Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease

November 12, 2014 updated by: Jane C. Burns, University of California, San Diego

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

196

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • University of California, San Diego
    • Ohio
      • Columbus, Ohio, United States
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 weeks to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Infliximab plus Intravenous immunoglobulin (IVIG)
Drug: Infliximab
5 mg/kg IV over 2 hours once
Other Names:
  • Remicade
Placebo Comparator: 2
Placebo plus IVIG
Drug: Placebo
Placebo (same volume as active drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Days of Fever Following Therapy During Study Period (up to 6 Weeks)
Time Frame: up to 6 weeks
up to 6 weeks
Change in C-reactive Protein (CRP) From Baseline at 24 Hours After Completion of Intravenous Immunoglobulin (IVIG) by Study Arm.
Time Frame: 24 hours
24 hours
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
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

Nationwide Children's Hospital

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

September 25, 2008

First Submitted That Met QC Criteria

September 25, 2008

First Posted (Estimate)

September 26, 2008

Study Record Updates

Last Update Posted (Estimate)

November 24, 2014

Last Update Submitted That Met QC Criteria

November 12, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01FD003514-01 (U.S. FDA Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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