Acute Myocardial Infarction, Cardiovascular Diseases, Inflammatory Response
Conditions
Keywords
Coronary computed tomography angiography, Percutaneous coronary intervention, Influenza vaccine, Non ST-segment elevation myocardial infarction
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALInfluenza vaccine
Inactivated, split virus or surface antigen Suspension for injection, prefilled syringe ATC code: J07BB02
BIOLOGICALPlacebo
Sodium Chloride Solution for infusion, 9mg/ml ATC code: B05BB01
Sponsors
Region Örebro County
The Swedish Heart and Lung Association
Örebro University, Sweden
University of Cambridge
Aarhus University Hospital
Cambridge University Hospitals NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of non-ST-segment elevation myocardial infarction * A finalized coronary PCI * Male or non-fertile female subjects ≥18 years. (Females without childbearing potential, postmenopausal women and women with a history of hysterectomy or other medical conditions that preclude pregnancy) * Written informed consent * A CCTA can be scheduled within 7 days after PCI
Exclusion criteria
* Has received influenza vaccination within 6 months * Other vaccination planned within 8 weeks (including covid-19 booster doses) * Severe allergy to eggs or previous allergic reaction to influenza vaccine * Cardiac surgery or staged PCI planned within 8 weeks * Coronary stent involving the proximal RCA * Suspicion of febrile illness or acute, ongoing infection * Hypersensitivity to the active substances or ingredients of Vaxigrip or against any residues, such as eggs (ovalbumin or chicken proteins), neomycin, formaldehyde and octoxinol * Subjects with endogenic or iatrogenic immunosuppression that may result in reduced immunization response * Inability to provide informed consent * Previous randomization in the ELIMINATE trial * Any non-cardiovascular condition, e.g. malignancy, with a life expectancy of less than 1 year based on the investigator´s clinical judgement. * Contraindication to coronary CT angiography (e.g., inability to lie flat, contraindication to glyceryl trinitrate, previous contrast allergy or contrast-induced nephropathy, severe renal impairment \[eGFR \<30 mL/min/1.73 m2\]) * Atrial fibrillation * Uncontrolled chronic inflammatory disease * Unable to comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The right coronary artery | Between baseline and 8 weeks follow up. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The whole coronary tree | Between baseline and 8 weeks follow up. | Change from baseline in the average pericoronary adipose tissue density of the whole coronary tree (main epicardial arteries ≥2mm). |
| Ascending aorta | Between baseline and 8 weeks follow up. | Change from baseline in the perivascular adipose tissue density of the ascending aorta |
| Interleukin 1 beta (IL-1β) | Between baseline and 8 weeks follow up. | Difference in peripheral blood IL-1β concentrations |
| Tumor necrosis factor alpha (TNF-α) | Between baseline and 8 weeks follow up. | Difference in peripheral blood TNF-α concentrations |
| Interleukin-2 receptor (IL-2r) | Between baseline and 8 weeks follow up. | Difference in peripheral blood IL-2r concentrations |
| Interleukin Interleukin-6 (IL-6 ) | Between baseline and 8 weeks follow up. | Difference in peripheral blood IL-6 concentrations |
| Ferritin | Between baseline and 8 weeks follow up. | Difference in peripheral blood ferritin concentrations |
| Troponin-I | At 8 weeks follow up. | Differences in peripheral blood troponin-I concentrations between study groups |
| N-terminal pro-B-type natriuretic peptide | At 8 weeks follow up. | Differences in peripheral blood N-terminal pro-B-type natriuretic peptide concentrations between study groups |
Countries
Denmark, Sweden, United Kingdom
Contacts
CONTACTSara Cajander, MD
PRINCIPAL_INVESTIGATORSara Cajander, MD
Region Örebro län
STUDY_CHAIROle Frøbert, professor
Region Örebro län
Outcome results
None listed