A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease

Phase 2

Completed

Conditions: Mucocutaneous Lymph Node Syndrome
Kawasaki Disease

Interventions: Drug: Placebo
Drug: Etanercept

Registration Number: NCT00841789

Lead Sponsor: Michael Portman

Brief Summary: The purpose of this study is to determine whether Etanercept (Enbrel) when used in conjunction with IVIG and aspirin, improves treatment response to IVIG in patients with Kawasaki Disease. Funding Source- FDA/OOPD

Detailed Description: Kawasaki Disease (KD) is a potentially life threatening acute vasculitis in children with a predilection for involvement of the coronary arteries. Aspirin and Intravenous gamma globulin (IVIG) are principally used for the treatment of the symptoms of Kawasaki Disease. Aspirin reduces inflammation and platelet formation, but has no effect in attenuating the development of coronary abnormalities. Although IVIG reduces inflammation and the prevalence of coronary artery abnormalities, it has a relatively high failure rate of 23-30%, warranting new treatment methods for Kawasaki Disease. We propose a placebo controlled double blinded randomized study to determine if etanercept 0.8 mg/kg subcutaneously (max 25 mg) given three times at weekly intervals starting at initial diagnosis is safe in this patient population and if it is a successful adjunct therapy with IVIG in reducing the incidence of persistent or recurrent fever.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 205

Inclusion Criteria

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

Exclusion Criteria

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:
1. Platelet count < 100,000/mm3
2. WBC count < 3,000 cells/mm3
3. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
Arm 1 -Etanercept	Etanercept	Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin

Primary Outcome Measures

Name	Time	Method
IVIG Refractory	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.

Secondary Outcome Measures

Name	Time	Method
Determine if Etanercept Treatment Alters the Rate of Coronary Artery Dilation and Disease (CAD) at 2 and 6 Weeks After Treatment in Patients With Dilated Coro	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.

Trial Locations

Locations (8): Texas Children's Hospital
🇺🇸
Houston, Texas, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Primary Children's Medical Center
🇺🇸
Salt Lake City, Utah, United States
Feinstein Institute for Medical Rsearch
🇺🇸
New Hyde Park, New York, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Sainte-Justine Hospital
🇨🇦
Montreal, Quebec, Canada
Montefiore Medical Center
🇺🇸
Bronx, New York, United States