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

Kawasaki Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04078568
• Other study ID #: KD-3-01
• Status: Recruiting
• Phase: Phase 3
• Start date: January 15, 2020
• Est. completion date: September 2025

Study information

• Verified date: December 2023
• Source: Children's Hospital of Fudan University
• Contact: Fang Liu, MD.
• Phone: +86 021-64932800
• Email: liufang[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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) .

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3200
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month and older

Eligibility

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

Related Conditions & MeSH terms

• Kawasaki Disease
• Mucocutaneous Lymph Node Syndrome

Intervention

Drug:
• IVIG
IVIG at a single dose of 2 g/kg, with the maximum dose of 60g
• 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.
• Prednisolone
Intravenous methylprednisolone 1.6 mg/kg per day (given in 2 divided doses, with the maximum dose 60mg of prednisolone ) for 3 days, 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.

Locations

Country	Name	City	State
China	Beijing Children's Hospital	Beijing	Beijing
China	Children's Hospital, Capital Institute of Pediatrics	Beijing	Beijing
China	Bengbu First People's Hopital	Bengbu	Anhui
China	The First Hospital of Jilin University	Chang chun	Jilin
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	Chengdu Women's and Children's Central Hospital	Chengdu	Sichuan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Guangzhou Women and Children's Medical Center	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital	Guangzhou	Guangdong
China	Hangzhou First people's Hospital	Hangzhou	Zhejiang
China	Anhui Children's Hospital	Hefei	Anhui
China	Inner Mongolia People's Hospital	Hohhot	Inner Mongolia
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Kaifeng Children's Hospital	Kaifeng	Henan
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	Liuzhou Maternity and Children Healthcare Hospital	Liuzhou	Guangxi
China	Jiangxi Provincial Children's Hospital	Nanchang	Jiangxi
China	Children's Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Qingdao Women and Children's Hospital	Qingdao	Shandong
China	Qingdao Women and Children's Hospital (Liaoyang West Road)	Qingdao	Shandong
China	Children's Hospital of Fudan University	Shanghai	Shanghai
China	Shanghai Children's Hospital	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Shenzhen Children's Hospital	Shenzhen	Guangdong
China	Taihe Hospital Affiliated Hospital of Hubei University of Medicine	Shiyan	Hubei
China	Children's hospital of Soochow University	Suzhou	Jiangsu
China	Yuying Children's Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Union Hospital,Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Xi'an Children's Hospital	Xi'an	Shaanxi
China	Xuzhou Children's Hospital	Xuzhou	Jiangsu
China	Henan Children's Hospital	Zhengzhou	Henan
China	the First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	The Third Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (15)

Lead Sponsor

Collaborator

Children's Hospital of Fudan University

Beijing Children's Hospital, Chengdu Women's and Children's Central Hospital, Children's Hospital of Chongqing Medical University, Children's Hospital of Soochow University, First People's Hospital of Hangzhou, Inner Mongolia People's Hospital, Jiangxi Province Children's Hospital, Qilu Hospital of Shandong University, Shengjing Hospital, Sichuan Provincial People's Hospital, The First Hospital of Jilin University, Third Affiliated Hospital of Zhengzhou University, Wuhan Union Hospital, China, Yuying Children's Hospital of Wenzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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