KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
- Registration Number
- NCT03065244
- Lead Sponsor
- University of California, San Diego
- Brief Summary
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
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.
1. 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.
2. 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.
3. 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 105
-
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description IVIG IVIG Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion Infliximab Infliximab Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours
- Primary Outcome Measures
Name Time Method Number of Participants With Cessation of Fever Within 24h of Initiation of Study Treatment With no Fever Recurrence Within Next 7 Days. 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.
- Secondary Outcome Measures
Name Time Method Duration of Hospitalization 2 weeks How long a participant was hospitalized for.
Number of Participants With IVIG and Infliximab Infusion Reactions and Complications 7 days Determine any complications and/or reactions to each treatment.
Change in Zworst Score Between Baseline and 2-week (± 4 Days) Echocardiograms 2 weeks 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.
Change in White Blood Cell Count (WBC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. 24h Change in white blood cell count (WBC), between baseline and 24 hours and 2 weeks following study treatment.
Total Number of Fever Days (24 Hour Period With a T≥38.0°C) From Enrollment 7 days Determine the number of days a participant had a fever once the participant has been enrolled into the study.
Change in Absolute Neutrophil Count (ANC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment. 24h Change in absolute neutrophil count (ANC) 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 Change in C-reactive protein (CRP, mg/dL) concentration between baseline and 24 hours and 2 weeks following study treatment.
Trial Locations
- Locations (29)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of South Dakota Sanford School of Medicine
🇺🇸Sioux Falls, South Dakota, United States
Boston Children's hospital
🇺🇸Boston, Massachusetts, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Memorial Care
🇺🇸Long Beach, California, United States
UCSF Benioff Children's Hospital-San Francisco
🇺🇸San Francisco, California, United States
UCSF Benioff Children's Hospital-Oakland
🇺🇸Oakland, California, United States
Comer Children's Hospital
🇺🇸Chicago, Illinois, United States
Children's Medical Center of Dallas
🇺🇸Dallas, Texas, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Riley Children's Health Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Children's Mercy Kansas Ciry
🇺🇸Kansas City, Missouri, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital of Colorado
🇺🇸Aurora, Colorado, United States
Children's National Health SYstem
🇺🇸Washington, District of Columbia, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Maria Fareri Children's Hospital
🇺🇸Valhalla, New York, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Seattle Children's
🇺🇸Seattle, Washington, United States
UAB Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Primary Care University of Utah
🇺🇸Salt Lake City, Utah, United States
Harbor-UCLA Medical Center
🇺🇸Los Angeles, California, United States
Cedar-Sinai Medical Center
🇺🇸West Hollywood, California, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States