KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)

Mucocutaneous Lymph Node Syndrome Clinical Trial

— KIDCARE  

Official title:

KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03065244
• Other study ID #: UCSD 170064
• Status: Completed
• Phase: Phase 3
• Start date: February 17, 2017
• Est. completion date: November 2, 2020

Study information

• Verified date: August 2021
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: November 2, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

• Eligible subjects will be as follows:

1. 4 weeks to 17 years of age,

2. fulfill the American Heart Association case definition for complete or incomplete KD,

3. have had fever (T =38°C) for 3 to 10 days prior to initial IVIG treatment,

4. 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:

1. 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)

2. Known prior infection with tuberculosis, coccidiomycosis, or histoplasmosis.

Related Conditions & MeSH terms

• Mucocutaneous Lymph Node Syndrome

Intervention

Drug:
• IVIG
Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours
• Infliximab
Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	UAB Children's of Alabama	Birmingham	Alabama
United States	Boston Children's hospital	Boston	Massachusetts
United States	Comer Children's Hospital	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center of Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Texas Children's Hospital	Houston	Texas
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	University of California San Diego	La Jolla	California
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Memorial Care	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Harbor-UCLA Medical Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	UCSF Benioff Children's Hospital-Oakland	Oakland	California
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Primary Care University of Utah	Salt Lake City	Utah
United States	UCSF Benioff Children's Hospital-San Francisco	San Francisco	California
United States	Seattle Children's	Seattle	Washington
United States	University of South Dakota Sanford School of Medicine	Sioux Falls	South Dakota
United States	Maria Fareri Children's Hospital	Valhalla	New York
United States	Children's National Health SYstem	Washington	District of Columbia
United States	Cedar-Sinai Medical Center	West Hollywood	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Duration of Hospitalization	How long a participant was hospitalized for.	2 weeks
Secondary	Number of Participants With IVIG and Infliximab Infusion Reactions and Complications	Determine any complications and/or reactions to each treatment.	7 days
Secondary	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
Secondary	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