Results Summary

What was the research about?

Kawasaki disease is a rare childhood illness that inflames blood vessels. Symptoms include high fever; rash; and swollen tongue, hands, and feet. The disease can sometimes cause a dangerous bulge, called an aneurysm, in the blood vessels that supply the heart.

Most children recover from Kawasaki disease after treatment with intravenous immunoglobulin, or IVIG. But in 10 to 20 percent of children, fever persists or returns, which doctors call resistant Kawasaki disease. These children have a high risk of aneurysm.

In this study, the research team looked at the safety and effectiveness of two treatments for children with resistant Kawasaki disease:

  • A second dose of IVIG
  • A medicine called infliximab

What were the results?

Infliximab was safe and effective for children with resistant Kawasaki disease. Compared with children who received a second dose of IVIG, children who received infliximab:

  • Were less likely to have fever after treatment.
  • Had shorter hospital stays.
  • Had fewer side effects and serious adverse events such as anemia. The research team defined a serious adverse event as one that resulted in a hospital stay, disability, or even death.

The two treatments didn’t differ in:

  • Heart scores that measure if a child has an aneurysm.
  • Lab tests that measure inflammation.

Who was in the study?

The study included 103 children ages 4 weeks to 17 years with resistant Kawasaki disease. All received care at one of 30 health centers across the United States. Among children, 58 percent were White, 18 percent were Black or African American, 11 percent were Asian, 8 percent were more than one race, and less than 4 percent were unknown or other races. The average age was 2, and 57 percent were boys.

What did the research team do?

The research team assigned children by chance to receive either a second dose of IVIG or infliximab. All children had received a first dose of IVIG and had a fever that persisted or returned within 36 hours. Children who still had a fever seven days later took the other treatment.

Parents completed surveys about their child’s symptoms four times on the first day of treatment and then once daily for two weeks. Children had an echocardiogram when they started the study and two weeks after leaving the hospital. An echocardiogram uses sound waves to take pictures of the heart.

People who had Kawasaki disease as children, and parents of children with Kawasaki disease, gave input on the study.

What were the limits of the study?

Doctors across health centers may have interpreted echocardiogram results differently. Also, the study didn’t enroll children who already had aneurysms from Kawasaki disease. Results may differ for these patients.

Future research could look at the best dose of infliximab for children with resistant Kawasaki disease. Studies could also include children with heart damage from Kawasaki disease.

How can people use the results?

Doctors and parents can use these results when considering treatment for children with resistant Kawasaki disease.

Final Research Report

View this project's final research report.

Journal Citations

Article Highlight: The KIDCARE Study compared treatment strategies for resistant Kawasaki disease. The research team assessed the effectiveness of a medicine called infliximab compared to giving a second dose of IVIG. More than 100 children who had resistant disease and received care at 30 health centers across the United States were evaluated. The team found that children who received infliximab had shorter hospital stays and experienced fewer side effects, including anemia, than those given a second dose of IVIG. This is one of few trials to evaluate therapies for a rare group of patients experiencing the already rare condition of Kawasaki disease. These study findings were published in The Lancet Child & Adolescent Health.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.  

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

  • The reviewers asked the researchers to confirm their statements regarding the amount of missing data in the study, in particular whether each participant had seven days of follow-up outcomes for analyses. The researchers included that information in their participant flow diagram, noting that three patients did not have those outcomes available for seven days. The reviewers also commented on the substantial missing data in the secondary outcomes of symptom reporting, which the researchers acknowledged in their limitations section.
  • The reviewers questioned the generalizability of the study results given the apparent exclusion of more severely affected children who would be taking steroids. The researchers noted that in some clinic sites included in this study, the standard of care for children who have had one round intravenous immunoglobulin (IVIG) and aspirin treatment and who then become febrile is immediate treatment with IVIG again. Only children in clinics that did not apply this automatic second round of IVIG were included in the study and randomized to IVIG or infliximab. The researchers acknowledged that the study recruitment might have therefore been biased toward lower-risk patients, reducing the generalizability of the results. 
  • Reviewers noted that fever after IVIG treatment could be a side effect of the treatment or an indication of disease activity, and asked whether the researchers were able to identify the cause of the fever. The researchers explained that fever caused by IVIG treatment usually manifests within a few hours after administration, but the outcome of fever reduction was measured 24 hours after administration. If fever persisted at that point, patients would be switched to the other treatment condition.

Conflict of Interest Disclosures

Project Information

Jane C. Burns, MD
Katherine K. Kim, PhD, MPH, MBA
University of California San Diego
$3,109,875
10.25302/04.2023.CER.160234473
A Stakeholder-Driven Comparative Effectiveness Study of Treatments to Prevent Coronary Artery Damage in Patients with Resistant Kawasaki Disease

Key Dates

December 2016
May 2023
2016
2022

Study Registration Information

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Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
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Last updated: February 15, 2024