Clinical trial NCT05295290: A Study to Learn About The COVID-19 (Study) Vaccine (Called COMIRNATY) in People That Are Less Than 21 Years Old.
Official title: Low Interventional Cohort Study of Myocarditis/Pericarditis Associated With COMIRNATY in Persons Less Than 21 Years of Age
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Myocarditis
Keywords: COMIRNATY
post-vaccine
COVID-19
MIS-C
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Carelon Research
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-03-25
Enrollment: 300
Sex: ALL
Minimum age (years): 0
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.

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 ≤ 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).

Eligibility criteria: 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).

Primary outcomes:
measure: Composite findings of myocarditis
timeFrame: 6 months after illness onset
measure: Left ventricular ejection fraction (LVEF) < 55% by echocardiography
timeFrame: Up to 5 years following illness onset.
measure: Myocarditis by original or revised Lake Louise criteria on cMRI
timeFrame: Up to 5 years following illness onset.
measure: Arrhythmias on cardiac recording (ECG, ambulatory monitoring)
timeFrame: Up to 5 years following illness onset.
measure: Complications, including non-cardiac morbidities by medical history
timeFrame: Up to 5 years following illness onset.
measure: Functional Status by Behavior Assessment System for Children, Third Edition BASC-3 or PROMIS Short Forms
timeFrame: Up to 5 years following illness onset.
measure: The Pediatric Quality of Life Inventory (PEDS QL)
timeFrame: Up to 5 years following illness onset.
measure: The Quality of Life Scale (QOLS)
timeFrame: Up to 5 years following illness onset.
measure: Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring)
timeFrame: Up to 5 years following illness onset.
Secondary outcomes:
measure: Left ventricular ejection fraction (LVEF) by echocardiogram as a measure of myocardial performance.
timeFrame: During the hospitalization or within 2 weeks of hospital discharge, generally obtained less than 3 weeks from presentation.
measure: Time to recovery of myocardial inflammation and injury by Lake Louise (the original or revised) criteria
timeFrame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
measure: Arrhythmias on cardiac recording (ECG, ambulatory monitoring)
timeFrame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
measure: Complications, including non-cardiac morbidities for myocarditis
timeFrame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
measure: Echocardiographic LVEF
timeFrame: Up to 5 years following illness onset.
measure: Myocardial inflammation scarring (by cMRI)
timeFrame: Up to 5 years following illness onset.
measure: Arrhythmias on cardiac recordings
timeFrame: Up to 5 years following illness onset.
measure: Complications, including non-cardiac morbidities by medical history
timeFrame: Up to 5 years following illness onset.
measure: Lower LVEF by composite results
timeFrame: Up to 5 years following illness onset.
measure: For patients with isolated pericarditis, to determine time to recovery to normal.
timeFrame: At each study visit, up to 5 years, until the endpoint event is met
measure: Conduction system disturbances on cardiac recording (ECG, ambulatory monitoring)
timeFrame: During hospitalization or within 2 weeks of hospital discharge, commonly less than 3 weeks from presentation
measure: Conduction system disturbances on cardiac recordings
timeFrame: Up to 5 years following illness onset.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: Aurora
country: United States
facility: Childrens Hospital of Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Nemours Children's Hospital, Delaware
state: Delaware
city: Washington
country: United States
facility: Childrens National Hospital
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: New Orleans
country: United States
facility: Children's Hospital
state: Louisiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital-Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Children'S Hospitals & Clinics of Minn
state: Minnesota
city: Kansas City
country: United States
facility: Childrens Mercy Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Hyde Park
country: United States
facility: Northwell Health-Cohen Children's Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
state: South Carolina
city: Houston
country: United States
facility: 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: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: