Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease
Condition: Kawasaki Disease
MeSH terms: Mucocutaneous Lymph Node Syndrome
Intervention: Infliximab; Placebo
Intervention description: 5 mg/kg IV over 2 hours once; Placebo (same volume as active drug)
Intervention MeSH terms: Infliximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 196.0
Sex: All
Minimum age: 4 Weeks
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Kawasaki disease; Infliximab; Remicade; Pediatrics

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).
    

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