Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease

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Brief Title

Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease

Official Title

Infliximab (Remicade®) Plus Intravenous Immunoglobulin (IVIG) for the Primary Treatment of Patients With Acute Kawasaki Disease

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).
    

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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

The Number of Subjects in Each Arm That Have Persistent or Recrudescent Fever 24 Hours After Completion of the Intravenous Immunoglobulin (IVIG) Infusion

Secondary Outcome

 Number of Days of Fever Following Therapy During Study Period (up to 6 Weeks)

Condition

Kawasaki Disease

Intervention

Infliximab

Study Arms / Comparison Groups

 1
Description:  Infliximab plus Intravenous immunoglobulin (IVIG)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

196

Start Date

March 2009

Completion Date

October 2012

Primary Completion Date

October 2012

Eligibility Criteria

        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
      

Gender

All

Ages

N/A - 17 Years

Accepts Healthy Volunteers

No

Contacts

Jane C Burns, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00760435

Organization ID

1R01FD003514-01


Responsible Party

Principal Investigator

Study Sponsor

University of California, San Diego

Collaborators

 Nationwide Children's Hospital

Study Sponsor

Jane C Burns, M.D., Principal Investigator, University of California, San Diego


Verification Date

November 2014