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

LOW INTERVENTIONAL COHORT STUDY OF MYOCARDITIS/PERICARDITIS ASSOCIATED WITH COMIRNATY IN PERSONS LESS THAN 21 YEARS OF AGE

The purpose of this study is to learn about the safety and effects of the vaccine (called COMIRNATY) for the potential prevention of COVID-19. This study is seeking participants who:

1. Are age <21 years.
2. Have presentation to participating medical center with evaluation in Emergency Room and/or hospitalization.
3. Received any dose(s) of COMIRNATY within 21 days of symptom onset.
4. Meet criteria of Centers for Disease Control and Prevention case definition of probable or confirmed myocarditis/pericarditis
5. 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Myocarditis
• Intervention / Treatment: Diagnostic test: Cardiac Imaging

Detailed Description

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 ≤ 21 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. Cohort 3 participants will not be stratified by MIS-C diagnosis because of the rarity of myocardial involvement in children with acute severe COVID-19

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 200 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).

• Study Type: Interventional
• Enrollment (Actual): 319
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • Madera, California, United States, 93636
      • Valley Children's Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Childrens National Hospital
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta - Arthur M. Blank Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at IU Health
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Center
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Childrens Mercy Kansas City
  • New York
    • New Hyde Park, New York, United States, 11042
      • Northwell Health-Cohen Children's Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • South Carolina
    • North Charleston, South Carolina, United States, 20406
      • MUSC Summey Medical Pavilion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cohort 1/2:

  1. Age <21 years.
  2. Presentation to participating medical center with evaluation in Emergency Room and/or hospitalization.
  3. Received any dose(s) of COMIRNATY within 21 days of symptom onset.
  4. Meets criteria of Centers for Disease Control and Prevention case definition of probable or confirmed myocarditis/pericarditis
  5. 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:

  1. Age <21 years.
  2. Presentation to participating medical center with evaluation in Emergency Room and/or hospitalization.

  3. COVID-19-related disease

     1. Acute COVID-19 infection OR
     2. Multi-system Inflammatory Syndrome in Children Associated with COVID-19 (MIS-C) AND

  4. Probable or confirmed myocarditis/pericarditis* not temporally related to vaccination with COMINARTY

     1. 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

     2. Confirmed myocarditis/pericarditis as defined by:

        • Histopathologic confirmation of myocarditis OR
        • Elevated troponin above upper limit of normal AND cMRI findings consistent with myocarditis
  5. 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:

1. 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.

2. 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:

   1. Bicommissural aortic valve with < trivial stenosis and/or insufficiency
   2. Mitral valve prolapse with < trivial insufficiency
   3. Hemodynamically insignificant atrial septal or ventricular septal defects.
3. Previous administration with an investigational drug or vaccine within 30 days of enrollment (or as determined by the local requirement).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Other: myocarditis/pericarditis following COMIRNATY; myocarditis/pericarditis following COMIRNATY within 21 days of dose	Diagnostic test: Cardiac Imaging; ECG, echocardiogram, ambulatory monitor, exercise stress test

What is the study measuring?

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
Complications, including non-cardiac morbidities by medical history		Up to 5 years following illness onset.
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.
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.
Freedom from the primary study endpoint ((The Primary Study Endpoint is the Composite Findings of Myocarditis and is described in Outcome Measure 1).	Measurement Schedule and Type of Assessment: Echocardiography: 2 weeks, 6 weeks, 6 months , and 1-5 years;; cMRI: If ordered for routine clinical care, 6 months; annually at 1-5 years if previous study was abnormal;; Exercise stress testing by 6 months; annually at 1-5 years if previous study was abnormal	2 weeks, 6 weeks, 6 months, and 1-5 years
Time to recovery (return to normal) from the presence of abnormal LV strain parameters on echocardiography among those who had abnormalities at baseline		2 weeks, 6 weeks, 6 months, and 1-5 years

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Carelon Research
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Estimated): April 2, 2029
• Study Completion (Estimated): April 2, 2029

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: COVID-19; MIS-C; COMIRNATY; post-vaccine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Cardiomyopathies; COVID-19; Myocarditis
• Other Study ID Numbers: C4591036; NCT05295290 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No