Mucocutaneous Lymph Node SyndromePhase 3KIDCARENCT03065244
KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
A Phase 3 study testing IVIG and Infliximab in people with Mucocutaneous Lymph Node Syndrome, run by University of California, San Diego at 29 sites in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Mucocutaneous Lymph Node Syndrome
- What is being tested?
- IVIG and Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 29 sitesUnited States
- Study dates
- 17 Feb 2017to 2 Nov 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital of Colorado
Aurora, Colorado, 80045
UAB Children's of Alabama
Birmingham, Alabama, 35233
Boston Children's hospital
Boston, Massachusetts, 02115
Comer Children's Hospital
Chicago, Illinois, 60637
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Medical Center of Dallas
Dallas, Texas, 75235
Children's Hospital of Michigan
Detroit, Michigan, 48201
Texas Children's Hospital
Houston, Texas, 77030
Riley Children's Health Indiana University School of Medicine
Indianapolis, Indiana, 46202
Children's Mercy Kansas Ciry
Kansas City, Missouri, 64108
University of California San Diego
La Jolla, California, 92093
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Memorial Care
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
Harbor-UCLA Medical Center
Los Angeles, California, 90502
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
UCSF Benioff Children's Hospital-Oakland
Oakland, California, 94609
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Primary Care University of Utah
Salt Lake City, Utah, 84113
UCSF Benioff Children's Hospital-San Francisco
San Francisco, California, 94920
Seattle Children's
Seattle, Washington, 98101
University of South Dakota Sanford School of Medicine
Sioux Falls, South Dakota, 57105
Maria Fareri Children's Hospital
Valhalla, New York, 10595
Children's National Health SYstem
Washington D.C., District of Columbia, 20010
Cedar-Sinai Medical Center
West Hollywood, California, 94305
About this study
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.
Read the 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.
- 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.
- 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.
- 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
- Being tested
- IVIG, Infliximab
- Keywords
- Kawasaki disease
- Medical subject headings
- Mucocutaneous Lymph Node Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVIGDrug
Also called Intravenous immunoglobulin
Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours
InfliximabDrug
Also called Remicade
Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
| Study group | Role | What they receive |
|---|---|---|
| IVIG | Active comparator | Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion Receives: Drug: IVIG |
| Infliximab | Active comparator | Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days
Secondary outcomes (7)
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.
Measured: 24h
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.
Measured: 2 weeks
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.
Measured: 7 days
Duration of Hospitalization
How long a participant was hospitalized for.
Measured: 2 weeks
Number of Participants With IVIG and Infliximab Infusion Reactions and Complications
Determine any complications and/or reactions to each treatment.
Measured: 7 days
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.
Measured: 24h
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.
Measured: 24h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2017
- Study start17 Feb 2017
- Primary completion31 Aug 2020
- Study completion2 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mucocutaneous Lymph Node SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Jane C. Burns MD, University of California, San Diego
- Investigators
- Jane C Burns, MD, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03065244
- Sponsor's protocol ID
- UCSD 170064
- Acronym
- KIDCARE
- Status last verified
- Aug 2021
- First submitted
- 17 Jan 2017
- Last updated
- 3 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34715057
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
- ClinicalTrials.gov ID
- NCT03065244
- Acronym / sponsor ID
- KIDCARE / UCSD 170064
- Conditions
- Mucocutaneous Lymph Node Syndrome
- Keywords
- Kawasaki disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Study start
- 17 Feb 2017 (actual)
- Primary completion
- 31 Aug 2020 (actual)
- Study completion
- 2 Nov 2020 (actual)
- First posted
- 27 Feb 2017 (actual)
- Results
- Posted 3 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
- 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.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IVIG | Active comparator | Drug: IVIGPatient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion |
| Infliximab | Active comparator | Drug: InfliximabPatient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Eligible subjects will be as follows:
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVIGAlso: Intravenous immunoglobulinSubjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours | Drug | IVIG |
| InfliximabAlso: RemicadeSubjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours | Drug | Infliximab |
Primary outcome
Number of Participants With 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.
7 secondary outcomes
Change in White Blood Cell Count (WBC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment.
Time frame: 24h
Change in Zworst Score Between Baseline and 2-week (± 4 Days) Echocardiograms
Time frame: 2 weeks
Total Number of Fever Days (24 Hour Period With a T≥38.0°C) From Enrollment
Time frame: 7 days
Duration of Hospitalization
Time frame: 2 weeks
Number of Participants With IVIG and Infliximab Infusion Reactions and Complications
Time frame: 7 days
Change in Absolute Neutrophil Count (ANC) Between Baseline and 24 Hours and 2 Weeks Following Study Treatment.
Time frame: 24h
Change in C-reactive Protein (CRP, mg/dL) Concentration Between Baseline and 24 Hours and 2 Weeks Following Study Treatment.
Time frame: 24h
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34715057Burns 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane C Burns, MD principal investigator
UCSD
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IVIG and Infliximab in people with Mucocutaneous Lymph Node Syndrome, run by University of California, San Diego at 29 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Cessation of Fever Within 24h of Initiation of Study Treatment With no Fever Recurrence Within Next 7 Days. (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03065244, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2021.