Infliximab for Kawasaki Disease Patients Resistant to IVIG : a Multicentre, Prospective, Randomised Trial

Infliximab for Kawasaki Disease Patients Resistant to Intravenous Immunoglobulin : a Multicentre, Prospective, Randomised Trial

The objective of this study is to investigate the effect of infliximab to the children who don't respond to the first dose of intravenous immunoglobulin (IVIG) (2g/kg) in Kawasaki disease.

Study Overview

• Status: Completed
• Conditions: Kawasaki Disease
• Intervention / Treatment: Drug: Infliximab; Drug: IVIG

Detailed Description

Kawasaki disease(KD), the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease which is defined as a temperature of 38.0°C or higher at 36 hours to 7 days after completion of the infusion of intravenous immunoglobulin increases the risk of coronary artery lesions. We will conduct a multicenter, randomized, prospective trial to determine whether the use of infliximab to the children who don't respond to the first dose of IVIG(2g/kg) reduces the risk of coronary artery diseases. The IVIG-resistant children will be randomly assigned to either the infliximab or IVIG group in a 1:1 ratio and receive either infliximab (5 mg/kg at 1 mg/mL intravenously over 2 h) or IVIG (2g/kg). The level of leukocyte (WBC)counts, C-reactive protein, alanine transaminase,interleukin- 1( IL-1), interleukin- 6(IL-6), tumor necrosis factor-a(TNF-a), soluble tumor necrosis factor receptor-1(STNFR-I), soluble tumor necrosis factor receptor-2(STNFR-2), the fever days,and the cost of hospital stay will be analyzed between these two groups.The final outcome is the incidence of coronary artery lesions.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1)Individual patient's medical file data confirmed the diagnosis of KD using the 5th revised edition of diagnostic criteria for KD, issued by the Japan Kawasaki Disease Research Committee at the 7th International Kawasaki Disease Symposium in 2002.(2) Resistance to intravenous immunoglobulin in Kawasaki disease is defined as a temperature of 38.0°C or higher at 36 hours to 7 days after completion of the routine primary treatment .(3) the patients aged from 2 months to 12 years old. (4) All included patients required to sign an informed consent form

Exclusion Criteria:

. Exclusion criteria: (1) The patients with severe infections; (2) The patients with a history of tuberculosis or recent close contact with tuberculosis; (3) The patient vaccinated with live vaccine in 6 months; (4)The patients with the application of hormone or other immunosuppressive agents; (5) The patients didn"t want to signed informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Infliximab; For one group of patients with resistance to intravenous immunoglobulin in Kawasaki disease , we will give them infliximab (5mg/kg) once.	Drug: Infliximab; The treatment-resistant children will be randomly assigned to either the infliximab or IVIG group in a 1:1 ratio and receive either infliximab (5 mg/kg at 1 mg/mL intravenously over 2 h) or IVIG (2g/kg). The primary outcome measure is change in absolute cell counts, concentrations of C-reactive protein, alanine transaminase,IL-1,IL-6,TNF-a,STNFR-I,STNFR-2; number of fever days (24 h period with a temperature of at least 38•0°C) from enrolment; duration and cost of hospital stay.The secondary 0utcome Measure is the incidence of coronary artery abnormalities
ACTIVE_COMPARATOR: IVIG; For the other group of patients with resistance to intravenous immunoglobulin in Kawasaki disease , we will give them IVIG (2g/kg) once.	Drug: IVIG; The treatment-resistant children will be randomly assigned to either the infliximab or IVIG group in a 1:1 ratio and receive either infliximab (5 mg/kg at 1 mg/mL intravenously over 2 h) or IVIG (2g/kg). The primary outcome measure is change in absolute cell counts, concentrations of C-reactive protein, alanine transaminase,IL-1,IL-6,TNF-a,STNFR-I,STNFR-2; number of fever days (24 h period with a temperature of at least 38•0°C) from enrolment; duration and cost of hospital stay.The secondary 0utcome Measure is the incidence of coronary artery abnormalities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in concentrations of cytokines	we will obtain laboratory data including concentrations of C-reactive protein, alanine transaminase,IL-1,IL-6,TNF-a,STNFR-I,STNFR-2 at baseline, 72 h after completion of the intravenous immunoglobulin infusion, and at week 2 and week 4 after randomisation.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of coronary artery lesions(CAL)	Echocardiography is performed in the acute phase ,early and late recovery of Kawasaki disease	2 years

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Shanghai 10th People's Hospital; Shanghai Children's Medical Center; Shanghai 8th People's Hospital; Shanghai Xuhui Distrct Center Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (ESTIMATE): November 21, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): February 3, 2016
• Last Update Submitted That Met QC Criteria: February 2, 2016
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Kawasaki disease coronary artery lesion, IVIG- resistant, Infliximab
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Vasculitis; Skin Diseases, Vascular; Mucocutaneous Lymph Node Syndrome; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 2014-LF