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Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease

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ClinicalTrials.gov Identifier: NCT00760435
Recruitment Status : Completed
First Posted : September 26, 2008
Results First Posted : November 13, 2014
Last Update Posted : November 24, 2014
Nationwide Children's Hospital
Information provided by (Responsible Party):
Jane C. Burns, University of California, San Diego

Brief Summary:
The purpose of this study is to determine whether the addition of infliximab to standard primary therapy of intravenous immunoglobulin (IVIG) and high dose aspirin will reduce resistance to therapy in acute Kawasaki disease (KD).

Condition or disease Intervention/treatment Phase
Kawasaki Disease Drug: Infliximab Drug: Placebo Phase 3

Detailed Description:
KD, an orphan disease of low prevalence in U.S. children, causes significant long term cardiac sequelae in a subset of patients. KD patients that are resistant to therapy are more likely to develop coronary artery abnormalities. This phase III placebo-controlled, multicenter, randomized clinical trial of infliximab plus standard therapy vs. placebo plus standard therapy in acute KD will determine if the addition of infliximab to primary therapy can reduce the percentage of children resistant to therapy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 196 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Infliximab (Remicade®) Plus Intravenous Immunoglobulin (IVIG) for the Primary Treatment of Patients With Acute Kawasaki Disease
Study Start Date : March 2009
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Arm Intervention/treatment
Experimental: 1
Infliximab plus Intravenous immunoglobulin (IVIG)
Drug: Infliximab
5 mg/kg IV over 2 hours once
Other Name: Remicade

Placebo Comparator: 2
Placebo plus IVIG
Drug: Placebo
Placebo (same volume as active drug)

Primary Outcome Measures :
  1. The Number of Subjects in Each Arm That Have Persistent or Recrudescent Fever 24 Hours After Completion of the Intravenous Immunoglobulin (IVIG) Infusion [ Time Frame: 10 weeks ]

Secondary Outcome Measures :
  1. Number of Days of Fever Following Therapy During Study Period (up to 6 Weeks) [ Time Frame: up to 6 weeks ]
  2. Change in C-reactive Protein (CRP) From Baseline at 24 Hours After Completion of Intravenous Immunoglobulin (IVIG) by Study Arm. [ Time Frame: 24 hours ]
  3. Change From Baseline in Left Anterior Descending Coronary Artery Outcomes at Week 2 by Treatment Arm [ Time Frame: 2 weeks ]
    left anterior descending coronary artery Z-score; a Z score is the coronary artery adjusted for body surface area

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Weeks to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. All eligible subjects, or legal representative, must provide written informed consent/assent, prior to initiation of any study procedure.
  2. Eligible subjects will be infants and children, 4 weeks to 17 years old, who have had fever for 3 to 15 days (illness day 1 = first day of fever ≥ 38.3° C)
  3. Patients who meet one of the following sets of criteria will be eligible for enrollment (adapted from AHA guidelines: Newburger et al. 2004):

    • Case definition for complete KD: Fever (≥ 38.3°C) for ≥ 3 days and 4/5 standard clinical criteria (Table 1)
    • Case definition for incomplete KD: Fever ≥ 5 days and 2-3 clinical criteria plus either C-reactive protein (CRP) ≥ 3.0 mg/dL or ESR ≥40 mm/hr AND ≥ 3 supplemental laboratory criteria: albumin ≤ 3.0 g/dl, anemia for age, ALT ≥ 45, platelet count ≥ 450,000/mm3, white blood cell count ≥ 15,000/mm3, or urinalysis with ≥10 white blood cells/hpf.
    • Case definition for incomplete KD with echocardiogram data: Fever ≥ 5 days and <4/5 clinical criteria plus abnormal echocardiogram with z score of LAD or RCA ≥ 2.5
  4. Females of childbearing potential and males must be using adequate contraception (abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the trial.
  5. All eligible subjects must have a chest radiograph within one week prior to first infusion of study drug with no evidence of tuberculosis or other infection.

Exclusion Criteria:

  1. Have been receiving corticosteroids (i.e. via any route) at doses > 1 mg/kg prednisone equivalent daily.
  2. History of tuberculosis (TB) or TB exposure.
  3. Have received a BCG vaccination within the past 6 months.
  4. History of histoplasmosis or coccidioidomycosis
  5. Have received anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 1 month prior to first study drug administration.
  6. Have any chronic disease, except asthma, atopic dermatitis or controlled seizure disorder.
  7. Have documented history of current active Hepatitis B or a history of Hepatitis C infection.
  8. Have a documented history of human immunodeficiency virus (HIV) infection.
  9. Have received a transplanted organ (with the exception of a corneal transplant performed > 3 months prior to the first study drug administration).
  10. Have a known malignancy or history of malignancy within the 5-year period prior to first study drug administration (with the exception of basal cell or squamous cell carcinoma of the skin that has been completely excised without evidence of recurrence).
  11. Have a history of prior lymphoproliferative disease including lymphoma.
  12. Have multiple sclerosis or other central demyelinating disorder.
  13. Have received any previous treatment with infliximab or other monoclonal antibodies
  14. Have used any investigational drug within 1 month prior to first study drug administration or within 5 half-lives of the investigational agent, whichever is longer.
  15. Are participating in another investigative trial, involving investigational agents, during participation in this trial.
  16. Have a history of substance abuse (drug or alcohol) within the previous 3 years.
  17. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.
  18. Have a known allergy to murine proteins or other chimeric proteins.
  19. Patients with ischemic congestive heart failure, defined by ECG changes, elevated Troponin 1 and CPK-MB consistent with myocardial ischemia.
  20. Have an abnormal chest radiograph
  21. Afebrile for ≥ 48 hours

Information from the National Library of Medicine

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): NCT00760435

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United States, California
University of California, San Diego
La Jolla, California, United States, 92093
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States
Sponsors and Collaborators
University of California, San Diego
Nationwide Children's Hospital
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Principal Investigator: Jane C Burns, M.D. University of California, San Diego
Study Director: Adriana H. Tremoulet, M.D. University of California, San Diego
Study Director: Octavio Ramilo, M.D. University of Texas
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jane C. Burns, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00760435    
Other Study ID Numbers: 1R01FD003514-01 ( U.S. FDA Grant/Contract )
First Posted: September 26, 2008    Key Record Dates
Results First Posted: November 13, 2014
Last Update Posted: November 24, 2014
Last Verified: November 2014
Keywords provided by Jane C. Burns, University of California, San Diego:
Kawasaki disease
Additional relevant MeSH terms:
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Mucocutaneous Lymph Node Syndrome
Vascular Diseases
Cardiovascular Diseases
Lymphatic Diseases
Skin Diseases, Vascular
Skin Diseases
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents