KIDCARE (Kawasaki Disease Comparative Effectiveness Trial) (KIDCARE)

• ClinicalTrials.gov Identifier: NCT03065244
• Recruitment Status: Recruiting
• First Posted: February 27, 2017
• Last Update Posted: April 22, 2019
• Sponsor: University of California, San Diego
• Collaborator: Patient-Centered Outcomes Research Institute
• Information provided by (Responsible Party): Jane C. Burns MD, University of California, San Diego

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mucocutaneous Lymph Node Syndrome	Drug: IVIG; Drug: Infliximab	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
• Actual Study Start Date: February 17, 2017
• Estimated Primary Completion Date: January 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: IVIG; Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion	Drug: IVIG; Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours; Other Name: Intravenous immunoglobulin
Active Comparator: Infliximab; Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours	Drug: Infliximab; Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours; Other Name: Remicade

Outcome Measures

Primary Outcome Measures :

1. Cessation of fever within 24h of initiation of study treatment with no fever recurrence within next 7 days. [ Time Frame: 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 :

1. Cessation of fever within 24h following completion of treatment infusion (Length of infusion is 2h for infliximab and 8-10h for second IVIG) [ Time Frame: 24 h ]
   A fever will be considered ≥38°C rectally or orally and ≥ 37.5°C axillary. Cessation of fever within 24h following completion of treatment infusion (Length of infusion is 2h for infliximab and 8-10h for second IVIG).
2. Change in white blood cell count (WBC), absolute neutrophil count (ANC), and high-sensitivity C-reactive protein (hsCRP, mg/L) concentration between baseline and 24 hours and 2 weeks following study treatment. [ Time Frame: 24h ]
   Change in white blood cell count (WBC), absolute neutrophil count (ANC), and high-sensitivity C-reactive protein (hsCRP, mg/L) concentration between baseline and 24 hours and 2 weeks following study treatment.
3. Change in Zworst score between baseline and 2-week (± 4 days) echocardiograms [ Time Frame: 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.
4. Total number of fever days (24 hour period with a T≥38.0°C) from enrollment [ Time Frame: 7 days ]
   Determine the number of days a participant had a fever once the participant has been enrolled into the study.
5. Duration of hospitalization [ Time Frame: 2 weeks ]
   How long a participant was hospitalized for.
6. IVIG and infliximab infusion reactions and complications [ Time Frame: 7 days ]
   Determine any complications and/or reactions to each treatment.

Eligibility Criteria

• Ages Eligible for Study: up to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Jane C Burns, MD; 858-246-0155; jcburns@ucsd.edu

Contact: Adriana H Tremoulet, MD; 858-246-0012; atremoulet@ucsd.edu

Locations

United States, California

University of California San Diego; Recruiting

La Jolla, California, United States, 92093

Contact: Jane C Burns, MD 858-246-0155 jcburns@ucsd.edu

Contact: Adriana H Tremoulet, MD 858-966-0012 atremoulet@ucsd.edu

Sponsors and Collaborators

University of California, San Diego

Patient-Centered Outcomes Research Institute

Investigators

• Principal Investigator: Jane C Burns, MD; UCSD

More Information

• Responsible Party: Jane C. Burns MD, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03065244
• Other Study ID Numbers: UCSD 170064
• First Posted: February 27, 2017
• Last Update Posted: April 22, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Jane C. Burns MD, University of California, San Diego:

Kawasaki disease

Additional relevant MeSH terms:

Mucocutaneous Lymph Node Syndrome; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Infliximab; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunologic Factors; Physiological Effects of Drugs; Dermatologic Agents; Gastrointestinal Agents; Antirheumatic Agents