Kawasaki disease (KD) is an acute systemic inflammatory vasculitis affecting mainly infants and children that was first described in 1967 by Kawasaki et al1,2. Its most severe complication is the formation of coronary artery abnormalities (CAAs), including coronary artery dilatation, artery fistula, myocardial infarction, and coronary artery aneurysm formation, in 15% to 25% of untreated patients3. Promptly receiving effective treatment, however, is capable to sharply reduce the risk of CAA4,5.

The scientific statement published by the American Heart Association (AHA) in 2017 recommended that the standard initial treatment of KD is high-dose intravenous immunoglobulin (IVIG) (level of evidence A), along with acetylsalicylic acid (aspirin) (level of evidence C)6. The dose regimen of IVIG, 2g/kg and usually given as a single infusion, is well established and has been unequivocally demonstrated to significantly reduce the occurrence of CAA7,8. The optimal dose of aspirin, by contrast, remains unclear, resulting in practice variation across medical centers and countries. Administration of anti-inflammatory dose (≥30mg·kg−1·d−1) aspirin until the patient is afebrile has been common practice. Upon anti-inflammatory aspirin is discontinued, anti-platelet dose aspirin (3–5mg·kg−1·d−1) is prescribed and continued until the patient has no evidence of CAA formation. Aspirin was used for both its anti-inflammatory and anti-platelet effects and has been shown to suppress the development of CAA before the spread of IVIG therapy9.‍ Since IVIG became the cornerstone of treatment, a growing number of experts have raised the question of whether higher-dose aspirin would be superior to lower-dose for the initial treatment. However, some retrospective studies to date have failed to demonstrate any benefit of anti-inflammatory dose of aspirin in preventing CAAs and several meta-analyses showed that the incidence of CAAs was dependent on the IVIG dose but independent of the aspirin dose10, 11, 12, 13, 14, 15. In addition, the administration of anti-inflammatory doses of aspirin may give rise to gastrointestinal symptoms, impaired hepatic function, and anaemia16, 17, 18, 19. Reye's syndrome, albeit rare, represents a significant complication20. Aspirin-associated asthma has also been reported21,22. Given the concerns about the unclear efficacy and potential side effects, controversies exist over the appropriate dosage of aspirin in the initial treatment of KD. Thus, it is currently incapable of providing appropriate recommendations based on evidence.

Therefore, based on the aforementioned concepts, this protocol described a multi-center randomized controlled trial to evaluate if low-dose aspirin during initial therapy of KD is non-inferior to moderate-dose aspirin.