Effect of infLuenza vaccInation After Myocardial INfArction on Cardiac inflammaTory responsE

Cardiovascular Diseases Clinical Trial

— ELIMINATE  

Official title:

Effect of infLuenza vaccInation After Myocardial INfArction on Cardiac inflammaTory responsE - a Randomized, Double-blind, Placebo-controlled, Trial (ELIMINATE Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06336317
• Other study ID #: ELIMINATE-2024
• Status: Recruiting
• Phase: Phase 4
• Start date: April 24, 2024
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Region Örebro County
• Contact: Sara Cajander, MD
• Phone: +46196021042
• Email: sara.cajander[@]oru.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Cardiovascular Diseases
• Infarction
• Inflammatory Response
• Influenza, Human
• Myocardial Infarction

Intervention

Biological:
• Influenza vaccine
VaxigripTetra Suspension for injection, 0,5ml prefilled syringe ATC code: J07BB02
• Placebo
Sodium Chloride Solution for infusion, 9mg/ml ATC code: B05BB01

Locations

Country	Name	City	State
Sweden	Örebro University Hospital	Örebro

Sponsors (4)

Lead Sponsor	Collaborator
Region Örebro County	Örebro University, Sweden, The Swedish Heart and Lung Association, University of Cambridge

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	8 weeks follow up
Other	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
Primary	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.
Secondary	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.
Secondary	Ascending aorta	Change from baseline in the perivascular adipose tissue density of the ascending aorta	Between baseline and 8 weeks follow up.
Secondary	Interleukin 1 beta (IL-1ß)	Difference in peripheral blood IL-1ß concentrations	Between baseline and 8 weeks follow up.
Secondary	Tumor necrosis factor alpha (TNF-a)	Difference in peripheral blood TNF-a concentrations	Between baseline and 8 weeks follow up.
Secondary	Interleukin-2 receptor (IL-2r)	Difference in peripheral blood IL-2r concentrations	Between baseline and 8 weeks follow up.
Secondary	Interleukin Interleukin-6 (IL-6 )	Difference in peripheral blood IL-6 concentrations	Between baseline and 8 weeks follow up.
Secondary	Ferritin	Difference in peripheral blood ferritin concentrations	Between baseline and 8 weeks follow up.
Secondary	Troponin-I	Differences in peripheral blood troponin-I concentrations between study groups	At 8 weeks follow up.
Secondary	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.