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| Name | Class |
|---|---|
| Patient-Centered Outcomes Research Institute | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IVIG | Active Comparator | Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion |
|
| Infliximab | Active Comparator | Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IVIG | Drug | Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Change in Zworst Score Between Baseline and 2-week (± 4 Days) Echocardiograms |
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Inclusion Criteria:
Eligible subjects will be as follows:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jane C Burns, MD | UCSD | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UAB Children's of Alabama | Birmingham | Alabama | 35233 | United States | ||
| Arkansas Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34715057 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | IVIG | Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours |
| FG001 | Infliximab |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 14, 2019 |
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| Infliximab | Drug | Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours |
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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 |
| 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 |
| Duration of Hospitalization | How long a participant was hospitalized for. | 2 weeks |
| Number of Participants With IVIG and Infliximab Infusion Reactions and Complications | Determine any complications and/or reactions to each treatment. | 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. | 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. | 24h |
| Little Rock |
| Arkansas |
| 72202 |
| United States |
| University of California San Diego | La Jolla | California | 92093 | United States |
| Memorial Care | Long Beach | California | 90806 | United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| David Geffen School of Medicine at UCLA | Los Angeles | California | 90095 | United States |
| Harbor-UCLA Medical Center | Los Angeles | California | 90502 | United States |
| UCSF Benioff Children's Hospital-Oakland | Oakland | California | 94609 | United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| UCSF Benioff Children's Hospital-San Francisco | San Francisco | California | 94920 | United States |
| Cedar-Sinai Medical Center | West Hollywood | California | 94305 | United States |
| Children's Hospital of Colorado | Aurora | Colorado | 80045 | United States |
| Children's National Health SYstem | Washington D.C. | District of Columbia | 20010 | United States |
| Children's Healthcare of Atlanta | Atlanta | Georgia | 30322 | United States |
| Comer Children's Hospital | Chicago | Illinois | 60637 | United States |
| Riley Children's Health Indiana University School of Medicine | Indianapolis | Indiana | 46202 | United States |
| Boston Children's hospital | Boston | Massachusetts | 02115 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| Children's Mercy Kansas Ciry | Kansas City | Missouri | 64108 | United States |
| University of Nebraska Medical Center | Omaha | Nebraska | 68198 | United States |
| Maria Fareri Children's Hospital | Valhalla | New York | 10595 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| University of South Dakota Sanford School of Medicine | Sioux Falls | South Dakota | 57105 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Children's Medical Center of Dallas | Dallas | Texas | 75235 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| Primary Care University of Utah | Salt Lake City | Utah | 84113 | United States |
| Seattle Children's | Seattle | Washington | 98101 | United States |
Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours
Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours
| Participants Who Failed 1st Treatment and Crossed Over to Receive Other Treatment |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | IVIG | Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours |
| BG001 | Infliximab | Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| WBC(white blood cells count) | Median | Inter-Quartile Range | cells*10^9/L |
| |||||||||||||||
| Z-Worst | Z-Worst defined as the greatest internal diameter of the right or left anterior descending coronary artery normalized for body surface area. A Z-score >= 2.5 is considered a aneurysm according to the American Heart Association criteria. | Median | Inter-Quartile Range | Standard Deviation units |
| ||||||||||||||
| Illness Day at first IVIG | Illness Day at first IVIG treatment for KD, before enrollment into the study | Median | Inter-Quartile Range | days |
| ||||||||||||||
| Incomplete KD | Meets 2017 AHA criteria for incomplete KD | Count of Participants | Participants |
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| ANC (absolute neutrophil count | Median | Inter-Quartile Range | cells |
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| zHgb | Hemoglobin concentration normalized for age; | Median | Inter-Quartile Range | g/dL |
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| PLT (platelet count) | Median | Inter-Quartile Range | cells*10^9/L |
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| ESR (erythrocyte sedimentation rate), | Median | Inter-Quartile Range | mm/h |
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| CRP (C-reactive protein) | Median | Inter-Quartile Range | mg/dL |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | 7 days |
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| 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. | Posted | Median | Inter-Quartile Range | cells* 10^9/L | 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. | Posted | Median | Inter-Quartile Range | Standard Deviation units | 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. | Posted | Median | Inter-Quartile Range | days | 7 days |
|
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| Secondary | Duration of Hospitalization | How long a participant was hospitalized for. | Posted | Median | Inter-Quartile Range | days | 2 weeks |
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| Secondary | Number of Participants With IVIG and Infliximab Infusion Reactions and Complications | Determine any complications and/or reactions to each treatment. | Posted | Count of Participants | Participants | 7 days |
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| 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. | Posted | Median | Inter-Quartile Range | cells | 24h |
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| 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. | Posted | Median | Inter-Quartile Range | mg/dL | 24h |
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Adverse event data were collected during the entirety of the study participation which was 6 weeks from study enrollment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IVIG | Patient will be randomly assigned to receive a second IVIG infusion: 2 g/kg IV over 8-10 hours single infusion IVIG: Subjects randomized to this arm will receive IVIG 2g/kg over 10-12 hours | 0 | 49 | 27 | 49 | 6 | 49 |
| EG001 | Infliximab | Patient will be randomly assigned to receive Infliximab 10 mg/kg IV over 2 hours Infliximab: Subjects randomized to this arm will receive infliximab 10 mg/kg over 2 hours | 0 | 54 | 10 | 54 | 14 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemolytic Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Continued Fever after treatment completion and crossover to other study treatment | General disorders | Systematic Assessment |
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| Fever following crossover treatment | General disorders | Systematic Assessment |
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| Dress Syndrome | Immune system disorders | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI Symptoms | Gastrointestinal disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Arthritis/pain and swelling in extremities | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Epistaxis | Blood and lymphatic system disorders | Systematic Assessment |
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| Fever after discharge not attributed to KD | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| URI | Infections and infestations | Systematic Assessment |
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| Leukemoid Reaction | Blood and lymphatic system disorders | Systematic Assessment |
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| Chest Pain | General disorders | Systematic Assessment |
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| Hyperhidrosis | General disorders | Systematic Assessment |
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| Pain (IV Site) | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Color Blindness | Eye disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jane Burns | Dept. of Pediatrics UCSD School of Medicine | 858-246-0155 | jcburns@health.ucsd.edu |
| Aug 29, 2021 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009080 | Mucocutaneous Lymph Node Syndrome |
| ID | Term |
|---|---|
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D016756 | Immunoglobulins, Intravenous |
| D000069285 | Infliximab |
| ID | Term |
|---|---|
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000911 | Antibodies, Monoclonal |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Black or African American |
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| White |
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| Other |
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| Multi-race |
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| Unknown |
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