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

• ClinicalTrials.gov Identifier: NCT05046002
• Recruitment Status: Recruiting
• First Posted: September 16, 2021
• Last Update Posted: March 15, 2022
• Sponsor: Ottawa Heart Institute Research Corporation
• Information provided by (Responsible Party): Ottawa Heart Institute Research Corporation

Study Description

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.

In the past months, doctors have noticed more people presenting to the Emergency Department with chest pain and shortness of breath after receiving a COVID-19 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.

Condition or disease
Myocarditis; Pericarditis

Detailed 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 province 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. We will not have a standardized management protocol.

This will be a multi-center study conducted in tertiary centers in Canada that treat post-vaccine inflammatory heart disease in both the inpatient and outpatient setting. The study will start at UOHI and The Ottawa Hospital, but expected to rapidly obtain additional sites. 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, either by being approached by a research coordinator or by being provided contact information to call if they are interested. 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.

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. They will be stored for future research in Dr. Peter Liu's Cardiac Function laboratory.

The patients will be followed up in a rapid assessment clinic dedicated to patients with vaccine-induced inflammatory heart disease. Patients at other sites will be followed-up by their respective local site-PIs and bloodwork will be arranged to be sent to the UOHI. Outpatient standard of care clinical cMRI is being expedited by the MRI department for local patients. If an MRI is abnormal, a repeat cardiac MRI will be completed for routine clinical care follow-up.

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 week follow-up visit. Clinical assessments, and bloodwork will be conducted at the two visits. Subsequent follow-up via telephone interview will be conducted at the 3-months, 6 months, 12 months and every year fir 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.

In the event the patient is admitted to the hospital, follow-ups can be completed by a medical record search. Chart reviews will be conducted at 180 days (6 months) and 365 days (1 year) and then annually for up to 4 years.

For the control population- when possible, a family member who has been vaccinated in a similar timeframe with similar technology vaccine (e.g. any mRNA) but did not experience myocarditis side-effects will be invited to participate as a negative control. If a relative is not available, then a voluntary control who has received the same COVID-19 vaccine in a similar time frame can be recruited. Alternatively, if there is a family member who also had similar reactions, they can be recruited to serve as a positive control. 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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 400 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Target Follow-Up Duration: 4 Years
• Official Title: COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry (COVID-VIHPR)
• Actual Study Start Date: August 11, 2021
• Estimated Primary Completion Date: December 30, 2025
• Estimated Study Completion Date: December 31, 2026

Groups and Cohorts

Group/Cohort
Prospective (cases); Patients who develop new symptoms 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, or pain with breathing; palpitations; diaphoresis or sudden death. The symptoms can also be non-specific, including fatigue, abdominal pain, dizziness or syncope, edema, cough or irritability, vomiting, poor feeding, tachypnea or lethargy in young children
Prospective (Control Positive); Family members/relatives who have been vaccinated in a similar timeframe with the participant and had similar reactions
Prospective (Control Negative); Family members/relatives who have been vaccinated in a similar timeframe with the participants but did not experience myocarditis side-effects. If a relative is not available, then a voluntary control who has received the same COVID-19 vaccine in a similar time frame can be recruited.
Retrospective; Identified patients, previously diagnosed with the condition, at participating centers

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with autoimmune disease [ Time Frame: 30 days ]
   To identify how many patients (in each group) have a history of autoimmune disease
2. Composite of MACE [ Time Frame: 30 days ]
   To identify major cardiovascular events - death, ventricular arrhythmia, heart block, heart failure, LV dysfunction (LVEF<55%), cardiac tamponade, re-hospitalization for cardiac reasons

Secondary Outcome Measures :

1. Recurrence of myocarditis/pericarditis [ Time Frame: 3 months, 6 months, 12 months, every year for 4 years ]
   similar symptoms compared to baseline
2. Atrial arrhythmias [ Time Frame: 3 months, 6 months, 12 months, every year for 4 years ]
   irregular atrial heart rhythms
3. Cardiovascular mortality [ Time Frame: 3 months, 6 months, 12 months, every year for 4 years ]
   death from any cardiac cause
4. Quality of life data [ Time Frame: 3 months, 6 months, 12 months, every year for 4 years ]
   EQ-5D-5L questionnaires

Biospecimen Retention:   Samples With DNA

At the time of standard-of-care bloodwork collection, additional research blood samples for biomarker assessment will be collected. Analysis of serum biomarkers such as hs-CRP, ESR, TNF-alpha, IL-1 beta IL-6, and IL-10 may help shed light on the pathway of inflammation. Antibody titres response to mRNA vaccination in younger patients will be of particular interest.

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• 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 a positive controls.

Criteria

Inclusion Criteria:

1. Patients age >= 5 years of age,
2. Developed a new 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, palpitations; diaphoresis or sudden death.

OR Developed two new 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 Developed two new symptoms in infants and young children within 42 days of receiving a COVID-19 vaccination. These symptoms include irritability, vomiting, poor feeding, tachypnea, or lethargy.

3. At least one of the following:

a. Elevations in Troponin I, Troponin T or CK-MB (above threshold of normal) c. Abnormal MRI (per Brighton Criteria Case Definitions) d. Any new or worsening cardiac arrhythmias on ECG or telemetry or Holter monitor (per Brighton Criteria Case Definitions), including those that normalize on recovery e. Abnormal echocardiographic findings (per Brighton Criteria Case Definitions) f. Pericardial friction rub or pulsus paradoxus on physical exam g. Pericardial fluid or inflammation by imaging (echo, MRI or CT) h. At least one of the following elevated biomarkers of inflammation: ESR, CRP, hs-CRP or D-Dimer i. Enlarged heart on chest radiograph

Exclusion Criteria:

1. Clear alternative diagnosis or explanation for the symptoms and findings such as active COVID-19 infection.

Contacts and Locations

Contacts

Contact: Peter Liu, MD; 6136967351; pliu@ottawaheart.ca

Contact: Ermina Moga; 6136967000 ext 10945; emoga@ottawaheart.ca

Locations

Canada, Ontario

University of Ottawa Heart Institute; Recruiting

Ottawa, Ontario, Canada, K1Y4W7

Contact: Tahir Kafil, MD 6136967327 tkafil@ottawaheart.ca

Contact: Peter Liu, MD 6136967351 pliu@ottawaheart.ca

Sponsors and Collaborators

Ottawa Heart Institute Research Corporation

Investigators

• Principal Investigator: Peter Liu, MD; Ottawa Heart Institute Research Corporation

More Information

• Responsible Party: Ottawa Heart Institute Research Corporation
• ClinicalTrials.gov Identifier: NCT05046002
• Other Study ID Numbers: CTO 3740
• First Posted: September 16, 2021
• Last Update Posted: March 15, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: To be determined

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Heart Diseases; Myocarditis; Pericarditis; Cardiovascular Diseases; Cardiomyopathies