Study of Myo/Pericarditis Associated With COMIRNATY (Vaccine to Prevent COVID-19) in Persons <21 Years of Age

Sponsor

Pfizer (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05295290

Collaborator

HealthCore-NERI (Other)

300

Enrollment

Locations

Arms

Anticipated Duration (Months)

150

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary aim of this low interventional cohort study is to characterize the potential long-term sequelae associated with myocarditis/pericarditis following vaccination with COMIRNATY, compared with associated myocarditis/pericarditis following COVID-19 in persons <21 years old, with up to 5 years of follow-up.

Condition or Disease	Intervention/Treatment	Phase
Myocarditis	Diagnostic Test: Cardiac Imaging	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

This is a low-interventional cohort study to determine cardiac and non-cardiac long-term outcomes of persons less than 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, without exposure to COMIRNATY.

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Jul 18, 2022

Anticipated Primary Completion Date :

Jul 16, 2028

Anticipated Study Completion Date :

Jul 16, 2028

Arms and Interventions

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

Arm

Intervention/Treatment

Other: myocarditis/pericarditis following COMIRNATY

myocarditis/pericarditis following COMIRNATY within 28 days of dose

Diagnostic Test: Cardiac Imaging

ECG, echocardiogram, ambulatory monitor, exercise stress test

Other: myocarditis/pericarditis following COVID-19 or MIS-C

myocarditis/pericarditis following COVID-19 or MIS-C without exposure to COMIRNATY

Diagnostic Test: Cardiac Imaging

ECG, echocardiogram, ambulatory monitor, exercise stress test

Outcome Measures

Primary Outcome Measures

Composite findings of myocarditis [6 months after illness onset]
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.
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 [Up to 5 years following illness onset.]
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)
The Pediatric Quality of Life Inventory (PEDS QL) [Up to 5 years following illness onset.]
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.
The Quality of Life Scale (QOLS) [Up to 5 years following illness onset.]
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.
Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring) [Up to 5 years following illness onset.]

Secondary Outcome Measures

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 [Up to 5 years following illness onset.]
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.
For patients with isolated pericarditis, to determine time to recovery to normal. [At each study visit, up to 5 years, until the endpoint event is met]
Freedom from symptoms/signs of pericarditis; typical ECG findings of pericarditis; >small pericardial effusion; therapy with anti-inflammatory medications
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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).