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

Pfizer

Status and phase: Enrolling; Phase 4

Conditions: Myocarditis

Treatments: Diagnostic Test: Cardiac Imaging

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT05295290

C4591036

Details and patient eligibility

About

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.

Full 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).

Enrollment: 300 estimated patients

Sex: All

Ages: Under 20 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

myocarditis/pericarditis following COMIRNATY

Other group

Description:

myocarditis/pericarditis following COMIRNATY within 28 days of dose

Treatment:

Diagnostic Test: Cardiac Imaging

myocarditis/pericarditis following COVID-19 or MIS-C

Other group

Description:

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

Treatment:

Diagnostic Test: Cardiac Imaging