Different Doses of IVIG for Kawasaki Disease

Different Doses of IVIG for Kawasaki Disease: a Multicentre, Prospective, Randomised Trial

The objective of this study is to investigate the effect of different doses of intravenous immunoglobulin (IVIG) (1g/kg once, 1g/kg twice, 2g/kg once) for Kawasaki disease (KD) in a multicentre, prospective,randomised trial.

Study Overview

• Status: Completed
• Conditions: Kawasaki Disease
• Intervention / Treatment: Drug: IVIG (1g/kg,once); Drug: IVIG (1g/kg,twice); Drug: IVIG (2g/kg.once)

Detailed Description

Kawasaki disease is an acute febrile illness recognized most often in young children. Coronary abnormality is the most serious complication preventable with intravenous immunoglobulin (IVIG) administration. Various treatment regimens of IVIG have been reported.The optimal administrative doses of IVIG deserves more observations.We will conduct a multicenter, randomized, prospective trial to determine the effect of different doses of IVIG (1g/kg once, 1g/kg twice, 2g/kg once) for Kawasaki disease. The KD children will be randomly assigned to three groups and were given different IVIG regimen (1g/kg once, 1g/kg twice, 2g/kg once)as initial treatment. Patient age, gender, white blood cell count, hemoglobin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), red blood cell specific volume (HCT) , serum albumin, the fever days,and the cost of hospital stay will be analyzed among the three groups. The primary outcome is the duration of fever subsided and the incidence of coronary artery lesions .

• Study Type: Interventional
• Enrollment (Actual): 404
• 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: 1 month to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.
• the patients aged from 1 months to 12 years old.
• All included patients required to sign an informed consent form.
• the patients didn't receive treatment before.

Exclusion Criteria:

• The patients with the application of hormone or other immunosuppressive agents;
• 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 Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IVIG(1g/kg,once); The KD children will be randomly assigned to three groups. The patients in group C will receive IVIG 1g/kg once.	Drug: IVIG (1g/kg,once); Group C patients received IVIG 1g/kg per day once. The IVIG was started on the fifth to tenth day of illness. In combination with IVIG, the patients were administered aspirin at a dose of 30 mg/kg per day; this dose was reduced to 3-5 mg/kg per day after the fever disappeared for 3 days and the CRP value was ≤8mg/L. Patients who were admitted before the fourth day of illness were treated only with aspirin. Each immunoglobulin was administered at a dose of 1 g/kg for 10h. Patients who did not respond to initial IVIG therapy were given a second dose of IVIG 24-36 hours after the initial dose at 2g/kg. Patients who did not respond to second dose IVIG were given methylprednisolone 10mg/kg for 3 days or infliximab 5mg/kg once.; Other Names: Asprin
Experimental: IVIG(1g/kg,twice); The KD children will be randomly assigned to three groups. The patients in group B will receive IVIG 1g/kg for 2 days continuousl.	Drug: IVIG (1g/kg,twice); Group B patients received IVIG 1g/kg for 2 days continuously. The IVIG was started on the fifth to tenth day of illness. In combination with IVIG, the patients were administered aspirin at a dose of 30 mg/kg per day; this dose was reduced to 3-5 mg/kg per day after the fever disappeared for 3 days and the CRP value was ≤8mg/L. Patients who were admitted before the fourth day of illness were treated only with aspirin. Each immunoglobulin was administered at a dose of 1 g/kg for 10h. Patients who did not respond to initial IVIG therapy were given a second dose of IVIG 24-36 hours after the initial dose at 2g/kg. Patients who did not respond to second dose IVIG were given methylprednisolone 10mg/kg for 3 days or infliximab 5mg/kg once.; Other Names: Asprin
Active Comparator: IVIG(2g/kg.once); The KD children will be randomly assigned to three groups. The patients in group A will receive IVIG 2g/kg once.	Drug: IVIG (2g/kg.once); Group A patients received IVIG 2g/kg per day once. The IVIG was started on the fifth to tenth day of illness. In combination with IVIG, the patients were administered aspirin at a dose of 30 mg/kg per day; this dose was reduced to 3-5 mg/kg per day after the fever disappeared for 3 days and the CRP value was ≤8mg/L. Patients who were admitted before the fourth day of illness were treated only with aspirin. Each immunoglobulin was administered at a dose of 1 g/kg for 10h. Patients who did not respond to initial IVIG therapy were given a second dose of IVIG 24-36 hours after the initial dose at 2g/kg. Patients who did not respond to second dose IVIG were given methylprednisolone 10mg/kg for 3 days or infliximab 5mg/kg once.; Other Names: Asprin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of fever subsided to normal after initial IVIG finished	Hours of fever subsided to normal after initial IVIG finished	36 hours after IVIG finished
incidence of coronary artery lesions(CAL) after IVIG finished	incidence of coronary artery lesions(CAL) after IVIG finished diagnosed by echocardiography	start from IVIG finished, ended by the end of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of coronary artery lesions(CAL) after IVIG finished	incidence of coronary artery lesions(CAL) after IVIG finished diagnosed by echocardiography	start from IVIG finished, ended by the end of 1 month
incidence of coronary artery lesions(CAL) after IVIG finished	incidence of coronary artery lesions(CAL) after IVIG finished diagnosed by echocardiography	start from IVIG finished, ended by the end of 3 month
incidence of coronary artery lesions(CAL) after IVIG finished	incidence of coronary artery lesions(CAL) after IVIG finished diagnosed by echocardiography and coronary atery angiogram	start from IVIG finished, ended by the end of 6 month
Total dose of immunoglobin used for every patient	Total dose of immunoglobin used for every patient	estimated about up to 10 days, start from admission,ended by discharge
total medical cost for KD treatment during hospital stay	record the hospital duration of every patient and the medical expenses for KD	estimated about up to 10 days, start from admission,ended by discharge
total frequency (%) of severe adverse events	Severe adverse events included death, infection or exacerbation, heart failure, allergic reaction, etc	estimated about up to 10 days, start from admission,ended by discharge

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: Shanghai Children's Hospital; Shanghai Children's Medical Center
• Investigators: Study Chair: Guoying Huang, PHD, Children Hospital of Fudan University

Publications and helpful links

General Publications

• He L, Liu F, Yan W, Huang M, Huang M, Xie L, Guo Y, Xu X, Chu C, Wu L, Liang X, Sun S, Wang F, Zhao L, Zhao Q, Ma X, Xie L, Huang G. Randomized trial of different initial intravenous immunoglobulin regimens in Kawasaki disease. Pediatr Int. 2021 Jul;63(7):757-763. doi: 10.1111/ped.14656. Epub 2021 Jun 16.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: May 7, 2015
• First Submitted That Met QC Criteria: May 8, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 8, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Kawasaki disease IVIG
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Vasculitis; Skin Diseases, Vascular; Mucocutaneous Lymph Node Syndrome; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: KD(2015-2016)