Multicenter, randomized, open-label study to compare immunoglobulin to immunoglobulin plus cyclosporin A combination therapy in patients with severe Kawasaki disease
- Conditions
- Severe Kawasaki disease
- Registration Number
- JPRN-jRCT1091220174
- Lead Sponsor
- Coordinating Committee
- Brief Summary
CONCLUSIONS: We could conclude that the IVIG+CsA therapy has the possibility of being an efficaciously superior therapy to the standard therapy in terms of CAL occurrence and symptoms. Although the proportion of initial treatment nonresponders?was similar between the 2 groups overall, and was significantly lower in the IVIG+CsA group than in the IVIG group in the additional analysis result, more relapse patients were observed in the IVIG+CsA group. Regarding safety, although the overall safety results were comparable in the 2 study groups, drug-related AEs occurred at higher incidences, and relapse of Kawasaki's disease occurred at higher frequencies in the IVIG+CsA group. A higher rate of defervescence was observed, and the formation of CAL was suppressed by the use of CsA at the early stage. However, relapse of Kawasaki's disease was observed in 22 patients during/after the 5-day administration of CsA. Therefore, the relapse of Kawasaki's disease should be noted during/after the last administration of CsA. Overall, evaluation results showed that IVIG+CsA combination therapy in KD patients could be an alternative treatment for patients who are nonresponsive to the standard treatment with further investigation on the safety profile by the therapy's evident effectiveness toward CAL and other symptoms accompanied by the onset of KD. The safety profile is speculated to be fairly similar to that of the standard therapy. Further investigations should be conducted on the IVIG+CsA combination therapy for future use in clinical settings.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 172
1)Pediatric patients with a diagnosis of KD according to the Kawasaki Disease Diagnostic Guideline (the 5th revised edition).
Patients who meet 5 of the 6 main symptoms below are diagnosed as having KD.
2)Severe KD patients with a risk score of 5 points or higher.
The risk score is defined as the sum of all items in the risk-scoring system (5 blood exam data, 2 demographic data of the subjects) developed by Kobayashi et al. Of note, the risk scoring will be performed using a method employed in the previous literature in which the worst values of the blood exam obtained within the acceptable range of time points will be adopted.
3)Age of 4 months or more at the time of signing the informed consent form.
4)Inclusion in the study within 7 days of disease onset. (considering day 1 to be the day when the fever develops.)
5)Informed consent form signed by the patient or a legal guardian.
1)A history of KD recurrence.
2)CAAs prior to enrolment.
3)No presence of fever prior to enrolment.
4)Suspicion that the symptoms may correspond to a disease other than KD. (haemolytic streptococcal infection, EB virus infection, Yersinia infection, measles or Stevens-Johnson syndrome.)
5)Initiation of IVIG treatment later than 9 days after disease onset.
6)Administration of IVIG within 180 days prior to obtaining informed consent.
7)Treatment with steroids (except external preparations), steroid pulse, biological agents, neutrophil elastase inhibitors, immunosuppressants, or plasmapheresis within 30 days of screening.
8)History of hypersensitivity to CsA preparations, immunoglobulin preparations, or aspirin.
9)Having had treatment with tacrolimus, pitavastatin, rosuvastatin, bosentan, aliskiren, asunaprevir or vaniprevir.
10)Aspartate aminotransferase or, alanine aminotransferase values of 500 IU/L or higher.
11)An estimated glomerular filtration rate of 50 mL/min/1.73 m2 or lower.
12)Presence of an active bacterial infection: septicaemia, meningitis purulenta, peritonitis or bacterial pneumonia.
13)Treatment with other investigational drugs within 12 weeks of study commencement.
14)Others: patients who are judged to be inappropriate for participants of the clinical study for safety reasons by the investigators or the sub-investigators.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Frequency of CAAs during the study period (central review of echocardiography data)
- Secondary Outcome Measures
Name Time Method [Efficacy] <br>1)Frequency of CAA at week 4 <br>2)Frequency of treatment resistance (initial treatment unresponsiveness or relapse during the 12 weeks after treatment initiation.) <br>3)Z scores for the right coronary artery, and the left main coronary trunk and anterior descending artery. <br>4)Fever duration <br>5)Changes in body temperature, frequency of defervescence. <br>6)Change in serum concentration of C reactive protein (CRP). <br>7)Genotype frequency of ITPKC and CASP3 SNPs. <br>8)Additional treatment and follow-up treatment. <br><br>[Safety] <br>1)Frequency of AEs