Publication status: Accepted
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: EClinicalMedicine
• Acceptance date: 2026-06-12
• EISSN: 2589-5370
• Language: English