KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)

NCT ID: NCT03065244

Last Updated: 2021-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-17
• Study Completion Date: 2020-11-02

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.

Conditions

Mucocutaneous Lymph Node Syndrome

Keywords

Kawasaki disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IVIG

Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion

Group Type: ACTIVE_COMPARATOR

IVIG

Intervention Type: DRUG

Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours

Infliximab

Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours

Group Type: ACTIVE_COMPARATOR

Infliximab

Intervention Type: DRUG

Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours

Interventions

IVIG

Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours

Intervention Type: DRUG

Infliximab

Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours

Intervention Type: DRUG

Other Intervention Names

Intravenous immunoglobulin; Remicade

Eligibility Criteria

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.

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Jane C. Burns MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jane C Burns, MD

Role: PRINCIPAL_INVESTIGATOR

UCSD

Locations

UAB Children's of Alabama

Birmingham, Alabama, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

University of California San Diego

La Jolla, California, 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

UCSF Benioff Children's Hospital-Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Benioff Children's Hospital-San Francisco

San Francisco, California, United States

Cedar-Sinai Medical Center

West Hollywood, California, United States

Children's Hospital of Colorado

Aurora, Colorado, United States

Children's National Health SYstem

Washington D.C., District of Columbia, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Comer Children's Hospital

Chicago, Illinois, United States

Riley Children's Health Indiana University School of Medicine

Indianapolis, Indiana, United States

Boston Children's hospital

Boston, Massachusetts, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Children's Mercy Kansas Ciry

Kansas City, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Maria Fareri Children's Hospital

Valhalla, New York, United States

Nationwide Children's Hospital

Columbus, Ohio, 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

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Children's Medical Center of Dallas

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Primary Care University of Utah

Salt Lake City, Utah, United States

Seattle Children's

Seattle, Washington, United States

Countries

United States

References

Burns JC, Roberts SC, Tremoulet AH, He F, Printz BF, Ashouri N, Jain SS, Michalik DE, Sharma K, Truong DT, Wood JB, Kim KK, Jain S; KIDCARE Multicenter Study Group. Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial. Lancet Child Adolesc Health. 2021 Dec;5(12):852-861. doi: 10.1016/S2352-4642(21)00270-4. Epub 2021 Oct 27.

Reference Type: DERIVED

PMID: 34715057 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UCSD 170064

Identifier Type: -

Identifier Source: org_study_id