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

Myocarditis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05295290
• Other study ID #: C4591036
• Status: Recruiting
• Phase: Phase 4
• Start date: November 21, 2022
• Est. completion date: November 21, 2030

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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: 1. Are age <21 years. 2. Have presentation to participating medical center with evaluation in Emergency Room and/or hospitalization. 3. Received either the 1st, 2nd, 3rd or booster dose(s) of COMIRNATY within 7 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.

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 ≤ 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 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: November 21, 2030
• Est. primary completion date: November 21, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 20 Years

Eligibility

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 either the 1st, 2nd, 3rd or booster dose(s) of COMIRNATY within 28 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).

Related Conditions & MeSH terms

• Myocarditis

Intervention

Diagnostic Test:
• Cardiac Imaging
ECG, echocardiogram, ambulatory monitor, exercise stress test

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Hospital-Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Childrens Hospital of Colorado	Aurora	Colorado
United States	Children's of Alabama	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina (Musc) - Children's Hospital	Charleston	South Carolina
United States	Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital	Charleston	South Carolina
United States	Lurie Children's Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke University Hospital	Durham	North Carolina
United States	Duke University Hospital	Durham	North Carolina
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Baylor College Of Medicine (Bcm) - Texas Children's Hospital (Tch)	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Childrens Mercy Kansas City	Kansas City	Missouri
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Valley Children's Hospital	Madera	California
United States	Northwell Health-Cohen Children's Medical Center	New Hyde Park	New York
United States	Children's Hospital	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Lucile Packard Children's Hospital Stanford	Palo Alto	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Primary Children's	Salt Lake City	Utah
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Seattle Children's Hospital & Research Institute	Seattle	Washington
United States	Childrens National Hospital	Washington	District of Columbia
United States	Nemours Children's Hospital, Delaware	Wilmington	Delaware

Sponsors (3)

Lead Sponsor	Collaborator
Pfizer	Carelon Research, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Left ventricular ejection fraction (LVEF) < 55% by echocardiography		Up to 5 years following illness onset.
Primary	Myocarditis by original or revised Lake Louise criteria on cMRI		Up to 5 years following illness onset.
Primary	Arrhythmias on cardiac recording (ECG, ambulatory monitoring)		Up to 5 years following illness onset.
Primary	Complications, including non-cardiac morbidities by medical history		Up to 5 years following illness onset.
Primary	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.
Primary	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.
Primary	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.
Primary	Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring)		Up to 5 years following illness onset.
Secondary	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.
Secondary	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
Secondary	Arrhythmias on cardiac recording (ECG, ambulatory monitoring)		During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
Secondary	Complications, including non-cardiac morbidities for myocarditis		During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
Secondary	Echocardiographic LVEF		Up to 5 years following illness onset.
Secondary	Myocardial inflammation scarring (by cMRI)		Up to 5 years following illness onset.
Secondary	Arrhythmias on cardiac recordings		Up to 5 years following illness onset.
Secondary	Complications, including non-cardiac morbidities by medical history		Up to 5 years following illness onset.
Secondary	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.
Secondary	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
Secondary	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
Secondary	Conduction system disturbances on cardiac recordings		Up to 5 years following illness onset.

External Links

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