Efficacy of Immunoglobulin Plus Prednisolone in Reducing Coronary Artery Lesion in Patients With Kawasaki Disease

Efficacy of Immunoglobulin Plus Prednisolone in Reducing Coronary Artery Lesion in Patients With Kawasaki Disease: A Multicentre Randomised Controlled Trial

This study evaluates the efficacy of the addition of prednisolone to conventional initial treatment (intravenous immunoglobulin [IVIG] plus aspirin) in reducing coronary artery lesion in children with Kawasaki disease (KD) .

Study Overview

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

Detailed Description

This is a multicenter, open-label, blind-endpoints, randomized controlled trial at more than 10 hospitals in China. The investigators enrolled KD children diagnosed within 10 days of onset. Participants will be randomly assigned in a 1:1 ratio to the control group (receiving 2g/kg IVIG and 30 mg/kg aspirin) or the intervention group (receiving 2 g/kg IVIG, 30 mg/kg aspirin and additional 2 mg/kg prednisolone). Baseline characteristics of each participant will be collected, including sex, age of onset, height, body weight, subtype of KD, fever days before initial IVIG, echocardiographic findings at enrolment, and a series of pre-IVIG laboratory tests. Two-dimensional echocardiography will be performed at admission, 2 weeks, 1 month, 3 months, 6 months，and 12 months after onset of KD to assess the coronary artery lesions.

• Study Type: Interventional
• Enrollment (Actual): 3208
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • Bengbu First People's Hopital
    • Hefei, Anhui, China, 230022
      • Anhui Children's Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100020
      • Children's Hospital, Capital Institute of Pediatrics
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400014
      • Children's Hospital of Chongqing Medical University
  • Fujian
    • Xiamen, Fujian, China, 361006
      • Xiamen Children's Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510623
      • Guangzhou Women and Children's Medical Center
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital
    • Shenzhen, Guangdong, China, 518038
      • Shenzhen Children's Hospital
  • Guangxi
    • Liuchow, Guangxi, China, 545001
      • Liuzhou Maternity and Children Healthcare Hospital
  • Henan
    • Kaifeng, Henan, China, 475000
      • Kaifeng Children's Hospital
    • Zhengzhou, Henan, China, 450052
      • the First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450052
      • The Third Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450018
      • Henan Children's Hospital
  • Hubei
    • Shiyan, Hubei, China, 442000
      • Taihe Hospital Affiliated Hospital of Hubei University of Medicine
    • Wuhan, Hubei, China, 430022
      • Union Hospital,Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410002
      • Hunan Provincial People's Hospital
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 010017
      • Inner Mongolia People's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Children's Hospital of Nanjing Medical University
    • Suzhou, Jiangsu, China, 215003
      • Children's Hospital of Soochow University
    • Xuzhou, Jiangsu, China, 221006
      • Xuzhou Children's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial Children's Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710003
      • Xi'an Children's Hospital
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
    • Qingdao, Shandong, China, 266011
      • Qingdao Women and Children's Hospital (Liaoyang West Road)
    • Qingdao, Shandong, China, 266011
      • Qingdao Women and Children's Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University
    • Shanghai, Shanghai Municipality, China, 200040
      • Shanghai Children's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
    • Chengdu, Sichuan, China, 610074
      • Chengdu Women's and Children's Central Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Hangzhou First People's Hospital
    • Wenzhou, Zhejiang, China, 325027
      • Yuying Children's Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meeting diagnostic criteria for Kawasaki disease (KD) released by American Heart Association (AHA) in 2017
• Diagnosed before the tenth day of illness (with the first day of illness defined as the first day of fever)
• Not treated with IVIG yet
• Age ≥1 month

Exclusion Criteria:

• Z score of any coronary artery before initial treatment ≥10
• Receiving steroids or other immunosuppressive agents in the previous 30 days
• With a previous history of KD
• Afebrile before enrolment
• With suspected infectious diseases including sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella and influenza
• With serious immune diseases such as immunodeficiency or chromosomal abnormalities

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: the standard group; IVIG 2g/kg once, given within 12 to 24 hours;; Aspirin 30 mg/kg in oral per day (given in 3 divided doses), then 3 to 5 mg/kg per day when fever subsides for 3 days and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.	Drug: IVIG; IVIG at a single dose of 2 g/kg, with the maximum dose of 60g; Other Names: Intravenous Immunoglobulins, Human; Drug: Aspirin; Aspirin 30 mg/kg in oral per day (given in 3 divided doses), then 3 to 5 mg/kg per day when fever subsides for 3 days and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.; Other Names: Acetylsalicylic acid
Experimental: the standard+prednisolone group; IVIG 2g/kg once, given within 12 to 24 hours;; Aspirin 30 mg/kg in oral per day (given in 3 divided doses), then 3 to 5 mg/kg per day when fever subsides for 3 days and CRP is normal. Aspirin will be continued for at least 6 weeks after onset of illness.; Intravenous methylprednisolone 1.6 mg/kg per day (given in 2 divided doses) for 3 days, which is administered concurrently with the initial IVIG infusion and completed within 30-60 minutes, then changed to oral prednisolone 2 mg/kg when fever subsides for 3 days . If CRP is normal, the oral dose will be reduced every 5 days from 2 mg/kg to 1 mg/kg to 0.5 mg/kg (tapered over 15 days). Then prednisolone will be discontinued.	Drug: IVIG; IVIG at a single dose of 2 g/kg, with the maximum dose of 60g; Other Names: Intravenous Immunoglobulins, Human; Drug: Aspirin; Aspirin 30 mg/kg in oral per day (given in 3 divided doses), then 3 to 5 mg/kg per day when fever subsides for 3 days and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.; Other Names: Acetylsalicylic acid; Drug: Prednisolone; Intravenous methylprednisolone 1.6 mg/kg per day (given in 2 divided doses, with the maximum dose 60mg of prednisolone ) for 3 days, which is administered concurrently with the initial IVIG infusion and completed within 30-60 minutes, then changed to oral prednisolone 2 mg/kg when fever subsides for 3 days. If CRP is normal, the oral dose will be reduced every 5 days from 2 mg/kg to 1 mg/kg to 0.5 mg/kg (tapered over 15 days). Then prednisolone will be discontinued.; Other Names: STEROLONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of coronary artery lesions(CAL) at one month of illness	Two-dimensional echocardiography will be performed to evaluate CAL at 1 month of illness. The measurement of each patient included the diameter of the left main coronary artery (LMCA), the left anterior descending artery (LAD), the left circumflex coronary artery (LCX), and the proximal and middle segments of the right coronary artery (RCA). Z score of each coronary artery will be calculated（Journal of the American Society of Echocardiography, 2011, 24(1).）. CAL is defined as z≥2of any coronary artery of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.	at one month of illness

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of the need for additional treatment	Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization. Participants who have recurrent or persistent fever (axillary temperature ≥37.5°C or rectal temperature ≥38°C) after 36 hours of completion of initial IVIG infusion will be given additional treatment.	from admission to discharge (about 2 weeks of illness)
Duration of fever (hours) after initiation of initial IVIG infusion	Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization. Participants with an axillary temperature <37.5℃ (or rectal temperature <38℃) for more than 24 hours are considered afebrile. Record the time of the initiation of IVIG infusion and the time of the body temperature first becoming normal.	from initiation of initial IVIG infusion to the first record of being afebrile(defined as an axillary temperature <37.5 for more than 24 hours)
Changes in z scores of LMCA throughout the study period	This is a repeated measurement. The internal diameter of LMCA will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）.	from admission to 12 months of illness
Changes in z scores of LAD throughout the study period	This is a repeated measurement. The internal diameter of LAD will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）.	from admission to 12 months of illness
Changes in z scores of LCX throughout the study period	This is a repeated measurement. The internal diameter of LCX will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）.	from admission to 12 months of illness
Changes in z scores of the proximal segment of RCA throughout the study period	This is a repeated measurement. The internal diameter of the proximal segment of RCA will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）.	from admission to 12 months of illness
Changes in z scores of the middle segment of RCA throughout the study period	This is a repeated measurement. The internal diameter of the middle segment of RCA will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）.	from admission to 12 months of illness
Change in serum C-reactive protein (CRP) concentration	CRP level is measured before initial IVIG infusion and 72 hours after completion of initial IVIG infusion.	from admission to 72 hours after completion of initial IVIG infusion
Number of patients with serious adverse events	This is a composite outcome, including death, hypertension, severe infection, allergic reactions, heart failure, thrombosis, etc.	from admission to 3 months of illness
Occurrence of medium-to-giant coronary artery aneurysms (CAAs)	Exploratory Outcome. This is a repeatedly measured binary variable. CAL classification is based on the maximum z score according to the 2017 American Heart Association guideline. Medium CAA is defined as a maximum Z score ≥5 to <10, and all internal diameters <8 mm; large or giant CAA is defined as a maximum Z score ≥10, or any internal diameter ≥8 mm. Data were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset
Occurrence of large/giant CAAs	Exploratory Outcome. This is a repeatedly measured binary variable. CAL classification is based on the maximum z score according to the 2017 American Heart Association guideline. Medium CAA is defined as a maximum Z score ≥5 to <10, and all internal diameters <8 mm; large or giant CAA is defined as a maximum Z score ≥10, or any internal diameter ≥8 mm. Data were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset
Occurrence of CAL progression within 3 months of illness onset	Exploratory outcome. CAL progression is defined as an increment in the Z score ≥1 from admission in any coronary artery (LMCA, LAD, LCX, proximal and middle segments of RCA) at any given time point within 3 months of illness onset. The outcome was assessed in all participants and those with CAL at baseline.	from admission to 3 months of illness onset
Changes in absolute diameter of LMCA throughout the study period	Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of LMCA were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset
Changes in absolute diameter of LAD throughout the study period	Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of LAD were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset
Changes in absolute diameter of LCX throughout the study period	Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of LCX were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset
Changes in absolute diameter of the proximal segment of RCA throughout the study period	Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of the proximal segment of RCA were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset
Changes in absolute diameter of the middle segment of RCA throughout the study period	Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of the middle segment of RCA were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively.	from admission to 12 months of illness onset

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: First People's Hospital of Hangzhou; Qilu Hospital of Shandong University; Shengjing Hospital; The First Hospital of Jilin University; Beijing Children's Hospital; Children's Hospital of Soochow University; Chengdu Women's and Children's Central Hospital; Sichuan Provincial People's Hospital; Inner Mongolia People's Hospital; Jiangxi Province Children's Hospital; Yuying Children's Hospital of Wenzhou Medical University; Children's Hospital of Chongqing Medical University; Third Affiliated Hospital of Zhengzhou University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Investigators: Study Director: Fang Liu, MD., Children's Hospital of Fudan University

Publications and helpful links

General Publications

• Lin SY, He L, Xie LP, Wang Y, Lin YX, Cao YY, Yan WL, Liu F, Huang GY. Effects of immunoglobulin plus prednisolone in reducing coronary artery lesions in patients with Kawasaki disease: study protocol for a phase III multicenter, open-label, blinded-endpoints randomized controlled trial. Trials. 2021 Dec 11;22(1):898. doi: 10.1186/s13063-021-05807-3.
• Lin S, He Y, He L, Liu Y, Wang F, Xiong Z, Lin Y, Ye L, Chu C, Wang F, Zhao L, Cao Y, Zheng Y, Huang Q, Wang J, Liang X, Zhao Q, Sun S, Dou Y, He W, Huang X, Sun J, Huang X, Li Y, Liao Y, Lv H, Pan S, Zhu H, An X, He X, Zhao C, Liu X, Hu Y, Piao J, Qin L, Dong X, Peng Q, Wang C, Lin S, Huang P, Wu R, Peng H, Li Z, Wang D, Liu X, Yan W, Liu F, Huang G; Chinese Kawasaki Disease Collaboration Network. Randomized Trial of Adjunctive Prednisolone for Kawasaki Disease. N Engl J Med. 2026 Apr 16;394(15):1480-1490. doi: 10.1056/NEJMoa2511478.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): December 30, 2024
• Study Completion (Actual): November 6, 2025

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: prednisolone; Kawasaki disease; coronary artery lesion
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Skin Diseases; Lymphatic Diseases; Skin Diseases, Vascular; Vasculitis; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Mucocutaneous Lymph Node Syndrome; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phenols; Benzene Derivatives; Pregnadienetriols; Immunoglobulin Isotypes; Immunoglobulin G; Salicylates; Hydroxybenzoates; Aspirin; Prednisolone; Immunoglobulins, Intravenous
• Other Study ID Numbers: KD-3-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No