Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease
Information source: University of California, San Diego
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Kawasaki Disease
Intervention: Infliximab (Drug); Placebo (Drug)
Phase: Phase 3
Sponsored by: University of California, San Diego
Official(s) and/or principal investigator(s):
Jane C Burns, M.D., Principal Investigator, Affiliation: University of California, San Diego
Adriana H. Tremoulet, M.D., Study Director, Affiliation: University of California, San Diego
Octavio Ramilo, M.D., Study Director, Affiliation: University of Texas
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).
Official title: Infliximab (Remicade®) Plus Intravenous Immunoglobulin (IVIG) for the Primary Treatment of Patients With Acute Kawasaki Disease
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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
Number of Days of Fever Following Therapy During Study Period (up to 6 Weeks)
Change in C-reactive Protein (CRP) From Baseline at 24 Hours After Completion of Intravenous Immunoglobulin (IVIG) by Study Arm.
Change From Baseline in Left Anterior Descending Coronary Artery Outcomes at Week 2 by Treatment Arm
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.
Minimum age: N/A.
Maximum age: 17 Years.
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 â‰¥ 38. 3Â° 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 (â‰¥ 38. 3Â°C) for â‰¥ 3 days and 4/5 standard
clinical criteria (Table 1)
- Case definition for incomplete KD: Fever â‰¥ 5 days and 2-3 clinical criteria plus
either C-reactive protein (CRP) â‰¥ 3. 0 mg/dL or ESR â‰¥40 mm/hr AND â‰¥ 3
supplemental laboratory criteria: albumin â‰¤ 3. 0 g/dl, anemia for age, ALT â‰¥ 45,
platelet count â‰¥ 450,000/mm3, white blood cell count â‰¥ 15,000/mm3, or
urinalysis with â‰¥10 white blood cells/hpf.
- Case definition for incomplete KD with echocardiogram data: Fever â‰¥ 5 days and
<4/5 clinical criteria plus abnormal echocardiogram with z score of LAD or RCA â‰¥
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.
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 (KineretÂ®), etanercept (EnbrelÂ®), or adalimumab (HumiraÂ®)
within 1 month prior to first study drug administration.
6. Have any chronic disease, except asthma, atopic dermatitis or controlled seizure
7. Have documented history of current active Hepatitis B or a history of Hepatitis C
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
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
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 â‰¥ 48 hours
Locations and Contacts
University of California, San Diego, La Jolla, California 92093, United States
Nationwide Children's Hospital, Columbus, Ohio, United States
Kawasaki Disease Research Center at UCSD
Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, Melish ME, Jackson MA, Asmar BI, Lang DJ, Connor JD, Capparelli EV, Keen ML, Mamun K, Keenan GF, Ramilo O. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2008 Dec;153(6):833-8. doi: 10.1016/j.jpeds.2008.06.011. Epub 2008 Jul 30.
Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008 Jul;153(1):117-21. doi: 10.1016/j.jpeds.2007.12.021. Epub 2008 Mar 4.
Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, Atz AM, Li JS, Takahashi M, Baker AL, Colan SD, Mitchell PD, Klein GL, Sundel RP; Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007 Feb 15;356(7):663-75.
Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004 Dec;114(6):1708-33. Erratum in: Pediatrics. 2005 Apr;115(4):1118.
Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, Balfour I, Shen CA, Michel ED, Shulman ST, Melish ME. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005 May;146(5):662-7.
Starting date: March 2009
Last updated: November 12, 2014