Clinical trial NCT04535518: Efficacy of Immunoglobulin Plus Infliximab for the Early Regression of Coronary Artery Lesion in Kawasaki Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Kawasaki Disease
Keywords: Kawasaki disease
infliximab
coronary artery lesion
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: Shanghai Children's Hospital
name: Shanghai Children's Medical Center
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai 10th People's Hospital
First posted: 2020-09-02
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of the regression of coronary artery lesion (CAL) at one month of illness
timeFrame: at one month of illness
Secondary outcomes:
measure: Percentage of the need for additional treatment
timeFrame: from admission to discharge (about 2 weeks of illness)
measure: z scores of LMCA throughout the study period
timeFrame: from admission to 12 months of illness
measure: z scores of LAD throughout the study period
timeFrame: from admission to 12 months of illness
measure: z scores of LCX throughout the study period
timeFrame: from admission to 12 months of illness
measure: z scores of the proximal segment of RCA throughout the study period
timeFrame: from admission to 12 months of illness
measure: z scores of the middle segment of RCA throughout the study period
timeFrame: from admission to 12 months of illness
measure: Duration of fever (hours) after initiation of initial IVIG infusion
timeFrame: 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)
measure: Change in serum C-reactive protein (CRP) concentration
timeFrame: from admission to 72 hours after completion of initial IVIG infusion
measure: Number of patients with serious adverse events
timeFrame: from admission to 12 months of illness
measure: Percentage of the regression of coronary artery lesion (CAL) at 3 months of illness
timeFrame: at 3 months of illness
measure: Percentage of the regression of coronary artery lesion (CAL) at 6 months of illness
timeFrame: at 6 months of illness
measure: Percentage of the regression of coronary artery lesion (CAL) at 9 months of illness
timeFrame: at 9 months of illness
measure: Percentage of the regression of coronary artery lesion (CAL) at 12 months of illness
timeFrame: at 12 months of illness
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Hospital
city: Shanghai
country: China
facility: Shanghai 10th People's Hospital
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
Study officials:
affiliation: Children's Hospital of Fudan University
name: Guoying Huang, MD.
role: STUDY_DIRECTOR
References:
citation: Dallaire F, Dahdah N. New equations and a critical appraisal of coronary artery Z scores in healthy children. J Am Soc Echocardiogr. 2011 Jan;24(1):60-74. doi: 10.1016/j.echo.2010.10.004. Epub 2010 Nov 13.