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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
Sponsored by
Children's Hospital of Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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
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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
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
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
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.
Arm Title
the standard+prednisolone group
Arm Type
Experimental
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 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.
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
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.
Time Frame
at one month of illness
Secondary Outcome Measure Information:
Title
Percentage of the need for additional treatment
Description
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.
Time Frame
from admission to discharge (about 2 weeks of illness)
Title
Duration of fever (hours) after initiation of initial IVIG infusion
Description
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.
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
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).).
Time Frame
from admission to 12 months of illness
Title
Changes in z scores of LAD throughout the study period
Description
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).).
Time Frame
from admission to 12 months of illness
Title
Changes in z scores of LCX throughout the study period
Description
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).).
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
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).).
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
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).).
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
No
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
Email
liufang@fudan.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Lan He, MD.
Phone
+8602164932026
Email
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
No
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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