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| Name | Class |
|---|---|
| The Swedish Heart and Lung Association | OTHER |
| Örebro University, Sweden | OTHER |
| University of Cambridge | OTHER |
| Aarhus University Hospital |
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The goal of this randomized, double-blind, placebo-controlled clinical trial is to investigate the immunological effects of influenza vaccination outside of the influenza season on arterial inflammation in patients with a recent acute myocardial infarction (AMI). The primary objective is to compare the effects of influenza vaccination to those of a placebo in reducing post-myocardial infarction coronary inflammation as measured by coronary computed tomography angiography (CCTA). The main questions it aims to answer are:
Does influenza vaccination reduce arterial inflammation as measured by CCTA at week 8 after percutaneous coronary intervention (PCI) in comparison to baseline? Does influenza vaccination modulate systemic inflammation as measured by blood biomarkers and in-vitro challenge tests at week 8 after PCI in comparison to baseline? Researchers will compare the effects of influenza vaccination with those of a placebo.
Following informed consent patients are randomized in a 1:1 fashion to influenza vaccination or placebo up to 7 days following PCI. Blood tests for immune cell phenotyping and transcriptomic and proteomic analyses will be collected at baseline and 8 weeks after study inclusion. Patients will undergo CTCA at baseline (≤ 7 days of an AMI) and 8 weeks after PCI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vaccination arm | Active Comparator | Influenza vaccine (Inactivated, split virus or surface antigen Suspension for injection, prefilled syringe ATC code: J07BB02) |
|
| Placebo arm | Placebo Comparator | Sodium Chloride (Placebo) Solution for infusion, 9mg/ml ATC code: B05BB01 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Influenza vaccine | Biological | Inactivated, split virus or surface antigen Suspension for injection, prefilled syringe ATC code: J07BB02 |
|
| Measure | Description | Time Frame |
|---|---|---|
| The right coronary artery | Primary endpoint definition is a difference in pericoronary adipose tissue density (perivascular fat attenuation index) around the right coronary artery (RCA) measured by repeated CCTA imaging | Between baseline and 8 weeks follow up. |
| Measure | Description | Time Frame |
|---|---|---|
| The whole coronary tree | Change from baseline in the average pericoronary adipose tissue density of the whole coronary tree (main epicardial arteries ≥2mm). | Between baseline and 8 weeks follow up. |
| Ascending aorta |
| Measure | Description | Time Frame |
|---|---|---|
| Explorative endpoints | Differences in peripheral blood immune cell signatures measured by mass cytometry (CyTOF), and proteomics (O-link) will be assessed in a subset of patients with and without reduction in coronary inflammation, measured by perivascular adipose tissue density on CCTA . Single cell RNA sequencing (sRNAseq) and measurements of cytokine profiles after in-vitro stimulation of peripheral blood mononuclear cells (PBMCs) will be performed in a subgroup of patients |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sara Cajander, MD | Contact | +46196021042 | +46196021000 | sara.cajander@oru.se |
| Name | Affiliation | Role |
|---|---|---|
| Sara Cajander, MD | Region Örebro län | Principal Investigator |
| Ole Frøbert, professor | Region Örebro län | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital, Department of Cardiology | Recruiting | Aarhus | DK-8200 | Denmark |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| OTHER |
| Cambridge University Hospitals NHS Foundation Trust | OTHER |
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| Placebo | Biological | Sodium Chloride Solution for infusion, 9mg/ml ATC code: B05BB01 |
|
Change from baseline in the perivascular adipose tissue density of the ascending aorta
| Between baseline and 8 weeks follow up. |
| Interleukin 1 beta (IL-1β) | Difference in peripheral blood IL-1β concentrations | Between baseline and 8 weeks follow up. |
| Tumor necrosis factor alpha (TNF-α) | Difference in peripheral blood TNF-α concentrations | Between baseline and 8 weeks follow up. |
| Interleukin-2 receptor (IL-2r) | Difference in peripheral blood IL-2r concentrations | Between baseline and 8 weeks follow up. |
| Interleukin Interleukin-6 (IL-6 ) | Difference in peripheral blood IL-6 concentrations | Between baseline and 8 weeks follow up. |
| Ferritin | Difference in peripheral blood ferritin concentrations | Between baseline and 8 weeks follow up. |
| Troponin-I | Differences in peripheral blood troponin-I concentrations between study groups | At 8 weeks follow up. |
| N-terminal pro-B-type natriuretic peptide | Differences in peripheral blood N-terminal pro-B-type natriuretic peptide concentrations between study groups | At 8 weeks follow up. |
| 8 weeks follow up |
| Explorative endpoints | Exploratory proteomics by (O-link) from day 0 sampling will be performed in the whole study population to identify early biomarkers for prediction of residual inflammation. | Baseline |
| Örebro University Hospital | Recruiting | Örebro | 70185 | Sweden |
|
| Cambridge University Hospitals NHS Foundation Trust | Recruiting | Cambridge | CB2 0QQ | United Kingdom |
|
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |