Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children

Multisystem Inflammatory Syndrome in Children (MIS-C) Clinical Trial

— MUSIC  

Official title:

Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05287412
• Other study ID #: G20479
• Status: Active, not recruiting
• Start date: September 30, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Carelon Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

1. Age <21 years.

2. Fever =38°C for =24 hours, or report of subjective fever lasting =24 hours.

3. 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.

4. 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.

5. 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

Related Conditions & MeSH terms

• Multisystem Inflammatory Syndrome in Children (MIS-C)
• Syndrome

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	CS Mott Children's Hospital/University of Michigan	Ann Arbor	Michigan
United States	Chldren's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Dell Medical Center	Austin	Texas
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ann & Robert Lurid Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Medical Center of Dallas - UT Southwestern Medical Center	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke Children's Hospital and Health Center	Durham	North Carolina
United States	Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Baylor /Texas Children's Hospital	Houston	Texas
United States	Riley Children's Hospital	Indianapolis	Indiana
United States	University of Mississippi	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Valley Children's Healthcare and Hospital	Madera	California
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Medical College of Wisconsin/Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	Morgan Stanley Children's Hospital of New York	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Cohen Children's Medical Center	Queens	New York
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	UC San Diego, Rady Children's Hospital	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	University of Alabama	Tuscaloosa	Alabama
United States	Children's National Hospital	Washington	District of Columbia
United States	The Nemours Foundation	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Carelon Research

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	worst-ever LV ejection fraction	worst left ventricular (LV) ejection fraction from core lab echo read during MUSIC study	hospital admission through 5 years post-hospitalization
Primary	worst-ever maximum z score of the proximal LAD or RCA	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	hospital admission through 5 years post-hospitalization
Secondary	Occurrence of a proximal LAD or RCA z score of =2.5 on any echocardiogram	proximal left anterior descending coronary artery (LAD) or right coronary artery (RCA) =2.5 from any core lab echo read	hospital admission through 5 years post-hospitalization
Secondary	Occurrence of aneurysms by Japanese Ministry of Health criteria	Occurrence of aneurysms by Japanese Ministry of Health criteria applied to core lab echo reads	hospital admission through 5 years post-hospitalization
Secondary	Individual z scores for LMCA, RCA and LAD	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	hospital admission through 5 years post-hospitalization
Secondary	LVEDV z score	left ventricular (LV) size as measured by left ventricular end-diastolic volume (LVEDV) z score	hospital admission through 5 years post-hospitalization
Secondary	LVEF	left ventricular (LV) function as measured by left ventricular ejection fraction (LVEF)	hospital admission through 5 years post-hospitalization
Secondary	LVSF	left ventricular (LV) function as measured by left ventricular shortening fraction (LVSF)	hospital admission through 5 years post-hospitalization
Secondary	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	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	hospital admission through 5 years post-hospitalization
Secondary	LV strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view)	left ventricular (LV) strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view) on core lab echo read	hospital admission through 5 years post-hospitalization
Secondary	Qualitative assessment of RV systolic function	Qualitative assessment of right ventricular (RV) systolic function on core lab echo read	hospital admission through 5 years post-hospitalization
Secondary	Qualitative assessment of RV global longitudinal strain	Qualitative assessment, if possible, of right ventricular (RV) global longitudinal strain on core lab echo read	hospital admission through 5 years post-hospitalization
Secondary	Presence and degree of mitral and aortic regurgitation	Presence and degree of mitral and aortic regurgitation on echo core lab read	hospital admission through 5 years post-hospitalization
Secondary	LV diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow	left ventricular (LV) diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow on echo core lab read	hospital admission through 5 years post-hospitalization
Secondary	Presence and size of pericardial effusion	Presence and size of pericardial effusion on echo core lab read	hospital admission through 5 years post-hospitalization
Secondary	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	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
Secondary	MRI LVEF	LVEF on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	MRI RVEF	RVEF on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	valvar regurgitation	valvar regurgitation on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	myocardial late gadolinium enhancement (LGE)	percent with and distribution of myocardial late gadolinium enhancement (LGE) on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	abnormal T2-weighted imaging	percent abnormal T2-weighted imaging on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	elevated T2	percent with elevated T2 on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	elevated native T1	percent with elevated native T1 on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	elevated extracellular volume fraction	percent with elevated extracellular volume fraction on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	coronary artery dilation	percent with coronary artery dilation on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	CMR abnormal, equivocal, or negative	final interpretation of CMR as abnormal, equivocal, or negative (i.e., no abnormal or equivocal findings) on MRI core lab read	hospital admission through 5 years post-hospitalization
Secondary	Other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic	percent with other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic	hospital admission through 5 years post-hospitalization
Secondary	CRP	C-Reactive Protein (CRP) as a laboratory marker of inflammation	hospital admission through 5 years post-hospitalization
Secondary	Admission to ICU	percent with admission to ICU	hospital admission through 5 years post-hospitalization
Secondary	Maximal vasoactive inotrope score	Maximal vasoactive inotrope score	from MIS-C hospital admission to MIS-C hospital discharge
Secondary	Hospital length of stay	Hospital length of stay	from MIS-C hospital admission to MIS-C hospital discharge
Secondary	Symptom duration	Symptom duration	hospital admission through 5 years post-hospitalization
Secondary	Major medical events	percent with major medical events (e.g., stroke, need for extracorporeal therapies such as renal replacement therapy, plasma exchange, ECMO, VAD)	hospital admission through 5 years post-hospitalization
Secondary	Mortality	Percent mortality	hospital admission through 5 years post-hospitalization
Secondary	Global Health - FSS	Global Health as measured by Functional Status Score [FSS]: range 6-30, lower is better	hospital admission through 5 years post-hospitalization
Secondary	Global Health - PROMIS	Global Health as measured by Parent-Reported Outcomes Measurement Information Systems [PROMIS] Instrument: range 7-35, higher is better	hospital admission through 5 years post-hospitalization