This study evaluates the efficacy of the addition of infliximab to conventional initial treatment (intravenous immunoglobulin \[IVIG\] plus aspirin) in early regression of coronary artery lesion in patients with Kawasaki disease (KD).
This is a multicenter, open-label, blind-end, randomized controlled trial at 5 hospitals in Shanghai, China. The KD children diagnosed within 14 days of onset according to the diagnostic criteria for KD released by American Heart Association (AHA) in 2017 will be considered for participants in the trial. The patients meeting eligibility criteria will be randomly assigned in a 1:1 ratio to the control group (receiving 2 g/kg\*1 IVIG and 30 mg/kg/d aspirin) or intervention group (receiving 2 g/kg\*1 IVIG, 30 mg/kg/d aspirin and additional 5 mg/kg\*1 infliximab) based on the randomly block design (block sizes 4). Baseline characteristics of each participant will be collected, including sex, age of onset, height, body weight, subtype of KD, fever days before initial IVIG, other clinical manifestations, echocardiographic findings at enrolment, and a series of pre-IVIG laboratory tests. Two-dimensional echocardiography will be performed at least 7 timepoints: at admission, 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months after onset of KD to assess the coronary artery lesions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
IVIG at a single dose of 2 g/kg
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 72 hours and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.
Intravenous infliximab at single dose of 5 mg/kg, given more than 2 hours.
Shanghai Children's Hospital
Shanghai, China
Shanghai 10th People's Hospital
Shanghai, China
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai Children's Medical Center
Shanghai, China
Percentage of the regression of coronary artery lesion (CAL) at one month of illness
The regression of CAL is defined as z \< 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.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):60-74).
Time frame: at one month of illness
Percentage of the need for additional treatment
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, including a second dose of IVIG (2 g/kg), or a high dose of methylprednisolone (10 to 30 mg/kg per day), or other immunosuppressive agents such as ciclosporin and cyclophosphamide, or a combination with two or more drugs, or even more aggressive treatment such as plasmapheresis, depending on patients'condition and physicians' experience. Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization.
Time frame: from admission to discharge (about 2 weeks of illness)
z scores of LMCA throughout the study period
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of LMCA will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
Time frame: from admission to 12 months of illness
z scores of LAD throughout the study period
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Children's Hospital of Fudan University
Shanghai, China
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of LAD will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
Time frame: from admission to 12 months of illness
z scores of LCX throughout the study period
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of LCX will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
Time frame: from admission to 12 months of illness
z scores of the proximal segment of RCA throughout the study period
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of the proximal segment of RCA will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
Time frame: from admission to 12 months of illness
z scores of the middle segment of RCA throughout the study period
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of the middle segment of RCA will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
Time frame: from admission to 12 months of illness
Duration of fever (hours) after initiation of initial IVIG infusion
Participants with an axillary temperature \<37.5℃ (or rectal temperature \<38℃) for more than 24 hours are considered afebrile. Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization. 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)
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.Change would be described by difference.
Time frame: 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 (defined as the blood pressure (BP) ≥90th percentile for age and height or ≥ 120/80 mmHg in the children younger than 13, and ≥ 120/80 mmHg in children ≥ 13 years), severe infection (such as septicopyemia, pulmonary infection and urinary system infection), allergic reactions, heart failure, thrombosis, etc.
Time frame: from admission to 12 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 3 months of illness
The regression of CAL is defined as the z \< 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
Time frame: at 3 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 6 months of illness
The regression of CAL is defined as the z \< 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
Time frame: at 6 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 9 months of illness
The regression of CAL is defined as the z \< 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
Time frame: at 9 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 12 months of illness
The regression of CAL is defined as the z \< 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
Time frame: at 12 months of illness