Etanercept in Kawasaki Disease
|Mucocutaneous Lymph Node Syndrome Kawasaki Disease||Drug: Etanercept Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Approximately 200 subjects will be randomized in a 1:1 ratio to receive Etanercept or Placebo. Subjects are randomized after hospital admission and diagnosis of Kawasaki Disease at eight participating sites. The primary analysis time-point is visit 5 (day 44). Sample size calculation is based on initial IVIG refractory rate at Seattle Children's. Assuming a 17.4% refractory rate in the control group and a 4.3% refractory rate in the Etanercept group, 200 subjects will provide 80% power at a 5% 2-sided type I error rate. Analyses will be based on a modified intention to treat population, including all subjects who were randomized and received at least 1 dose of study drug. Efficacy analyses will be based on randomization assignment, and safety analyses will be based on the treatment actually received. The statistical analysis plan will be finalized prior to database lock and study unblinding.Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double Blind, Placebo Controlled Study of the Effects of Etanercept in Children Presenting With Kawasaki Disease|
- Determine if Etanercept at the dosing regimen of 0.8 mg/kg (50 mg max) SQ X3 doses given at weekly intervals, when used in conjunction with IVIG and aspirin will reduce the incidence of fever persistence or recrudescence. [ Time Frame: 42 days after initial dose ]The primary outcome is the proportion of subjects who become refractory to IVIG. Subjects requiring 1 dose of IVIG are classified as responders and subjects requiring more than 1 dose are classified as IVIG refractory.
- Determine if the safety profile differs between the etanercept treated group and the placebo group. [ Time Frame: 42 days after initial dose ]The proportion of subjects with serious adverse events and hospital re-admissions prior to visit 5 will be compared using the chi-square test or Fisher's Exact test, as appropriate. The incidence of individual adverse events and serious adverse events will be tabulated using the Pediatric Heart Network Classification System.
- Determine if Etanercept treatment alters the rate of coronary artery dilation and disease (CAD) defined by z-scores at 2 and 6 weeks after treatment. [ Time Frame: 42 days after initial dose ]
The primary echocardiographic outcome will be the proportion of subjects with improvement defined as (20% change in coronary artery) from the worst findings during the acute study period (scheduled visits from admission to visit 4, including any unscheduled visits) to the primary study outcome time-point at visit 5 (visit 5). This calculation will be based on changes in absolute values and not z-scores as initially planned. Groups will be compared using a logistic model including a binary term for age < versus > 1 year. Two aspects of the echo findings will be considered:
- Maximum aneurysm size and
- Maximum measurements for left main coronary artery (LMCA), left anterior descending artery (LAD) and right coronary artery (RCA).
- Change in diameter of each coronary artery will be determined at standard measurement location or aneurysm with the latter taking precedent.
- CRP Laboratory Measurements [ Time Frame: 42 days after initial dose ]
Time to return to normal levels of C-Reactive protein (CRP) from admission to the visit 5 visit will be compared using Kaplan-Meier Curves. If the proportional hazards assumption is not violated, Cox Proportional Hazards Regression will be used to calculate hazard ratios.
The proportion of subjects with normal CRP levels at the visit 5 visit will be tabulated and 95% confidence intervals will be produced.
- Hemoglobin Laboratory Measurements [ Time Frame: 42 days after initial dose ]
Continuous change in Hemoglobin will be compared longitudinally using mixed models for repeated measures.
Maximum toxicity grade for anemia through visit 5 according to the common toxicity criteria for adverse events (Grade 1: See chart below * to < 10.0 g/dl, Grade 2: < 10.0 to 8.0 g/dl, Grade 3: < 8.0 g/dl) will be tabulated, and 95% confidence intervals will be produced for the proportions.
|Study Start Date:||March 2009|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm 1 -Etanercept
Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin
etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
Other Name: Enbrel
Placebo Comparator: 2
Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00841789
|United States, New York|
|Feinstein Institute for Medical Rsearch|
|New Hyde Park, New York, United States, 11040|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Montefiore Medical Center|
|The Bronx, New York, United States, 10467|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|United States, Utah|
|Primary Children's Medical Center|
|Salt Lake City, Utah, United States, 84113|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|United States, Wisconsin|
|Children's Hospital of Wisconsin|
|Milwaukee, Wisconsin, United States, 53201|
|Montreal, Quebec, Canada, H3T 1C5|
|Principal Investigator:||Michael A Portman, MD||Seattle Children's Hospital|