Etanercept in Kawasaki Disease
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|ClinicalTrials.gov Identifier: NCT00841789|
Recruitment Status : Unknown
Verified April 2018 by Michael Portman, Seattle Children's Hospital.
Recruitment status was: Active, not recruiting
First Posted : February 11, 2009
Last Update Posted : April 18, 2018
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|Condition or disease||Intervention/treatment||Phase|
|Mucocutaneous Lymph Node Syndrome Kawasaki Disease||Drug: Etanercept Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||196 participants|
|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)|
|Official Title:||A Randomized, Double Blind, Placebo Controlled Study of the Effects of Etanercept in Children Presenting With Kawasaki Disease|
|Study Start Date :||March 2009|
|Actual Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||August 2018|
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.
- 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) 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.
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|Ages Eligible for Study:||2 Months to 20 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Male Age 2 months to 20 years of age Female Age 2 months to 11 years of age
- Provision of Parental Consent
- Kawasaki Disease Presentation
Laboratory Criteria: Any laboratory toxicity, at the time of the screening visit or at any time during the study that in the opinion of the Investigator would preclude participation in the study or:
- Platelet count < 100,000/mm3
- WBC count < 3,000 cells/mm3
- Hemoglobin, hematocrit, or red blood cell count outside 30% of the upper or lower limits of normal for the Lab
- Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.
- Female subjects diagnosed with KD 12 years of age and older.
- Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept
- Prior or concurrent cyclophosphamide therapy
- Prior treatment with any TNF alpha antagonist or steroid within 48 hours prior to initiation of IVIG
- Concurrent sulfasalazine therapy
- Active severe infections within 4 weeks before screening visit, or between the screening and baseline visits.
- SLE, history of multiple sclerosis, transverse myelitis, optic neuritis, or chronic seizure disorder
- Known HIV-positive status or known history of any other immuno-suppressing disease.
- Any mycobacterial disease or high risk factors for tuberculosis, such as family member with TB or taking INH
- Untreated Lyme disease
- Severe comorbidities (diabetes mellitus requiring insulin, CHF of any severity, MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris, uncontrolled hypertension (sitting systolic BP > 160 or diastolic BP > 100 mm Hg), oxygen-dependent severe pulmonary disease, history of cancer within 5 years [other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer])
- Exposure to hepatitis B or hepatitis C or high risk factors such as intravenous drug abuse in patient's mother, or history of jaundice (other than neonatal jaundice). SLE, history of multiple sclerosis, transverse myelitis, optic neuritis or chronic seizure disorder.
- Use of a live vaccine (Measles Mumps Rubella or Varicella) 30 days prior to or during this study.
- Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient
- History of non-compliance with other therapies
- Must not have received immunosuppressive agents for at least three months prior to enrollment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00841789
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467|
|Feinstein Institute for Medical Rsearch|
|New Hyde Park, New York, United States, 11040|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|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|
|Responsible Party:||Michael Portman, Cardiologist, Seattle Children's Hospital|
|Other Study ID Numbers:||
FD003526 ( Other Grant/Funding Number: FD )
|First Posted:||February 11, 2009 Key Record Dates|
|Last Update Posted:||April 18, 2018|
|Last Verified:||April 2018|
Mucocutaneous Lymph Node Syndrome
Skin Diseases, Vascular
Anti-Inflammatory Agents, Non-Steroidal
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs