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

NCT04535518 | Withdrawn Phase 3 DMC

• 1 other identifier: KD-4-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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).

Conditions

Kawasaki Disease

Keywords

Kawasaki disease; infliximab; coronary artery lesion

Outcome Measures

Primary Outcomes (1)

• 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).

  at one month of illness

Secondary Outcomes (13)

• 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

Study Arms (2)

the standard group

ACTIVE COMPARATOR

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.

Drug: IVIG; Drug: Aspirin

the standard + infliximab group

EXPERIMENTAL

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.

Drug: IVIG; Drug: Aspirin; Drug: Infliximab

Interventions

IVIG DRUG

IVIG at a single dose of 2 g/kg

Also known as: Intravenous Immunoglobulins, Human

the standard + infliximab group; the standard group

Aspirin 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.

Also known as: Acetylsalicylic acid

the standard + infliximab group; the standard group

Infliximab DRUG

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

Also known as: Remicade

the standard + infliximab group

Eligibility Criteria

• Age: 1 Month - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Shanghai Children's Hospital: collaborator
• Shanghai Children's Medical Center: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai 10th People's Hospital: collaborator

Study Sites (5)

Shanghai Children's Hospital

Shanghai, 200062, China

Location

Shanghai 10th People's Hospital

Shanghai, 200072, China

Location

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, 200092, China

Location

Shanghai Children's Medical Center

Shanghai, 200127, China

Location

Children's Hospital of Fudan University

Shanghai, 201102, China

Location

Related Publications (1)

• 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.

  PMID: 21074965 BACKGROUND

MeSH Terms

Conditions

Mucocutaneous Lymph Node Syndrome

Interventions

Immunoglobulins, Intravenous; Aspirin; Infliximab

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Antibodies, Monoclonal

Study Officials

• Guoying Huang, MD.

  Children's Hospital of Fudan University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 2, 2020
• Study Start: October 1, 2020
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: March 12, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)