Clinical trial NCT03065244: KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
Official title: KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mucocutaneous Lymph Node Syndrome
Keywords: Kawasaki disease
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2017-02-27
Enrollment: 105
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Cessation of Fever Within 24h of Initiation of Study Treatment With no Fever Recurrence Within Next 7 Days.
timeFrame: 7 days
Secondary outcomes:
measure: Change in White Blood Cell Count (WBC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment.
timeFrame: 24h
measure: Change in Zworst Score Between Baseline and 2-week (± 4 Days) Echocardiograms
timeFrame: 2 weeks
measure: Total Number of Fever Days (24 Hour Period With a T≥38.0°C) From Enrollment
timeFrame: 7 days
measure: Duration of Hospitalization
timeFrame: 2 weeks
measure: Number of Participants With IVIG and Infliximab Infusion Reactions and Complications
timeFrame: 7 days
measure: Change in Absolute Neutrophil Count (ANC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment.
timeFrame: 24h
measure: Change in C-reactive Protein (CRP, mg/dL) Concentration Between Baseline and 24 Hours and 2 Weeks Following Study Treatment.
timeFrame: 24h
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Children's of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Long Beach
country: United States
facility: Memorial Care
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Los Angeles
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital-Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital-San Francisco
state: California
city: West Hollywood
country: United States
facility: Cedar-Sinai Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Health SYstem
state: District of Columbia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Comer Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Health Indiana University School of Medicine
state: Indiana
city: Boston
country: United States
facility: Boston Children's hospital
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Kansas Ciry
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Sioux Falls
country: United States
facility: University of South Dakota Sanford School of Medicine
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Care University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
Study officials:
affiliation: UCSD
name: Jane C Burns, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.