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

Primary Purpose

Kawasaki Disease

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

IVIG

Aspirin

Prednisolone

About this trial

This is an interventional treatment trial for Kawasaki Disease focused on measuring Kawasaki disease, prednisolone, coronary artery lesion

Eligibility Criteria

1 Month - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Beijing Children's HospitalRecruiting
The First Hospital of Jilin UniversityRecruiting
Sichuan Provincial People's HospitalRecruiting
Chengdu Women's and Children's Central HospitalRecruiting
Children's Hospital of Chongqing Medical UniversityRecruiting
Hangzhou First people's HospitalRecruiting
Inner Mongolia People's HospitalRecruiting
Qilu Hospital of Shandong UniversityRecruiting
Jiangxi Provincial Children's HospitalRecruiting
Children's Hospital of Fudan UniversityRecruiting
Shengjing Hospital of China Medical UniversityRecruiting
Children's hospital of Soochow University
Yuying Children's Hospital of Wenzhou Medical University
Union Hospital,Tongji Medical College of Huazhong University of Science and TechnologyRecruiting
The Third Affiliated Hospital of ZhengzhouUniversity

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

the standard group

the standard+prednisolone group

Arm Description

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.

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, 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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).）.

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).）.

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).）.

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).）.

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).）.

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.

Number of patients with serious adverse events

This is a composite outcome, including death, hypertension, severe infection, allergic reactions, heart failure, thrombosis, etc.

Full Information

NCT ID

NCT04078568

First Posted

August 16, 2018

Last Updated

September 27, 2023

Sponsor

Children's Hospital of Fudan University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04078568

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 15, 2020 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Children's Hospital of Fudan University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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) .

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Kawasaki Disease

Keywords

Kawasaki disease, prednisolone, coronary artery lesion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Masking Description

Participants and physicians will not be masked to the assignment. Pediatric cardiologists who assess coronary artery lesions (CAL) by echocardiography will be masked to the allocation.

Allocation

Randomized

Enrollment

3200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

the standard group

Arm Type

Active Comparator

Arm Description

Arm Title

the standard+prednisolone group

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

IVIG

Other Intervention Name(s)

Intravenous Immunoglobulins, Human

Intervention Description

IVIG at a single dose of 2 g/kg, with the maximum dose of 60g

Intervention Type

Drug

Intervention Name(s)

Aspirin

Other Intervention Name(s)

Acetylsalicylic acid

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Prednisolone

Other Intervention Name(s)

STEROLONE

Intervention Description

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.

Primary Outcome Measure Information:

Title

Percentage of coronary artery lesions(CAL) at one month of illness

Description

Time Frame

at one month of illness

Secondary Outcome Measure Information:

Title

Percentage of the need for additional treatment

Description

Time Frame

from admission to discharge (about 2 weeks of illness)

Title

Duration of fever (hours) after initiation of initial IVIG infusion

Description

Time Frame

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)

Title

Changes in z scores of LMCA throughout the study period

Description

Time Frame

from admission to 12 months of illness

Title

Changes in z scores of LAD throughout the study period

Description

Time Frame

from admission to 12 months of illness

Title

Changes in z scores of LCX throughout the study period

Description

Time Frame

from admission to 12 months of illness

Title

Changes in z scores of the proximal segment of RCA throughout the study period

Description

Time Frame

from admission to 12 months of illness

Title

Changes in z scores of the middle segment of RCA throughout the study period

Description

Time Frame

from admission to 12 months of illness

Title

Change in serum C-reactive protein (CRP) concentration

Description

CRP level is measured before initial IVIG infusion and 72 hours after completion of initial IVIG infusion.

Time Frame

from admission to 72 hours after completion of initial IVIG infusion

Title

Number of patients with serious adverse events

Description

This is a composite outcome, including death, hypertension, severe infection, allergic reactions, heart failure, thrombosis, etc.

Time Frame

from admission to 3 months of illness

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Month

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fang Liu, MD.

Phone

+86 021-64932800

liufang@fudan.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Lan He, MD.

Phone

+8602164932026

helan0361@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fang Liu, MD.

Organizational Affiliation

Children's Hospital of Fudan University

Official's Role

Study Director

Facility Information:

Facility Name

Beijing Children's Hospital

City

Beijing

ZIP/Postal Code

100045

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qirui Li, MD

Facility Name

The First Hospital of Jilin University

City

Chang chun

ZIP/Postal Code

130021

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jinhua Piao, MD.

Facility Name

Sichuan Provincial People's Hospital

City

Chengdu

ZIP/Postal Code

610072

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qian Peng, MD.

Facility Name

Chengdu Women's and Children's Central Hospital

City

Chengdu

ZIP/Postal Code

610074

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yiling Liu, MD.

Facility Name

Children's Hospital of Chongqing Medical University

City

Chongqing

ZIP/Postal Code

400014

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaoyan Liu, MD.

Facility Name

Hangzhou First people's Hospital

City

Hangzhou

ZIP/Postal Code

310006

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xianmei Huang, MD.

Facility Name

Inner Mongolia People's Hospital

City

Hohhot

ZIP/Postal Code

010017

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hua Zhu, MD.

Facility Name

Qilu Hospital of Shandong University

City

Jinan

ZIP/Postal Code

250012

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Cuifen Zhao, MD

Facility Name

Jiangxi Provincial Children's Hospital

City

Nanchang

ZIP/Postal Code

330006

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaohui Liu, MD.

Facility Name

Children's Hospital of Fudan University

City

Shanghai

ZIP/Postal Code

201102

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fang Liu, MD.

Facility Name

Shengjing Hospital of China Medical University

City

Shenyang

ZIP/Postal Code

110004

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ce Wang, MD.

Facility Name

Children's hospital of Soochow University

City

Suzhou

ZIP/Postal Code

215003

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Haitao Lv, MD.

Facility Name

Yuying Children's Hospital of Wenzhou Medical University

City

Wenzhou

ZIP/Postal Code

325027

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rongzhou Wu, MD

Facility Name

Union Hospital,Tongji Medical College of Huazhong University of Science and Technology

City

Wuhan

ZIP/Postal Code

430022

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qiupeng Wang, MD.

Facility Name

The Third Affiliated Hospital of ZhengzhouUniversity

City

Zhengzhou

ZIP/Postal Code

450052

Country

China

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yan Li, MD.

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34895290

Citation

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.

Results Reference

derived

Learn more about this trial

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

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