Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children
- Conditions
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Registration Number
- NCT05287412
- Lead Sponsor
- Carelon Research
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1200
- 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
- No plausible alternative diagnosis, such as bacterial sepsis, murine typhus, staphylococcal or streptococcal shock syndromes
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method worst-ever LV ejection fraction hospital admission through 5 years post-hospitalization worst left ventricular (LV) ejection fraction from core lab echo read during MUSIC study
worst-ever maximum z score of the proximal LAD or RCA 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 Outcome Measures
Name Time Method valvar regurgitation hospital admission through 5 years post-hospitalization valvar regurgitation on MRI core lab read
elevated extracellular volume fraction hospital admission through 5 years post-hospitalization percent with elevated extracellular volume fraction on MRI core lab read
LVSF hospital admission through 5 years post-hospitalization left ventricular (LV) function as measured by left ventricular shortening fraction (LVSF)
Individual z scores for LMCA, RCA and LAD 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
LVEDV z score hospital admission through 5 years post-hospitalization left ventricular (LV) size as measured by left ventricular end-diastolic volume (LVEDV) z score
Qualitative assessment of RV systolic function hospital admission through 5 years post-hospitalization Qualitative assessment of right ventricular (RV) systolic function on core lab echo read
Qualitative assessment of RV global longitudinal strain hospital admission through 5 years post-hospitalization Qualitative assessment, if possible, of right ventricular (RV) global longitudinal strain on core lab echo read
Presence and degree of mitral and aortic regurgitation hospital admission through 5 years post-hospitalization Presence and degree of mitral and aortic regurgitation on echo core lab read
MRI RVEF hospital admission through 5 years post-hospitalization RVEF on MRI core lab read
elevated T2 hospital admission through 5 years post-hospitalization percent with elevated T2 on MRI core lab read
Occurrence of a proximal LAD or RCA z score of ≥2.5 on any echocardiogram 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
Occurrence of aneurysms by Japanese Ministry of Health criteria hospital admission through 5 years post-hospitalization Occurrence of aneurysms by Japanese Ministry of Health criteria applied to core lab echo reads
LVEF hospital admission through 5 years post-hospitalization left ventricular (LV) function as measured by left ventricular ejection fraction (LVEF)
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 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
Presence and size of pericardial effusion hospital admission through 5 years post-hospitalization Presence and size of pericardial effusion on echo core lab read
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 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
MRI LVEF hospital admission through 5 years post-hospitalization LVEF on MRI core lab read
elevated native T1 hospital admission through 5 years post-hospitalization percent with elevated native T1 on MRI core lab read
Maximal vasoactive inotrope score from MIS-C hospital admission to MIS-C hospital discharge Maximal vasoactive inotrope score
LV strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view) 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
Other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic hospital admission through 5 years post-hospitalization percent with other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic
Admission to ICU hospital admission through 5 years post-hospitalization percent with admission to ICU
Symptom duration hospital admission through 5 years post-hospitalization Symptom duration
Global Health - FSS hospital admission through 5 years post-hospitalization Global Health as measured by Functional Status Score \[FSS\]: range 6-30, lower is better
LV diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow 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
myocardial late gadolinium enhancement (LGE) hospital admission through 5 years post-hospitalization percent with and distribution of myocardial late gadolinium enhancement (LGE) on MRI core lab read
abnormal T2-weighted imaging hospital admission through 5 years post-hospitalization percent abnormal T2-weighted imaging on MRI core lab read
coronary artery dilation hospital admission through 5 years post-hospitalization percent with coronary artery dilation on MRI core lab read
CRP hospital admission through 5 years post-hospitalization C-Reactive Protein (CRP) as a laboratory marker of inflammation
Hospital length of stay from MIS-C hospital admission to MIS-C hospital discharge Hospital length of stay
Mortality hospital admission through 5 years post-hospitalization Percent mortality
Global Health - PROMIS 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
CMR abnormal, equivocal, or negative 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
Major medical events 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)
Trial Locations
- Locations (33)
Valley Children's Healthcare and Hospital
🇺🇸Madera, California, United States
Children's Hospital of New Orleans
🇺🇸New Orleans, Louisiana, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Mississippi
🇺🇸Jackson, Mississippi, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of Alabama
🇺🇸Tuscaloosa, Alabama, United States
Children's Hospital of Colorado
🇺🇸Aurora, Colorado, United States
Morgan Stanley Children's Hospital of New York
🇺🇸New York, New York, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
UC San Diego, Rady Children's Hospital
🇺🇸San Diego, California, United States
The Nemours Foundation
🇺🇸Wilmington, Delaware, United States
Chldren's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Children's National Hospital
🇺🇸Washington, D.C., District of Columbia, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
CS Mott Children's Hospital/University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Cohen Children's Medical Center
🇺🇸Queens, New York, United States
Duke Children's Hospital and Health Center
🇺🇸Durham, North Carolina, United States
Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Ann & Robert Lurid Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Riley Children's Hospital
🇺🇸Indianapolis, Indiana, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Children's Medical Center of Dallas - UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Dell Medical Center
🇺🇸Austin, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Baylor /Texas Children's Hospital
🇺🇸Houston, Texas, United States
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin/Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States