Kawasaki Disease

For patients with severe Kawasaki disease who respond poorly to intravenous immunoglobulin (IVIG), no established treatment strategy has been available. In 2020, cyclosporin A was approved for the treatment of severe Kawasaki disease.This study extends beyond severe cases and will evaluate combination therapy with IVIG and cyclosporin A in all patients with Kawasaki disease. Although several risk prediction models have been developed, they are not fully reliable, and even patients classified as low risk may fail to respond to IVIG. Furthermore, there is currently no clear strategy for selecting among available therapeutic options, and cyclosporin A is not reimbursed for low-risk patients, limiting its clinical use.The objective of this study is to identify the patient characteristics most likely to benefit from cyclosporin A by administering IVIG plus cyclosporin A across the full spectrum of Kawasaki disease. The findings are expected to establish evidence-based criteria for the appropriate use of IVIG, corticosteroids, and cyclosporin A, support their incorporation into clinical guidelines, and ultimately reduce the incidence of coronary artery aneurysm and other long-term complications associated with Kawasaki disease.

Sandimmun Neoral Solution

Ciclosporin A

Solution

100 mg/mL

1. Primary Endpoint：
Presence or absence of coronary artery lesion and genotypes of ITPKC SNV (rs28493229; G/C)
2. Secondary Endpoint：
Relationship between the presence or absence of coronary artery lesion corresponding to Z score of 2.5 or higher or 3.0 or higher within the study period (for 4 weeks after the registration) and following items:
1)Genotypes of ITPKC and CASP3 SNV (rs28493229; G/C and rs113420705; G/A)
2)Hematology test values (including hematocrit)
3)Biochemical test values (including total bilirubin)
4)Blood cytokine/chemokine levels before the treatment
5)Myl9 levels

Pediatric patients who meet the revised Diagnostic Guidelines for Kawasaki Disease version 6
1. Fever
2. Bilateral bulbar conjunctival congestion
3. Changes of lips and oral cavity: reddening of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa
4. Rash (including redness at the site of Bacille Calmette-Guèrin [BCG] inoculation)
5. Changes of peripheral extremities: (Initial stage) reddening of palms and soles, indurative edema; (Convalescent stage) membranous desquamation from fingertips
6. Acute non-purulent cervical lymphadenopathy
At least 5 of the above 6 principal symptoms should be satisfied for diagnosis of Kawasaki Disease. However, patients with 4 of these principal symptoms can be diagnosed with Kawasaki Disease based on the reference provisions, etc., and are included in pediatric patients subject to the treatment as suspected cases. Even if infection is identified, when a physician considers Kawasaki disease as a main disease condition, the patient will be included in the pediatric patients subject to the treatment.
2) Pediatric patients aged 4 months or older and younger than 15 years at the time of informed consent
3) Pediatric patients for whom diagnosis was made before Disease Day 9 (The day on which fever developed is defined as Disease Day 1)
4) Pediatric patients whose legal representative provided the consent in writing

1. Pediatric patients who achieved defervescence before registration
2. Pediatric patients whose main disease condition is likely to be hemolytic streptococcal infection, EB virus infection, adenovirus infection, Yersinia infection, measles, or Stevens-Johnson syndrome, which are diseases similar to Kawasaki disease
3. Pediatric patients who started to receive treatment on or after Disease Day 9
4. Pediatric patients who are receiving tacrolimus (excluding topical preparation), pitavastatin, rosuvastatin, bosentan, or aliskiren
5. Pediatric patients who had experienced hypersensitivity to ciclosporin preparation, immunoglobulin preparation, or aspirin in the past
6. Pediatric patients whose condition is complicated by active bacterial infections including sepsis, purulent meningitis, peritonitis, and bacterial pneumonia
7. Pediatric patients who received administration of another study medication within 12 weeks before the start of study medication administration
8. Pediatric patients who were vaccinated with live vaccine/BCG within 4 weeks before the start of study medication administration or inactivated vaccine within 2 weeks before the start of study medication administration
9. Other pediatric patients who were judged to be ineligible for safe implementation of this study by the investigators or the sub-investigators.