Efficacy of Primary Treatment With Immunoglobulin Plus Infliximab for the Early Regression of Coronary Artery Lesion in Kawasaki Disease: a Multicenter, Open-label, Blinded-end Randomized Controlled Study.
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 5
- 主要终点
- Percentage of the regression of coronary artery lesion (CAL) at one month of illness
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 1 Month 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meeting diagnostic criteria for KD released by American Heart Association (AHA) in 2017, including complete KD (also sometimes referred to as typical or classic KD) and incomplete KD ((also sometimes referred to as atypical KD);
- •Diagnosed within 14 days of illness (including the 14th day, considering the first day of illness as the first day of fever);
- •Not treated with IVIG or other treatments for KD yet;
- •Z score of any coronary artery of LMCA, LAD, LCX, the proximal and middle segment of RCA ≥ 2 calculated based on the height, weight and coronary artery diameter measured by echocardiography;
- •Aged between one month and 14 years.
排除标准
- •Receiving steroids or other immunosuppressive agents in the previous 30 days;
- •With a previous history of KD;
- •Afebrile and all the inflammation indicators (including white blood cell count, CRP, and erythrocyte sedimentation) become normal before enrolment;
- •With suspected infectious diseases including tuberculosis, sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella, influenza, EBV infection, etc;
- •With serious immune diseases such as immunodeficiency or chromosomal abnormalities;
- •Unable to be followed up for at least 1 year.
研究组 & 干预措施
the standard group
- IVIG 2 g/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 72 hours and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.
干预措施: IVIG (Drug)
the standard group
- IVIG 2 g/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 72 hours and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.
干预措施: Aspirin (Drug)
the standard + infliximab group
- IVIG 2 g/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 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.
干预措施: IVIG (Drug)
the standard + infliximab group
- IVIG 2 g/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 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.
干预措施: Aspirin (Drug)
the standard + infliximab group
- IVIG 2 g/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 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.
干预措施: Infliximab (Drug)
结局指标
主要结局
Percentage of the regression of coronary artery lesion (CAL) at one month of illness
时间窗: 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).
次要结局
- 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))
- Percentage of the need for additional treatment(from admission to discharge (about 2 weeks of illness))
- z scores of LMCA throughout the study period(from admission to 12 months of illness)
- z scores of LAD throughout the study period(from admission to 12 months of illness)
- z scores of LCX throughout the study period(from admission to 12 months of illness)
- z scores of the proximal segment of RCA throughout the study period(from admission to 12 months of illness)
- Change in serum C-reactive protein (CRP) concentration(from admission to 72 hours after completion of initial IVIG infusion)
- z scores of the middle segment of RCA throughout the study period(from admission to 12 months of illness)
- Number of patients with serious adverse events(from admission to 12 months of illness)
- Percentage of the regression of coronary artery lesion (CAL) at 3 months of illness(at 3 months of illness)
- Percentage of the regression of coronary artery lesion (CAL) at 6 months of illness(at 6 months of illness)
- Percentage of the regression of coronary artery lesion (CAL) at 9 months of illness(at 9 months of illness)
- Percentage of the regression of coronary artery lesion (CAL) at 12 months of illness(at 12 months of illness)