Efficacy of Immunoglobulin Plus Infliximab for the Early Regression of Coronary Artery Lesion in Kawasaki Disease

NCT ID: NCT04535518

Last Updated: 2021-03-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-31
• Study Completion Date: 2022-09-30

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.

Conditions

Kawasaki Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

the standard group

1. IVIG 2 g/kg once, given within 12 to 24 hours;

2. 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.

Group Type: ACTIVE_COMPARATOR

IVIG

Intervention Type: DRUG

IVIG at a single dose of 2 g/kg

Aspirin

Intervention Type: DRUG

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.

the standard + infliximab group

1. IVIG 2 g/kg once, given within 12 to 24 hours;

2. 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.

3. Intravenous infliximab at single dose of 5 mg/kg, given more than 2 hours.

Group Type: EXPERIMENTAL

IVIG

Intervention Type: DRUG

IVIG at a single dose of 2 g/kg

Aspirin

Intervention Type: DRUG

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.

Infliximab

Intervention Type: DRUG

Intravenous infliximab at single dose of 5 mg/kg, given more than 2 hours.

Interventions

IVIG

IVIG at a single dose of 2 g/kg

Intervention Type: 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 72 hours and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.

Intervention Type: DRUG

Infliximab

Intravenous infliximab at single dose of 5 mg/kg, given more than 2 hours.

Intervention Type: DRUG

Other Intervention Names

Intravenous Immunoglobulins, Human; Acetylsalicylic acid; Remicade

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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Children's Hospital

OTHER

Sponsor Role: collaborator

Shanghai Children's Medical Center

OTHER

Sponsor Role: collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Shanghai 10th People's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guoying Huang, MD.

Role: STUDY_DIRECTOR

Children's Hospital of Fudan University

Locations

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

Children's Hospital of Fudan University

Shanghai, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 21074965 (View on PubMed)

Other Identifiers

KD-4-01

Identifier Type: -

Identifier Source: org_study_id