Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease
NCT ID: NCT00760435
Last Updated: 2014-11-24
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
196 participants
INTERVENTIONAL
2009-03-31
2012-10-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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1
Infliximab plus Intravenous immunoglobulin (IVIG)
Infliximab
5 mg/kg IV over 2 hours once
2
Placebo plus IVIG
Placebo
Placebo (same volume as active drug)
Interventions
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Infliximab
5 mg/kg IV over 2 hours once
Placebo
Placebo (same volume as active drug)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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
4 Weeks
17 Years
ALL
No
Sponsors
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Nationwide Children's Hospital
OTHER
University of California, San Diego
OTHER
Responsible Party
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Jane C. Burns
Professor
Principal Investigators
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Jane C Burns, M.D.
Role: PRINCIPAL_INVESTIGATOR
University of California, San Diego
Adriana H. Tremoulet, M.D.
Role: STUDY_DIRECTOR
University of California, San Diego
Octavio Ramilo, M.D.
Role: STUDY_DIRECTOR
University of Texas
Locations
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University of California, San Diego
La Jolla, California, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Countries
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References
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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. doi: 10.1056/NEJMoa061235.
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. doi: 10.1542/peds.2004-2182.
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. doi: 10.1016/j.jpeds.2004.12.022.
Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, Kanegaye JT, Kovalchin JP, Printz BF, Ramilo O, Burns JC. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet. 2014 May 17;383(9930):1731-8. doi: 10.1016/S0140-6736(13)62298-9. Epub 2014 Feb 24.
Burns JC, Song Y, Bujold M, Shimizu C, Kanegaye JT, Tremoulet AH, Franco A. Immune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin. Clin Exp Immunol. 2013 Dec;174(3):337-44. doi: 10.1111/cei.12182.
Kanegaye JT, Van Cott E, Tremoulet AH, Salgado A, Shimizu C, Kruk P, Hauschildt J, Sun X, Jain S, Burns JC. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013 Jun;162(6):1259-63, 1263.e1-2. doi: 10.1016/j.jpeds.2012.11.064. Epub 2013 Jan 7.
Other Identifiers
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