Efficacy of Immunoglobulin Plus Prednisolone in Reducing Coronary Artery Lesion in Patients With Kawasaki Disease
Study Details
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) .
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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 Design
Arms and Interventions
| 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:
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:
|
| 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, 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:
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:
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, 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:
|
Outcome Measures
Primary Outcome Measures
- Percentage of coronary artery lesions(CAL) at one month of illness [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 [from admission to discharge (about 2 weeks of illness)]
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 [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)]
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 [from admission to 12 months of illness]
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 [from admission to 12 months of illness]
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 [from admission to 12 months of illness]
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 [from admission to 12 months of illness]
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 [from admission to 12 months of illness]
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 [from admission to 72 hours after completion of initial IVIG infusion]
CRP level is measured before initial IVIG infusion and 72 hours after completion of initial IVIG infusion.
- Number of patients with serious adverse events [from admission to 3 months of illness]
This is a composite outcome, including death, hypertension, severe infection, allergic reactions, heart failure, thrombosis, etc.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Children's Hospital | Beijing | China | 100045 | |
| 2 | The First Hospital of Jilin University | Chang chun | China | 130021 | |
| 3 | Sichuan Provincial People's Hospital | Chengdu | China | 610072 | |
| 4 | Chengdu Women's and Children's Central Hospital | Chengdu | China | 610074 | |
| 5 | Children's Hospital of Chongqing Medical University | Chongqing | China | 400014 | |
| 6 | Hangzhou First people's Hospital | Hangzhou | China | 310006 | |
| 7 | Inner Mongolia People's Hospital | Hohhot | China | 010017 | |
| 8 | Qilu Hospital of Shandong University | Jinan | China | 250012 | |
| 9 | Jiangxi Provincial Children's Hospital | Nanchang | China | 330006 | |
| 10 | Children's Hospital of Fudan University | Shanghai | China | 201102 | |
| 11 | Shengjing Hospital of China Medical University | Shenyang | China | 110004 | |
| 12 | Children's hospital of Soochow University | Suzhou | China | 215003 | |
| 13 | Yuying Children's Hospital of Wenzhou Medical University | Wenzhou | China | 325027 | |
| 14 | Union Hospital,Tongji Medical College of Huazhong University of Science and Technology | Wuhan | China | 430022 | |
| 15 | The Third Affiliated Hospital of ZhengzhouUniversity | Zhengzhou | China | 450052 |
Sponsors and Collaborators
- Children's Hospital of Fudan University
- 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
Investigators
- Study Director: Fang Liu, MD., Children's Hospital of Fudan University
Study Documents (Full-Text)
More Information
Publications
None provided.- KD-3-01