Study type

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness
Disease epidemiology

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Case-control
Cohort
Other
Study drug and medical condition

Study drug International non-proprietary name (INN) or common name

COVID-19 MRNA VACCINE (NUCLEOSIDE-MODIFIED)

Anatomical Therapeutic Chemical (ATC) code

(J07BN01) covid-19, RNA-based vaccine
covid-19, RNA-based vaccine

Medical condition to be studied

Myocarditis
Pericarditis
Population studied

Short description of the study population

For the case-cohort design, individuals with at least one dose of Moderna vaccination targeting SARS-CoV-2 will be used to define a cohort of Moderna vaccination recipients.
Inclusion criteria are at least one year of enrolment in the applicable database prior to the index vaccine dose and without myocarditis events within 6 months prior to receiving a Moderna vaccination targeting SARS-CoV-2.
Cases are those individuals who develop myocarditis or pericarditis any time during the follow-up after Moderna vaccination targeting SARS-CoV-2.
Cases should be able to meet the adjudication criteria according to the Brighton Collaboration Case Definition for possible, probable, or definite myocarditis or pericarditis.
The controls will be sampled from the exposed cohort, such that they align with the distribution of cases based on the month and year of documented Moderna vaccination receipt.
For the cohort design, individuals meeting the criteria of myocarditis or pericarditis, with at least one year of enrolment in the applicable database prior to the index myocarditis or pericarditis event will be included.
Cases of myocarditis and pericarditis will be excluded if these individuals have no record of a Moderna vaccine targeting SARS-CoV-2 but a record of another vaccine targeting SARS-CoV-2 within 30 days prior to the onset of myocarditis or pericarditis.
Within the cohort design, all cases following vaccination are adjudicated according to the Brighton Collaboration Case Definition.
A 1:1 matched sample of the cases not following vaccination matched based on sex and age will also be adjudicated. Only cases that meet the adjudication criteria for possible, probable, or definite myocarditis or pericarditis are included.

Age groups

  • Paediatric Population (< 18 years)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)
      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Estimated number of subjects

6800000
Study design details

Study design

The study will include 2 distinct designs:
- A case-cohort design to assess risk factors for development of post-vaccine myocarditis and pericarditis;
- A cohort design to characterize the clinical course, outcomes, and risk factors for severe myocarditis and pericarditis.

Main study objective

The primary objectives of this study are:
1. To identify possible risk factors for myocarditis and pericarditis following Moderna vaccination targeting SARS-CoV-2, including demographic characteristics, medical history, and vaccination characteristics.
2. To characterize the clinical course of myocarditis and pericarditis of varying origin, including myocarditis and pericarditis associated with Moderna vaccination targeting SARS-CoV-2, and myocarditis or pericarditis not associated with vaccinations targeting SARS-CoV-2, and to identify prognostic factors in the course of myocarditis and pericarditis.

Setting

This study will include information from multiple databases, utilizing routinely collected health and administrative data of four European countries: Denmark, Norway, Spain (2 databases), and the United Kingdom (UK).
The study databases are representative of the source population in each country.

Outcomes

Primary:
1. Risk factors for myocarditis and pericarditis that could potentially include demographics characteristics, lifestyle factors, medical history and vaccination history
2. Clinical outcomes (death, subsequent cardiovascular events, cardiac hospitalizations) after myocarditis or pericarditis

Secondary:
Risk factors for myocarditis and pericarditis, as well as severe myocarditis and pericarditis

Data analysis plan

For the case-cohort analysis, all cases of myocarditis and pericarditis and the full control cohort will be described with respect to demographics, lifestyle factors, medical- and vaccination history.
A conditional logistic regression methodology will be applied to identify potential risk factors for development of myocarditis and pericarditis within the Moderna vaccination targeting SARS-CoV-2-exposed population (Primary objective 1).

To identify differences in clinical course (Primary objective 2) and differences in risk factors (Secondary objective 1) for vaccine associated myocarditis/pericarditis and vaccine unrelated myocarditis/pericarditis, cases in the cohort analysis will be compared based on vaccination status.
Outcomes and follow-up care will also characterized, where feasible.
Standard descriptive statistics will be used to characterise clinical course, outcomes, and long-term outcomes following the initial myocarditis/pericarditis episode.
Cox regression analysis will be utilized to compare the presence of sequelae following myocarditis/pericarditis.