KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)

Study Overview
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Brief Summary
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Kawasaki disease (KD) is a self-limited illness that affects the heart blood vessels (coronary arteries) of infants and children and is now the most common cause of acquired heart disease in children. A mixture of proteins from human blood (Intravenous immunoglobulin, IVIG) is a treatment that reduces the rate of the major complication of the disease: a bulging of the wall of the coronary arteries called an aneurysm. However, 10-20% of children are resistant to this treatment and the fever returns. These children have the highest rates of aneurysm formation and thus should be treated aggressively. Unfortunately, there are no guidelines for the best secondary treatment for these resistant patients because the problem has never been adequately studied. Most physicians choose either a second infusion of IVIG or an engineered antibody called infliximab that inactivates a molecule that promotes inflammation. This trial will randomize (assign by chance like the flip of a coin) IVIG-resistant patients to receive either a second IVIG infusion or infliximab and the response to treatment will be compared to learn which treatment stops the fever the fastest. In addition, parents and caregivers will provide observations about their child's response to the different treatments.

Detailed Description
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This is a 3-year (2.75-years of enrollment), Phase III, two-arm, randomized, multi-center, superiority treatment study to compare infliximab to a second intravenous immunoglobulin (IVIG) infusion for treatment of persistent or recrudescent fever in children with KD who fail to become afebrile after the first IVIG infusion. Specific aim 1 will test the hypothesis that infliximab will be superior to a second intravenous immunoglobulin (IVIG) infusion for treatment of persistent or recrudescent fever in children with KD who fail to become afebrile after the first IVIG infusion (resistant KD). Cessation of fever (<38°C rectally or orally) within 24h of initiation of study treatment infusion will be the primary outcome measure. Specific aim 2 will test the hypothesis that infliximab treatment will result in more rapid resolution of inflammation compared to second IVIG as measured by the change in white blood cell count (WBC), absolute neutrophil count (ANC), and high-sensitivity C-reactive protein (hsCRP) concentration between baseline and 24 hours and 2 weeks following study treatment. Specific aim 3 will test the hypothesis that infliximab treatment will result in a reduction from baseline in coronary artery Zworst score of ≥ 0.05 standard deviation units as compared to second IVIG at 2 weeks following study treatment measured by echocardiography.

Official Title
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KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)

Conditions
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Mucocutaneous Lymph Node Syndrome

Intervention / Treatment
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* Drug: IVIG
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects will be as follows: 4 weeks to 17 years of age, fulfill the American Heart Association case definition for complete or incomplete KD, have had fever (T ≥38°C) for 3 to 10 days prior to initial IVIG treatment, have fever (T ≥38°C orally or rectally) between 36 hours and 7 days after end of the first IVIG infusion without other likely cause Exclusion Criteria: Patient treated with infliximab or steroids for present illness (pts who received oral steroids as outpatients prior to KD diagnosis but who otherwise qualify for the study will not be excluded) Known prior infection with tuberculosis, coccidiomycosis, or histoplasmosis.

Ages Eligible for Study
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Maximum Age: 17 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IVIG<br>Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion | Drug: IVIG<br>* Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours<br>* Other names: Intravenous immunoglobulin;|
| Active Comparator: Infliximab<br>Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours | Drug: Infliximab<br>* Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours<br>* Other names: Remicade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cessation of Fever Within 24h of Initiation of Study Treatment With no Fever Recurrence Within Next 7 Days. | A fever will be considered ≥38°C rectally or orally and ≥ 37.5°C axillary. Cessation of fever within 24h of initiation of study treatment with no fever recurrence within next 7 days. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in White Blood Cell Count (WBC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. | Change in white blood cell count (WBC), between baseline and 24 hours and 2 weeks following study treatment. | 24h | 
| Change in Zworst Score Between Baseline and 2-week (± 4 Days) Echocardiograms | Zworst score is defined as the largest internal diameter of either the right coronary or left anterior descending arteries normalized for body surface area and expressed as standard deviation units from the mean. A Z-score >= 2.5 is considered a aneurysm according to the American Heart Association criteria. | 2 weeks | 
| Total Number of Fever Days (24 Hour Period With a T≥38.0°C) From Enrollment | Determine the number of days a participant had a fever once the participant has been enrolled into the study. | 7 days | 
| Duration of Hospitalization | How long a participant was hospitalized for. | 2 weeks | 
| Number of Participants With IVIG and Infliximab Infusion Reactions and Complications | Determine any complications and/or reactions to each treatment. | 7 days | 
| Change in Absolute Neutrophil Count (ANC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. | Change in absolute neutrophil count (ANC) between baseline and 24 hours and 2 weeks following study treatment. | 24h | 
| Change in C-reactive Protein (CRP, mg/dL) Concentration Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. | Change in C-reactive protein (CRP, mg/dL) concentration between baseline and 24 hours and 2 weeks following study treatment. | 24h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kawasaki disease