Efficacy and Safety of Immunoglobulin Plus Firsekibart in Patients With Kawasaki Disease: An Exploratory Randomized Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Occurrence of coronary artery lesions (CAL) at one month of illness
研究概览
简要总结
This study evaluates the efficacy and safety of the addition of Firsekibart to standard initial treatment (intravenous immunoglobulin [IVIG] plus aspirin) in children with Acute Kawasaki Disease (KD) .
详细描述
This is a two-center, open-label, randomized controlled exploratory clinical trial in China. The investigators will enroll KD pediatric patients within 10 days of illness onset. Participants will be randomly assigned in a 1:2 ratio to the experimental group (receiving 3 mg/kg Firsekibart plus 2 g/kg IVIG and 30 mg/kg aspirin) or the control group (receiving 2 g/kg IVIG and 30 mg/kg aspirin). Baseline characteristics of each participant will be collected, including sex, age at 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, and 6 months after illness onset to assess the coronary artery lesions. This study aims to determine the therapeutic potential of standard therapy combined with Firsekibart in the acute phase of KD for reducing the incidence of coronary artery lesions (CAL) , decreasing IVIG resistance, and improving inflammation control.
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. Outcome assessors (i.e., echocardiographers) and statisticians will be unaware of the assignments throughout the trial until completion of the statistical analysis.
入排标准
- 年龄范围
- 29 Days 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meeting diagnostic criteria for Kawasaki disease (KD) released by American Heart Association (AHA) in 2024
- •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 >28 days，<18 years
排除标准
- •Receiving steroids or other immunosuppressive agents in the previous 30 days;
- •With a previous history of KD;
- •Afebrile before enrolment;
- •Contraindications for subcutaneous injection, including severe local skin infection, ulceration, etc;
- •Known hypersensitivity to immunoglobulins, Firsekibart, or any of the excipients;
- •With suspected infectious diseases including sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella and influenza, etc;
- •With serious immune diseases, such as immunodeficiency, or chromosomal abnormalities;
- •With severe hepatic dysfunction (ALT > 3 times the upper limit of normal) prior to treatment
- •Unwillingness to provide written informed consent;
- •Unlikely to complete at least 3 months of follow-up;
- •Any other conditions deemed unsuitable for enrolment by investigators.
研究组 & 干预措施
Firsekibart + standard treatment group
- Firsekibart 3 mg/kg by a single subcutaneous injection prior to IVIG infusion. After a 30-minute observation period confirming the absence of adverse reactions, the IVIG infusion is initiated.
- IVIG 2g/kg once, given over 8 to 12 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.
【Standard treatment also follow the 2024 AHA Guidelines of Kawasaki Disease】
Discomfort occurring during the observation period after Firsekibart will be treated symptomatically, and standard treatment will subsequently be provided as needed based on the participant's condition and the physician's experience.
In the event of a Grade ≥3 allergic reaction, epinephrine will be administered as needed.
Management of IVIG resistance, aspirin intolerance will be the same as in the control group.
干预措施: Firsekibart (Drug)
standard treatment group
【Standard treatment follow the 2024 AHA Guidelines of Kawasaki Disease】
- IVIG 2g/kg once, given over 8 to 12 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 illness onset.
Participants with persistent or recurrent fever (temperature of ≥38°C ) 36 hours after completion of the first IVIG infusion are defined as having resistance to IVIG and will receive rescue therapy. The rescue therapy will be chosen on the basis of participant's condition and the physician's experience.
Participants intolerant to aspirin may receive oral clopidogrel as an alternative.
干预措施: Aspirin (Drug)
standard treatment group
【Standard treatment follow the 2024 AHA Guidelines of Kawasaki Disease】
- IVIG 2g/kg once, given over 8 to 12 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 illness onset.
Participants with persistent or recurrent fever (temperature of ≥38°C ) 36 hours after completion of the first IVIG infusion are defined as having resistance to IVIG and will receive rescue therapy. The rescue therapy will be chosen on the basis of participant's condition and the physician's experience.
Participants intolerant to aspirin may receive oral clopidogrel as an alternative.
干预措施: IVIG (Drug)
Firsekibart + standard treatment group
- Firsekibart 3 mg/kg by a single subcutaneous injection prior to IVIG infusion. After a 30-minute observation period confirming the absence of adverse reactions, the IVIG infusion is initiated.
- IVIG 2g/kg once, given over 8 to 12 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.
【Standard treatment also follow the 2024 AHA Guidelines of Kawasaki Disease】
Discomfort occurring during the observation period after Firsekibart will be treated symptomatically, and standard treatment will subsequently be provided as needed based on the participant's condition and the physician's experience.
In the event of a Grade ≥3 allergic reaction, epinephrine will be administered as needed.
Management of IVIG resistance, aspirin intolerance will be the same as in the control group.
干预措施: IVIG (Drug)
Firsekibart + standard treatment group
- Firsekibart 3 mg/kg by a single subcutaneous injection prior to IVIG infusion. After a 30-minute observation period confirming the absence of adverse reactions, the IVIG infusion is initiated.
- IVIG 2g/kg once, given over 8 to 12 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.
【Standard treatment also follow the 2024 AHA Guidelines of Kawasaki Disease】
Discomfort occurring during the observation period after Firsekibart will be treated symptomatically, and standard treatment will subsequently be provided as needed based on the participant's condition and the physician's experience.
In the event of a Grade ≥3 allergic reaction, epinephrine will be administered as needed.
Management of IVIG resistance, aspirin intolerance will be the same as in the control group.
干预措施: Aspirin (Drug)
结局指标
主要结局
Occurrence of coronary artery lesions (CAL) at one month of illness
时间窗: from admission to 1 month of illness onset
Two-dimensional echocardiography will be performed to evaluate CAL at 1 month of illness. Measurements for each patient include 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≥2.5 of any coronary artery of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
Occurrence of the need for rescue therapy
时间窗: from admission to discharge (about 2 weeks of illness onset)
Temperature will be measured every 6 hours a day during hospitalization. Participants who have recurrent or persistent fever (temperature ≥38°C) after 36 hours of completion of initial IVIG infusion will be given rescue therapy.
次要结局
- Duration of fever (hours) after initiation of initial IVIG infusion(from initiation of the initial IVIG infusion to the first recorded afebrile status (up to 60 hours after the infusion of IVIG))
- Change in serum interleukin (IL)-1β concentration(from admission to 1 month of illness onset)
- Occurrence of coronary artery lesions (CAL) at 2 weeks of illness(from admission to 2 weeks of illness onset)
- Changes in z scores of LCX(from admission to 6 months of illness onset)
- Occurrence of coronary artery lesions (CAL) at 3 months of illness(from admission to 3 months of illness onset)
- Occurrence of medium-to-giant coronary artery aneurysms (CAAs)(from admission to 6 months of illness onset)
- Changes in z scores of LAD(from admission to 6 months of illness onset)
- Changes in z scores of LMCA(from admission to 6 months of illness onset)
- Changes in z scores of the proximal segment of RCA(from admission to 6 months of illness onset)
- Changes in z scores of the middle segment of RCA(from admission to 6 months of illness onset)
- Occurrence of CAL regression(from admission to 6 months of illness onset)
- Occurrence of CAL progression(from admission to 6 months of illness onset)
- Occurrence of adverse events(from admission to 6 months of illness onset)
- Change in serum C-reactive protein (CRP) concentration(from admission to 1 month of illness onset)
- Change in Serum Amyloid A (SAA) concentration(from admission to 1 month of illness onset)
- Change in serum interleukin (IL)-1β concentration(from admission to 72 hours after completion of the initial IVIG infusion)