Clinical trial NCT00841789: A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease
Official title: A Randomized, Double Blind, Placebo Controlled Study of the Effects of Etanercept in Children Presenting With Kawasaki Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mucocutaneous Lymph Node Syndrome
Kawasaki Disease
Keywords: Etanercept
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2009-02-11
Enrollment: 205
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: IVIG Refractory
timeFrame: 42 days after initial dose
Secondary outcomes:
measure: 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
timeFrame: 42 days after initial dose
Other outcomes:
measure: Change in Coronary Artery Dimension by z Score Compared With General Estimating Equation
timeFrame: 6 weeks
measure: Overall Change in z Score Over Time in Patients With Dilated Coronary Artery at Baseline Within Patients.
timeFrame: 6 weeks
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Feinstein Institute for Medical Rsearch
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Montreal
country: Canada
facility: Sainte-Justine Hospital
state: Quebec
Study officials:
affiliation: Seattle Children's Hospital
name: Michael A Portman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Portman MA, Olson A, Soriano B, Dahdah N, Williams R, Kirkpatrick E. Etanercept as adjunctive treatment for acute Kawasaki disease: study design and rationale. Am Heart J. 2011 Mar;161(3):494-9. doi: 10.1016/j.ahj.2010.12.003.
citation: Portman MA, Dahdah NS, Slee A, Olson AK, Choueiter NF, Soriano BD, Buddhe S, Altman CA; EATAK Investigators. Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial. Pediatrics. 2019 Jun;143(6):e20183675. doi: 10.1542/peds.2018-3675. Epub 2019 May 2.
citation: Sagiv E, Slee A, Buffone A, Choueiter NF, Dahdah NS, Portman MA. Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial. Cardiol Young. 2023 Apr;33(4):613-618. doi: 10.1017/S1047951122001470. Epub 2022 May 12.