Clinical trial NCT05046002: COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry
Official title: COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry (COVID-VIHPR)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myocarditis
Pericarditis
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2021-09-16
Enrollment: 400
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who have developed symptoms after receiving a COVID-19 vaccine and meet the inclusion and exclusion criteria are eligible to participate in the registry.

Family members, vaccinated in a similar timeframe, with similar technology vaccine (e.g. any mRNA) but did not experience myocarditis side-effects - as a negative controls. If a relative is not available, voluntary controls who received the same type of COVID-19 vaccine in a similar time frame can be recruited (friends, roommates) Alternatively, if family members also had similar reactions, they can be recruited as positive controls.

For the retrospective registry, we would also collect data on COVID-19 myocarditis and pericarditis and all other etiologies of myocarditis or pericarditis.

Brief summary: Myocarditis and pericarditis are inflammatory diseases of the myocardium and pericardium, and can be related to different causes, including vaccines. In the past, some people developed inflammatory heart disease after receiving a live or inactive virus vaccine (smallpox vaccine or flu vaccine). Myocarditis was also seen in people with COVID-19. More recently, many countries reported that some people have developed an inflammatory condition of the myocardium or pericardium after receiving a vaccine for COVID-19.

After the COVID-19 vaccination campaigns, doctors have noticed more people presenting to the Emergency Department with chest pain and shortness of breath after receiving the vaccine, symptoms that resemble myocarditis or pericarditis. These symptoms may start between 2 to 10 days following vaccination and are frequently noticed after the second dose of the vaccines. While pericarditis seems to affect people of various age groups and gender, myocarditis is more commonly seen in young males.

The study will consist of two components. 1) The vaccine-induced inflammatory heart disease database will be established. There will be a retrospective chart review looking at vaccine myocarditis/pericarditis (Brighton Criteria Levels 1-3).

2) There will be a prospective, pragmatic design case-control study for vaccine myocarditis/pericarditis. Follow-up telephone interview will be conducted at 6 months, 12 months and yearly up to 4 years. A record search will also be performed at 6 months, 12 months and yearly for 4 years.

The retrospective component of the study will be conducted by identifying patients previously diagnosed with this condition at participating centres.

Detailed description: The study will consist of two components. 1) The vaccine-induced inflammatory heart disease database will be established. There will be a retrospective chart review looking at vaccine myocarditis/pericarditis (Brighton Criteria Levels 1-3).

2) There will be a prospective, pragmatic design case-control study for vaccine myocarditis/pericarditis.

This will be a multi-center study conducted in centers in Canada that treat post-vaccine inflammatory heart disease in both the inpatient and outpatient settings. Patients will be invited to participate in the Registry when they present to the Emergency Department, during inpatient admission, or in the Cardiology Outpatient Clinic. Patients will be invited to ask a relative or friend to contact the research site to serve as controls. The retrospective component of the study will be conducted by identifying patients previously diagnosed with this condition at participating centers.

At some centers, we will collect clinical information and include blood samples for biomarkers at the baseline/recruitment visit and first follow-up visit for cases and at a research study visit for controls. The follow-up visit is expected to be between 4 and 12 weeks after the initial visit.

The UOHI will see the patients for clinical purposes and the research data will be captured at the same time points. These are expected at baseline/initial visit and then a 4-12-weeks follow-up visit. Clinical assessments and bloodwork will be conducted at the two visits. Subsequent follow-up via telephone interview will be conducted after 6 months, 12 months and every year for 4 years, with a script-based questionnaire to ascertain the patient's clinical status and the achievement of clinical endpoints. Patients will be asked to complete a quality-of-life questionnaire.

Eligibility criteria: Inclusion Criteria:

1. All patients eligible for vaccination with a COVID-19 vaccine,
2. At least one cardiac symptom of suspected myocarditis/pericarditis within 42 days of receiving a COVID-19 vaccination. The clinical symptoms include chest pain, pressure, or discomfort; dyspnea, shortness of breath/dyspnea/pain with breathing, palpitations, diaphoresis, syncope, or sudden death.

   OR At least two non-specific symptoms within 42 days of receiving a COVID-19 vaccination. These symptoms include fatigue, abdominal pain, dizziness or syncope, edema, or cough.

   OR No symptoms, but abnormal histopathology or a combination of abnormal cardiac biomarkers with abnormal cardiac imaging (echo or MRI)
3. At least one of the following:

   1. Elevations in Troponin T, Troponin I, or CK-MB (above threshold of normal)
   2. Abnormal MRI (per Brighton Criteria Case Definitions)
   3. Any new or worsening cardiac arrhythmias on ECG or telemetry or Holter monitor (per Brighton Criteria Case Definitions) including those that normalize on recovery.
   4. Abnormal Echocardiographic findings (per Brighton Criteria Case Definitions, see Appendix 2 and 3)
   5. Physical exam finding: Pericardial friction rub or pulsus paradoxus
   6. Pericardial fluid or inflammation by imaging (echo, MRI, or CT) or at least one of the following elevated biomarkers of inflammation: ESR, CRP, hs-CRP, or D-Dimer.
   7. Enlarged heart on chest radiograph.
   8. Histopathologic examination of myocardial tissue (autopsy or endomyocardial biopsy) showed myocardial inflammation

Exclusion Criteria:

1. Clear alternative diagnosis or explanation for the symptoms and findings (e.g. infectious myocarditis such as Lyme carditis). Note: Work-up of alternative diagnosis is dependent on clinical presentation e.g. Lyme carditis (e.g. endemic area, season, bullseye rash) or autoimmune heart disease (e.g. arthritis, rash, recurrence).
2. Symptoms after 42 days of vaccination.

Primary outcomes:
measure: Proportion of patients with autoimmune disease
timeFrame: 30 days
measure: Composite of MACE
timeFrame: 30 days
Secondary outcomes:
measure: Recurrence of myocarditis/pericarditis
timeFrame: 3 months, 6 months, 12 months, every year for 4 years
measure: Atrial arrhythmias
timeFrame: 3 months, 6 months, 12 months, every year for 4 years
measure: Cardiovascular mortality
timeFrame: 3 months, 6 months, 12 months, every year for 4 years
measure: Quality of life data
timeFrame: 3 months, 6 months, 12 months, every year for 4 years
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Peter Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: