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

March 10, 2021 updated by: Children's Hospital of Fudan University

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.

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China, 200127
        • Shanghai Children's Medical Center
      • Shanghai, China, 201102
        • Children's Hospital of Fudan University
      • Shanghai, China, 200072
        • Shanghai 10th People's Hospital
      • Shanghai, China, 200062
        • Shanghai Children's Hospital
      • Shanghai, China, 200092
        • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 month to 14 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Drug: IVIG
IVIG at a single dose of 2 g/kg
Other Names:
  • Intravenous Immunoglobulins, Human
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.
Other Names:
  • Acetylsalicylic acid
Experimental: 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.
Drug: IVIG
IVIG at a single dose of 2 g/kg
Other Names:
  • Intravenous Immunoglobulins, Human
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.
Other Names:
  • Acetylsalicylic acid
Drug: Infliximab
Intravenous infliximab at single dose of 5 mg/kg, given more than 2 hours.
Other Names:
  • Remicade

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of the regression of coronary artery lesion (CAL) at one month of illness
Time Frame: 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of the need for additional treatment
Time Frame: from admission to discharge (about 2 weeks of illness)
Participants who have recurrent or persistent fever (axillary temperature ≥37.5°C or rectal temperature ≥38°C) after 36 hours of completion of initial IVIG infusion will be given additional treatment, including a second dose of IVIG (2 g/kg), or a high dose of methylprednisolone (10 to 30 mg/kg per day), or other immunosuppressive agents such as ciclosporin and cyclophosphamide, or a combination with two or more drugs, or even more aggressive treatment such as plasmapheresis, depending on patients'condition and physicians' experience. Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization.
from admission to discharge (about 2 weeks of illness)
z scores of LMCA throughout the study period
Time Frame: from admission to 12 months of illness
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of LMCA will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
from admission to 12 months of illness
z scores of LAD throughout the study period
Time Frame: from admission to 12 months of illness
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of LAD will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
from admission to 12 months of illness
z scores of LCX throughout the study period
Time Frame: from admission to 12 months of illness
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of LCX will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
from admission to 12 months of illness
z scores of the proximal segment of RCA throughout the study period
Time Frame: from admission to 12 months of illness
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of the proximal segment of RCA will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
from admission to 12 months of illness
z scores of the middle segment of RCA throughout the study period
Time Frame: from admission to 12 months of illness
This is a repeated measurement. Z score will be calculated based on the height, weight and coronary artery diameter (Journal of the American Society of Echocardiography, 2011, 24(1): 60-74.). The internal diameter of the middle segment of RCA will be measured by echocardiography at least seven time points: at enrollment, at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months of illness.
from admission to 12 months of illness
Duration of fever (hours) after initiation of initial IVIG infusion
Time Frame: 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)
Participants with an axillary temperature <37.5℃ (or rectal temperature <38℃) for more than 24 hours are considered afebrile. Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization. Record the time of the initiation of IVIG infusion and the time of the body temperature first becoming normal.
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)
Change in serum C-reactive protein (CRP) concentration
Time Frame: from admission to 72 hours after completion of initial IVIG infusion
CRP level is measured before initial IVIG infusion and 72 hours after completion of initial IVIG infusion.Change would be described by difference.
from admission to 72 hours after completion of initial IVIG infusion
Number of patients with serious adverse events
Time Frame: from admission to 12 months of illness
This is a composite outcome, including death, hypertension (defined as the blood pressure (BP) ≥90th percentile for age and height or ≥ 120/80 mmHg in the children younger than 13, and ≥ 120/80 mmHg in children ≥ 13 years), severe infection (such as septicopyemia, pulmonary infection and urinary system infection), allergic reactions, heart failure, thrombosis, etc.
from admission to 12 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 3 months of illness
Time Frame: at 3 months of illness
The regression of CAL is defined as the z < 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
at 3 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 6 months of illness
Time Frame: at 6 months of illness
The regression of CAL is defined as the z < 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
at 6 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 9 months of illness
Time Frame: at 9 months of illness
The regression of CAL is defined as the z < 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
at 9 months of illness
Percentage of the regression of coronary artery lesion (CAL) at 12 months of illness
Time Frame: at 12 months of illness
The regression of CAL is defined as the z < 2 of all coronary arteries of LMCA, LAD, LCX, and the proximal and middle segment of the RCA.
at 12 months of illness

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital of Fudan University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Shanghai 10th People's Hospital
Shanghai Children's Hospital
Shanghai Children's Medical Center
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Guoying Huang, MD., Children's Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 27, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 2, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 12, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KD-4-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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