Clinical trial NCT05287412: Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children
Official title: Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Multisystem Inflammatory Syndrome in Children (MIS-C)
Keywords: COVID
Lead sponsor: Carelon Research
Sponsor class: OTHER
First posted: 2022-03-18
Enrollment: 1200
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: children and young adults \<21 years with Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) at a participating hospital

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.

Eligibility criteria: 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

Primary outcomes:
measure: worst-ever LV ejection fraction
timeFrame: hospital admission through 5 years post-hospitalization
measure: worst-ever maximum z score of the proximal LAD or RCA
timeFrame: hospital admission through 5 years post-hospitalization
Secondary outcomes:
measure: Occurrence of a proximal LAD or RCA z score of ≥2.5 on any echocardiogram
timeFrame: hospital admission through 5 years post-hospitalization
measure: Occurrence of aneurysms by Japanese Ministry of Health criteria
timeFrame: hospital admission through 5 years post-hospitalization
measure: Individual z scores for LMCA, RCA and LAD
timeFrame: hospital admission through 5 years post-hospitalization
measure: LVEDV z score
timeFrame: hospital admission through 5 years post-hospitalization
measure: LVEF
timeFrame: hospital admission through 5 years post-hospitalization
measure: LVSF
timeFrame: hospital admission through 5 years post-hospitalization
measure: 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
timeFrame: hospital admission through 5 years post-hospitalization
measure: LV strain (global longitudinal strain from apical view and global circumferential strain from parasternal short-axis view)
timeFrame: hospital admission through 5 years post-hospitalization
measure: Qualitative assessment of RV systolic function
timeFrame: hospital admission through 5 years post-hospitalization
measure: Qualitative assessment of RV global longitudinal strain
timeFrame: hospital admission through 5 years post-hospitalization
measure: Presence and degree of mitral and aortic regurgitation
timeFrame: hospital admission through 5 years post-hospitalization
measure: LV diastolic function, i.e., tissue Doppler imaging and mitral valve (MV) inflow
timeFrame: hospital admission through 5 years post-hospitalization
measure: Presence and size of pericardial effusion
timeFrame: hospital admission through 5 years post-hospitalization
measure: 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
timeFrame: 3 months post-discharge
measure: MRI LVEF
timeFrame: hospital admission through 5 years post-hospitalization
measure: MRI RVEF
timeFrame: hospital admission through 5 years post-hospitalization
measure: valvar regurgitation
timeFrame: hospital admission through 5 years post-hospitalization
measure: myocardial late gadolinium enhancement (LGE)
timeFrame: hospital admission through 5 years post-hospitalization
measure: abnormal T2-weighted imaging
timeFrame: hospital admission through 5 years post-hospitalization
measure: elevated T2
timeFrame: hospital admission through 5 years post-hospitalization
measure: elevated native T1
timeFrame: hospital admission through 5 years post-hospitalization
measure: elevated extracellular volume fraction
timeFrame: hospital admission through 5 years post-hospitalization
measure: coronary artery dilation
timeFrame: hospital admission through 5 years post-hospitalization
measure: CMR abnormal, equivocal, or negative
timeFrame: hospital admission through 5 years post-hospitalization
measure: Other organ abnormalities by medical history: Immunologic, rheumatologic, renal, pulmonary, hematologic, gastrointestinal, dermatologic or neurologic
timeFrame: hospital admission through 5 years post-hospitalization
measure: CRP
timeFrame: hospital admission through 5 years post-hospitalization
measure: Admission to ICU
timeFrame: hospital admission through 5 years post-hospitalization
measure: Maximal vasoactive inotrope score
timeFrame: from MIS-C hospital admission to MIS-C hospital discharge
measure: Hospital length of stay
timeFrame: from MIS-C hospital admission to MIS-C hospital discharge
measure: Symptom duration
timeFrame: hospital admission through 5 years post-hospitalization
measure: Major medical events
timeFrame: hospital admission through 5 years post-hospitalization
measure: Mortality
timeFrame: hospital admission through 5 years post-hospitalization
measure: Global Health - FSS
timeFrame: hospital admission through 5 years post-hospitalization
measure: Global Health - PROMIS
timeFrame: hospital admission through 5 years post-hospitalization
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Valley Children's Healthcare and Hospital
state: California
city: San Diego
country: United States
facility: UC San Diego, Rady Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Wilmington
country: United States
facility: The Nemours Foundation
state: Delaware
city: Washington, D.C.
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Chldren's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert Lurid Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: New Orleans
country: United States
facility: Children's Hospital of New Orleans
state: Louisiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: CS Mott Children's Hospital/University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York
state: New York
city: Queens
country: United States
facility: Cohen Children's Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Children's Hospital and Health Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Dell Medical Center
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center of Dallas - UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor /Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Children's Hospital of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
References: