A Study to Learn About The COVID-19 (Study) Vaccine (Called COMIRNATY) in People That Are Less Than 21 Years Old.

Study Overview
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Brief Summary
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The purpose of this clinical trial is to learn about the safety and effects of the study vaccine (called COMIRNATY) for the potential prevention of COVID-19. This study is seeking participants who: Are age <21 years. Have presentation to participating medical center with evaluation in Emergency Room and/or hospitalization. Received either the 1st, 2nd, 3rd or booster dose(s) of COMIRNATY within 7 days of symptom onset. Meet criteria of Centers for Disease Control and Prevention case definition of probable or confirmed myocarditis/pericarditis Are capable of giving signed informed consent/assent (by parents/legal guardians of minors and/or patients), which includes compliance with the requirements and restrictions listed in the Informed Consent/Assent Document and in this protocol OR meets criteria for waiver of consent. This study will examine the potential long-term effects associated with myocarditis/pericarditis following vaccination with COMIRNATY. The association of myocarditis/pericarditis in participants who received the study vaccine (COMIRNATY) compared with those associated with COVID-19 will also be examined. This will help us determine if COMIRNATY is safe and effective, and if there is a myocarditis/pericarditis association that should be noted. Participants will take part in this study for up to 5 years. During this time, they will receive complete cardiac imaging tests, and have follow up visits per guidance stated in the study protocol.

Detailed Description
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This is a low-interventional cohort study to determine cardiac and non-cardiac long-term outcomes of persons <21 years of age with myocarditis/pericarditis after the administration of COMIRNATY, compared with similarly aged persons with myocarditis/pericarditis associated with COVID-19, including MIS-C. To be classified as having COMIRNATY-associated myocarditis/pericarditis, a person must 1) meet the CDC case definition for probable or confirmed myocarditis/pericarditis, 2) have received any dose of COMIRNATY ≤ 7 days of symptom onset, and 3) have no other plausible alternative etiology at the time of enrollment. To be classified as having myocarditis/pericarditis associated with COVID-19, a person must have 1) either acute severe COVID-19 infection or MIS-C, as defined by the CDC, 2) findings of probable or confirmed myocarditis in the CDC definition, 3) no other plausible alternative etiology. A description of the three cohorts is as follows: Cohort 1: Prospectively ascertained cases of probable or confirmed myocarditis/pericarditis associated with COMIRNATY , i.e., participants enrolled under protocol during hospitalization or </= 2 weeks of hospital discharge. Cohort 2: Retrospectively ascertained cases of probable or confirmed myocarditis/pericarditis associated with COMIRNATY , i.e., participants enrolled > 2 weeks after hospital discharge. Participants can be retrospectively ascertained and enrolled at any time from their COMIRNATY-associated myocarditis/pericarditis. Cohort 3: Comparator cohort of COVID-19- related myocarditis/pericarditis , including MIS-C, both retrospectively and prospectively ascertained, and enrolled at any time from their COVID-19 or MIS-C associated myocarditis/pericarditis diagnosis. Participants in all cohorts will be those who present to participating medical centers for care. This study is a collaboration between the National Heart, Lung, and Blood Institute (NHLBI)'s Pediatric Heart Network (PHN) and Pfizer. Enrollment will include approximately 300 prospectively and retrospectively ascertained cases of children, adolescents, and young adults <21 years of age who receive care for myocarditis/pericarditis associated with COMIRNATY (Cohort 1 and 2); and approximately 100 persons <21 years of age with COVID -19-associated myocarditis/pericarditis, including MIS-C (Cohort 3).

Official Title
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Low Interventional Cohort Study of Myocarditis/Pericarditis Associated With COMIRNATY in Persons Less Than 21 Years of Age

Conditions
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Myocarditis

Intervention / Treatment
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* Diagnostic Test: Cardiac Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1/2: Age <21 years. Presentation to participating medical center with evaluation in Emergency Room and/or hospitalization. Received either the 1st, 2nd, 3rd or booster dose(s) of COMIRNATY within 28 days of symptom onset. Meets criteria of Centers for Disease Control and Prevention case definition of probable or confirmed myocarditis/pericarditis Capable of giving signed informed consent/assent (by parents/legal guardians of minors and/or patients), which includes compliance with the requirements and restrictions listed in the Informed Consent/Assent Document and in this protocol OR meets criteria for waiver of consent. Cohort 3: Age <21 years. Presentation to participating medical center with evaluation in Emergency Room and/or hospitalization. COVID-19-related disease Acute COVID-19 infection OR Multi-system Inflammatory Syndrome in Children Associated with COVID-19 (MIS-C) AND Probable or confirmed myocarditis/pericarditis* not temporally related to vaccination with COMINARTY Probable myocarditis/pericarditis as defined by ≥ 1 new finding of: Elevated troponin above upper limit of normal Abnormal ECG or rhythm monitoring finding consistent with myocarditis Abnormal cardiac function or wall motion abnormalities on echocardiogram cMRI findings consistent with myocarditis OR Confirmed myocarditis/pericarditis as defined by: Histopathologic confirmation of myocarditis OR Elevated troponin above upper limit of normal AND cMRI findings consistent with myocarditis Capable of giving signed informed consent/assent (by parents/legal guardians of minors and/or patients), which includes compliance with the requirements and restrictions listed in the Informed Consent/Assent Document and in this protocol OR meets criteria for waiver of consent. Exclusion Criteria: A plausible alternative etiology for myocarditis/pericarditis, as determined by the site based upon their routine clinical practice for evaluation of potential causes for myocarditis/pericarditis. Pre-existing cardiac conditions that could impact the primary endpoint, including but not limited to, documented history of left ventricular dysfunction (e.g., cardiomyopathy or myocardial infarction), pacemaker, or congenital heart disease, with the exceptions of: Bicommissural aortic valve with < trivial stenosis and/or insufficiency Mitral valve prolapse with < trivial insufficiency Hemodynamically insignificant atrial septal or ventricular septal defects. Previous administration with an investigational drug or vaccine within 30 days of enrollment (or as determined by the local requirement).

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: myocarditis/pericarditis following COMIRNATY<br>myocarditis/pericarditis following COMIRNATY within 28 days of dose | Diagnostic Test: Cardiac Imaging<br>* ECG, echocardiogram, ambulatory monitor, exercise stress test<br>|
| Other: myocarditis/pericarditis following COVID-19 or MIS-C<br>myocarditis/pericarditis following COVID-19 or MIS-C without exposure to COMIRNATY | Diagnostic Test: Cardiac Imaging<br>* ECG, echocardiogram, ambulatory monitor, exercise stress test<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite findings of myocarditis | This is a single composite primary outcome measure. This primary composite study endpoint is defined as the presence of 1 or more of the following 6 months after illness onset: left ventricular dysfunction (LVEF < 55% by echocardiogram), findings of myocarditis by original or revised Lake Louise criteria on cardiac MRI, or the presence of high-grade arrhythmia or conduction system disturbance on ECG or ambulatory monitoring. | 6 months after illness onset | 
| Left ventricular ejection fraction (LVEF) < 55% by echocardiography |  | Up to 5 years following illness onset. | 
| Myocarditis by original or revised Lake Louise criteria on cMRI |  | Up to 5 years following illness onset. | 
| Arrhythmias on cardiac recording (ECG, ambulatory monitoring) |  | Up to 5 years following illness onset. | 
| Complications, including non-cardiac morbidities by medical history |  | Up to 5 years following illness onset. | 
| Functional Status by Behavior Assessment System for Children, Third Edition BASC-3 or PROMIS Short Forms | Behavior Assessment System for Children, Third Edition (BASC-3), <8 yr (T score <30->70 with higher number meaning lower functioning) or PROMIS Short Forms ≥8 yr (scores from 3-15 with higher number meaning better functioning) | Up to 5 years following illness onset. | 
| The Pediatric Quality of Life Inventory (PEDS QL) | The 27 question, age-appropriate and parent-proxy questionnaires, will be used in 2 to <18-year-old participants to assess quality of life. Scores span 0-108 with higher number being better functioning. | Up to 5 years following illness onset. | 
| The Quality of Life Scale (QOLS) | The QOLS, a 16-item self-report form that assesses overall quality of life on a scale of 16-112 (higher scores indicate better quality of life) will be administered for participants ≥18 years old. | Up to 5 years following illness onset. | 
| Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring) |  | Up to 5 years following illness onset. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular ejection fraction (LVEF) by echocardiogram as a measure of myocardial performance. |  | During the hospitalization or within 2 weeks of hospital discharge, generally obtained less than 3 weeks from presentation. | 
| Time to recovery of myocardial inflammation and injury by Lake Louise (the original or revised) criteria |  | During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation | 
| Arrhythmias on cardiac recording (ECG, ambulatory monitoring) |  | During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation | 
| Complications, including non-cardiac morbidities for myocarditis |  | During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation | 
| Echocardiographic LVEF |  | Up to 5 years following illness onset. | 
| Myocardial inflammation scarring (by cMRI) |  | Up to 5 years following illness onset. | 
| Arrhythmias on cardiac recordings |  | Up to 5 years following illness onset. | 
| Complications, including non-cardiac morbidities by medical history |  | Up to 5 years following illness onset. | 
| Lower LVEF by composite results | Identification of possible sociodemographic and medical risk factors for greater frequency and severity of acute and longer-term cardiac sequelae in participants, measured by ECG, original or revised Lake Louise criteria on cMRI, and presence of high-grade arrhythmia or conduction system disturbance on ECG or ambulatory monitoring. | Up to 5 years following illness onset. | 
| For patients with isolated pericarditis, to determine time to recovery to normal. | Freedom from symptoms/signs of pericarditis; typical ECG findings of pericarditis; >small pericardial effusion; therapy with anti-inflammatory medications | At each study visit, up to 5 years, until the endpoint event is met | 
| Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring) |  | During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation | 
| Conduction system disturbances on cardiac recordings |  | Up to 5 years following illness onset. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MIS-C, COMIRNATY, post-vaccine, COVID-19