A Trial to Evaluate the Efficacy of Immunoglobulin Plus Steroid for Prevention of Coronary Artery Abnormalities in Taiwanese Refractory Kawasaki Disease (RAST Study)

Study Overview
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Brief Summary
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Background: Kawasaki disease (KD), most popular acquired heart disease in childhood, is characterized by diffuse vasculitis, especially on the middle-sized muscular arteries. IVIG and aspirin are currently standard treatment. However, 10-15% of KD patients have poor response to such treatment and suffer from higher risk of coronary involvement. Recently, combination of prednisolone and IVIG has been shown effective to lower the chance of refractory to IVIG treatment and subsequent coronary lesions. However, no randomized trial on the steroid efficacy was ever conducted in Taiwan. Aim: Prospectively randomized open-label trial to evaluate the add-on effect of prednisolone in the refractory KD children. Methods: For the KD patients with fever persisted or relapsed 24 hours after the ending of IVIG infusion, they will be randomized into two group: IVIG group (I) and IVIG + prednisolone group (P). The KD patients in the P group will have in addition to IVIG, oral prednisolone 2mg/kg/day for at least 5 days. The difference in the response rate and percentage of coronary involvement will be compared between I and P groups. Predicted results: We plan to enroll 100 refractory KD patients, 50 patients for each group. We predict the risk of coronary involvement can be reduced from 30% to 15%.

Official Title
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A Randomized Open-label Trial to Evaluate the Efficacy of Immunoglobulin Plus Steroid for Prevention of Coronary Artery Abnormalities in Taiwanese Refractory Kawasaki Disease (RAST Study)

Conditions
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Kawasaki Disease, Steroid, Immuoglobulin

Intervention / Treatment
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* Drug: Prednisolone
* Biological: immunoglobulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: KD (Kawasaki disease) patients who failed to respond to the initial IVIG as those who had persistent fever that lasted for more than 24 hours (nonresponse to the initial IVIG) or recrudescent fever associated with KD symptoms after an afebrile period (relapse). Exclusion Criteria: KD patients, those diagnosed on or after day 9 of illness (the first illness day was defined as the day of fever onset), those with coronary artery abnormalities before enrolment, those who were afebrile before enrolment, those who had received steroids (oral, intravenous, intramuscular, or subcutaneous) in the 30 days before the study or intravenous immunoglobulin in the previous 180 days, those with concomitant severe medical disorders (eg, immunodeficiency, chromosomal anomalies, congenital heart diseases, metabolic diseases, nephritis, collagen diseases), and those with suspected infectious disease, including sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella, and influenza.

Ages Eligible for Study
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Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: S group<br>IVIG (2g/Kg in 12 hours)+oral prednisolone (2mg/Kg/day for 5 days) | Drug: Prednisolone<br>* Prednisolone 2mg/Kg/day for 5 days<br>Biological: immunoglobulin<br>* immunoglobulin 2g/Kg for 12 hours<br>|
| Placebo Comparator: I group<br>IVIG (2g/Kg in 12 hours) | Biological: immunoglobulin<br>* immunoglobulin 2g/Kg for 12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximal coronary z score | echocardiography | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fever more than 38 degree | from end of second course of IVIG | 3 days |