COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry

Myocarditis Clinical Trial

— COVID-VIHPR  

Official title:

COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry (COVID-VIHPR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05046002
• Other study ID #: CTO 3740
• Status: Recruiting
• Start date: August 11, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2023
• Source: Ottawa Heart Institute Research Corporation
• Contact: Peter Liu, MD
• Phone: 6136967351
• Email: pliu[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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 three components. First, the vaccine-induced inflammatory heart disease registry will be established. It will include a retrospective cohort study (chart review). Second, patients with persistent symptoms will be invited to participate in additional research-blood work and a 3-month telephone interview, as some of the patients may display chronic symptoms after developing the condition. Third, there will be a prospective, pragmatic design case-control study. We will collect clinical information and include blood samples for biomarkers twice for cases and once for controls and retrospective patients with persistent symptoms. Follow-up telephone interview will be conducted at the 3 months, 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.

Description:

The study will consist of three components. First, the vaccine-induced inflammatory heart disease registry will be established. This will include a retrospective chart review in provinces across Canada. Second, patients with persistent symptoms, identified in the retrospective chart review, will be asked to participate in research bloodwork and phone call follow-ups. Third, there will be a prospective, pragmatic design case-control study.

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. In Ontario, the major hospitals will include CHEO, London, Toronto, Hamilton, and Kingston.

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 research blood samples will be stored and processed at the Ottawa Heart Institute.

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.

For the case-control study, we will establish a surveillance clinic to assess identified controls. The surveillance clinic will evaluate the clinical aspect of controls and assess whether they are at higher risk of developing post-vaccine myocarditis, myopericarditis, or pericarditis. We will draw clinical bloodwork and request a clinical Holter monitor to assess for subclinical myocarditis and arrhythmias. The Holter monitor duration can be determined by local availability, but the goal will be the shortest duration possible, for example 24-48 hrs. We will draw clinical and research bloodwork only once rather than the two time-points in the cases. We will request a research cardiac MRI for the controls to assess for subclinical myocarditis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 31, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

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 In infants and young children, can also have at least two non-specific symptoms within 42 days of receiving a COVID-19 vaccination. These symptoms include irritability, vomiting, poor feeding, tachypnea, or lethargy.

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. a. Elevations in Troponin T, Troponin I, or CK-MB (above threshold of normal)

2. Abnormal MRI (per Brighton Criteria Case Definitions, see Appendix 2 and 3)

3. Any new or worsening cardiac arrhythmias on ECG or telemetry or Holter monitor (per Brighton Criteria Case Definitions, see Appendix 2 and 3) 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.

Related Conditions & MeSH terms

• Heart Diseases
• Myocarditis
• Pericarditis

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with autoimmune disease	To identify how many patients (in each group) have a history of autoimmune disease	30 days
Primary	Composite of MACE	To identify major cardiovascular events - death, ventricular arrhythmia, heart block, heart failure, LV dysfunction (LVEF<55%), cardiac tamponade, re-hospitalization for cardiac reasons	30 days
Secondary	Recurrence of myocarditis/pericarditis	similar symptoms compared to baseline	3 months, 6 months, 12 months, every year for 4 years
Secondary	Atrial arrhythmias	irregular atrial heart rhythms	3 months, 6 months, 12 months, every year for 4 years
Secondary	Cardiovascular mortality	death from any cardiac cause	3 months, 6 months, 12 months, every year for 4 years
Secondary	Quality of life data	EQ-5D-5L questionnaires	3 months, 6 months, 12 months, every year for 4 years