Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05287412

Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children

Multi-system Inflammatory Syndrome in Children (MIS-C) is a new condition related to COVID-19, the study investigators are still learning about its causes, effects, and long-term impact. "Long-Term Outcomes after the Multisystem Inflammatory Syndrome In Children", the Coronavirus MUSIC Study, is a research study funded by NIH and the National Heart, Lung, and Blood Institute. The study investigators hope to enroll at least 900 young people with MIS-C at children's medical centers in the U.S. and Canada. This research study will help us learn more about MIS-C and its effects on the long-term health of children.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Multisystem Inflammatory Syndrome in Children (MIS-C) pediatric multisystem inflammatory disease, COVID-19 related

Age range

Up to 21 year

Sex eligibility

All sexes

Study type

Observational

Primary location

The Hospital for Sick Children, Toronto, Ontario, Canada

Loading trial locations.

About this study

This study is an observational cohort study that will use routinely collected clinical and cardiac (EKG, echocardiogram, Cardiac MRI, exercise testing) data to assess the association between MIS-C and cardiac outcomes within the first year after hospital discharge. Research funding will be available for EKGs, echocardiograms and MRIs in protocol windows that are not ordered by primary caregivers. The principal goal is to determine the spectrum and early time course of coronary artery involvement, LV systolic function, and arrhythmias or conduction system abnormalities, and, using these data, to define associated clinical and laboratory factors. The study investigators planned to include all eligible patients, including retrospective cases beginning January 1, 2020, with follow-up (in-person or telehealth) to up within one year and annual medical history forms until up to 5 years have elapsed since illness onset. Because many patients will have been identified by retrospective review, the study team will obtain consent at different times in their illness course. For this reason, it may be hard to reach some patients and their families. Waiver of consent will be obtained after three attempts have been made to locate the patient and family without success, as well as for the rare child who dies before informed consent can be obtained. The study investigators will include a HIPAA-compliant cryptographic algorithm to create a sharable "hashed" identifier from patient information. If blood work for research purposes is added on to usual clinically indicated blood work during follow-up visits, this will be covered by other informed consent forms.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age <21 years.
  • Fever ≥38°C for ≥24 hours, or report of subjective fever lasting ≥24 hours.
  • Laboratory evidence of inflammation, including, but not limited to, one or more of the following: an elevated CRP, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, LDH, or IL-6, elevated neutrophils, reduced lymphocytes and low albumin.
  • Evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement, based on clinical judgment from record review, discharge diagnosis, laboratory or diagnostic tests. Organ system involvement includes but is not limited to cardiac, renal, respiratory, hematologic including coagulopathy, gastrointestinal including liver, dermatologic or neurological.
  • Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms

Exclusion criteria

  • No plausible alternative diagnosis, such as bacterial sepsis, murine typhus, staphylococcal or streptococcal shock syndromes

Treatment and study plan

Primary outcomes

  1. worst-ever LV ejection fraction

    Time frame: hospital admission through 5 years post-hospitalization

    worst left ventricular (LV) ejection fraction from core lab echo read during MUSIC study

  2. worst-ever maximum z score of the proximal LAD or RCA

    Time frame: hospital admission through 5 years post-hospitalization

    worst maximum z-score of the proximal left anterior descending coronary artery (LAD) or right coronary artery (RCA) from core lab echo read; z-scores to be calculated via Boston z-score calculator (primary) and Pediatric Heart Network z-score calculator (secondary); higher z-scores are worse

Secondary outcomes

  1. Occurrence of a proximal LAD or RCA z score of ≥2.5 on any echocardiogram

    Time frame: hospital admission through 5 years post-hospitalization

    proximal left anterior descending coronary artery (LAD) or right coronary artery (RCA) ≥2.5 from any core lab echo read

  2. Occurrence of aneurysms by Japanese Ministry of Health criteria

    Time frame: hospital admission through 5 years post-hospitalization

    Occurrence of aneurysms by Japanese Ministry of Health criteria applied to core lab echo reads

  3. Individual z scores for LMCA, RCA and LAD

    Time frame: hospital admission through 5 years post-hospitalization

    Individual z scores for left main coronary artery (LMCA), right coronary artery (RCA) and proximal left anterior descending coronary artery (LAD) as per core lab echo reads; higher z-scores are worse

  4. LVEDV z score

    Time frame: hospital admission through 5 years post-hospitalization

    left ventricular (LV) size as measured by left ventricular end-diastolic volume (LVEDV) z score

  5. LVEF

    Time frame: hospital admission through 5 years post-hospitalization

    left ventricular (LV) function as measured by left ventricular ejection fraction (LVEF)

  6. LVSF

    Time frame: hospital admission through 5 years post-hospitalization

    left ventricular (LV) function as measured by left ventricular shortening fraction (LVSF)

  7. The percentage of patients who had LV ejection of <55%, and further categorization of 45-54% (i.e., mildly depressed systolic function), 35-44% (moderately depressed systolic function) and <35% (severely depressed systolic function) on any echocardiogram

    Time frame: hospital admission through 5 years post-hospitalization

    The percentage of patients who had left ventricular (LV) ejection of <55%, and further categorization of 45-54% (i.e., mildly depressed systolic function), 35-44% (moderately depressed systolic function) and <35% (severely depressed systolic function) on any echocardiogram read by the core lab

  8. LV strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view)

    Time frame: hospital admission through 5 years post-hospitalization

    left ventricular (LV) strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view) on core lab echo read

  9. Qualitative assessment of RV systolic function

    Time frame: hospital admission through 5 years post-hospitalization

    Qualitative assessment of right ventricular (RV) systolic function on core lab echo read

  10. Qualitative assessment of RV global longitudinal strain

    Time frame: hospital admission through 5 years post-hospitalization

    Qualitative assessment, if possible, of right ventricular (RV) global longitudinal strain on core lab echo read

  11. Presence and degree of mitral and aortic regurgitation

    Time frame: hospital admission through 5 years post-hospitalization

    Presence and degree of mitral and aortic regurgitation on echo core lab read

  12. LV diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow

    Time frame: hospital admission through 5 years post-hospitalization

    left ventricular (LV) diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow on echo core lab read

  13. Presence and size of pericardial effusion

    Time frame: hospital admission through 5 years post-hospitalization

    Presence and size of pericardial effusion on echo core lab read

  14. The occurrence of arrhythmias and conduction system disturbances by in-hospital monitoring, electrocardiograms, and exercise testing at 3 months in those with a history of ≥moderate systolic dysfunction when age and maturity permit

    Time frame: 3 months post-discharge

    The occurrence of arrhythmias and conduction system disturbances by in-hospital monitoring, electrocardiograms, and exercise testing at 3 months in those with a history of ≥moderate systolic dysfunction when age and maturity permit

  15. MRI LVEF

    Time frame: hospital admission through 5 years post-hospitalization

    LVEF on MRI core lab read

  16. MRI RVEF

    Time frame: hospital admission through 5 years post-hospitalization

    RVEF on MRI core lab read

  17. valvar regurgitation

    Time frame: hospital admission through 5 years post-hospitalization

    valvar regurgitation on MRI core lab read

  18. myocardial late gadolinium enhancement (LGE)

    Time frame: hospital admission through 5 years post-hospitalization

    percent with and distribution of myocardial late gadolinium enhancement (LGE) on MRI core lab read

  19. abnormal T2-weighted imaging

    Time frame: hospital admission through 5 years post-hospitalization

    percent abnormal T2-weighted imaging on MRI core lab read

  20. elevated T2

    Time frame: hospital admission through 5 years post-hospitalization

    percent with elevated T2 on MRI core lab read

  21. elevated native T1

    Time frame: hospital admission through 5 years post-hospitalization

    percent with elevated native T1 on MRI core lab read

  22. elevated extracellular volume fraction

    Time frame: hospital admission through 5 years post-hospitalization

    percent with elevated extracellular volume fraction on MRI core lab read

  23. coronary artery dilation

    Time frame: hospital admission through 5 years post-hospitalization

    percent with coronary artery dilation on MRI core lab read

  24. CMR abnormal, equivocal, or negative

    Time frame: hospital admission through 5 years post-hospitalization

    final interpretation of CMR as abnormal, equivocal, or negative (i.e., no abnormal or equivocal findings) on MRI core lab read

  25. Other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic

    Time frame: hospital admission through 5 years post-hospitalization

    percent with other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic

  26. CRP

    Time frame: hospital admission through 5 years post-hospitalization

    C-Reactive Protein (CRP) as a laboratory marker of inflammation

  27. Admission to ICU

    Time frame: hospital admission through 5 years post-hospitalization

    percent with admission to ICU

  28. Maximal vasoactive inotrope score

    Time frame: from MIS-C hospital admission to MIS-C hospital discharge

    Maximal vasoactive inotrope score

  29. Hospital length of stay

    Time frame: from MIS-C hospital admission to MIS-C hospital discharge

    Hospital length of stay

  30. Symptom duration

    Time frame: hospital admission through 5 years post-hospitalization

    Symptom duration

  31. Major medical events

    Time frame: hospital admission through 5 years post-hospitalization

    percent with major medical events (e.g., stroke, need for extracorporeal therapies such as renal replacement therapy, plasma exchange, ECMO, VAD)

  32. Mortality

    Time frame: hospital admission through 5 years post-hospitalization

    Percent mortality

  33. Global Health - FSS

    Time frame: hospital admission through 5 years post-hospitalization

    Global Health as measured by Functional Status Score [FSS]: range 6-30, lower is better

  34. Global Health - PROMIS

    Time frame: hospital admission through 5 years post-hospitalization

    Global Health as measured by Parent-Reported Outcomes Measurement Information Systems [PROMIS] Instrument: range 7-35, higher is better

Sponsors and collaborators

Lead sponsor

Carelon Research

Other

Registry information

Acronym: MUSIC

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Mar 18, 2022
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.