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Kawasaki DiseasePhase 3NCT04535518

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

A Phase 3 study testing IVIG, Aspirin and Infliximab in people with Kawasaki Disease, run by Children's Hospital of Fudan University at 5 sites in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 1 month to 14 years
Conditions the study is for
Kawasaki Disease
What is being tested?
IVIG, Aspirin and Infliximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
5 sitesChina
Study dates
Oct 2020to Sep 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 14 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

China5 sites
  • Shanghai Children's Hospital

    Shanghai, 200062

  • Shanghai 10th People's Hospital

    Shanghai, 200072

  • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

    Shanghai, 200092

  • Shanghai Children's Medical Center

    Shanghai, 200127

  • Children's Hospital of Fudan University

    Shanghai, 201102

Other trials in China

About this study

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.

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).

Read the 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.

Being tested
IVIG, Aspirin, Infliximab
Keywords
Kawasaki disease, infliximab, coronary artery lesion
Medical subject headings
Mucocutaneous Lymph Node Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IVIGDrug

    Also called Intravenous Immunoglobulins, Human

    IVIG at a single dose of 2 g/kg

  • AspirinDrug

    Also called Acetylsalicylic acid

    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.

  • InfliximabDrug

    Also called Remicade

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

Study groups in NCT04535518
Study groupRoleWhat they receive
the standard groupActive comparator1. 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.
Receives: Drug: IVIG; Drug: Aspirin
the standard + infliximab groupExperimental1. 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.
Receives: Drug: IVIG; Drug: Aspirin; Drug: Infliximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: at one month of illness

Secondary outcomes (13)
  1. Percentage of the need for additional treatment

    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.

    Measured: from admission to discharge (about 2 weeks of illness)

  2. z scores of LMCA throughout the study period

    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.

    Measured: from admission to 12 months of illness

  3. z scores of LAD throughout the study period

    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.

    Measured: from admission to 12 months of illness

  4. z scores of LCX throughout the study period

    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.

    Measured: from admission to 12 months of illness

  5. z scores of the proximal segment of RCA throughout the study period

    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.

    Measured: from admission to 12 months of illness

  6. z scores of the middle segment of RCA throughout the study period

    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.

    Measured: from admission to 12 months of illness

  7. Duration of fever (hours) after initiation of initial IVIG infusion

    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.

    Measured: 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)

  8. Change in serum C-reactive protein (CRP) concentration

    CRP level is measured before initial IVIG infusion and 72 hours after completion of initial IVIG infusion.Change would be described by difference.

    Measured: from admission to 72 hours after completion of initial IVIG infusion

  9. Number of patients with serious adverse events

    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.

    Measured: from admission to 12 months of illness

  10. Percentage of the regression of coronary artery lesion (CAL) 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.

    Measured: at 3 months of illness

  11. Percentage of the regression of coronary artery lesion (CAL) 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.

    Measured: at 6 months of illness

  12. Percentage of the regression of coronary artery lesion (CAL) 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.

    Measured: at 9 months of illness

  13. Percentage of the regression of coronary artery lesion (CAL) 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.

    Measured: at 12 months of illness

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2020
  2. Study startOct 2020 (estimated)
  3. Primary completionSep 2022 (estimated)
  4. Study completionSep 2022 (estimated)

Why it stopped: lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04535518
Sponsor's protocol ID
KD-4-01
Status last verified
Mar 2021
First submitted
27 Aug 2020
Last updated
12 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 21074965

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IVIG, Aspirin and Infliximab in people with Kawasaki Disease, run by Children's Hospital of Fudan University at 5 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of the regression of coronary artery lesion (CAL) at one month of illness (time frame: at one month of illness). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04535518, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2021.

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