Effect of infLuenza vaccInation After Myocardial INfArction on Cardiac inflammaTory responsE (ELIMINATE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Inflammatory Response; Acute Myocardial Infarction
• Intervention / Treatment: Biological: Influenza vaccine; Biological: 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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sara Cajander, MD; Phone Number: +46196021000 +46196021042; Email: sara.cajander@oru.se

Study Locations

• Sweden
  • Örebro, Sweden, 70185
    • Recruiting
    • Örebro University Hospital
    • Contact: Sara Cajander; Phone Number: +46702261026; Email: sara.cajander@oru.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vaccination arm; Influenza vaccine (Vaxigrip Tetra Sanofi Pasteur Europe).	Biological: Influenza vaccine; VaxigripTetra Suspension for injection, 0,5ml prefilled syringe ATC code: J07BB02
Placebo Comparator: Placebo arm; Sodium Chloride (Placebo) Solution for infusion, 9mg/ml ATC code: B05BB01	Biological: Placebo; Sodium Chloride Solution for infusion, 9mg/ml ATC code: B05BB01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Secondary Outcome Measures

Outcome Measure	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	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.

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: University of Cambridge; Örebro University, Sweden; The Swedish Heart and Lung Association
• Investigators: Principal Investigator: Sara Cajander, MD, Region Örebro län; Study Chair: Ole Frøbert, professor, Region Örebro län

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Influenza vaccine; Percutaneous coronary intervention; Coronary computed tomography angiography; Non ST-segment elevation myocardial infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Vascular Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Myocardial Infarction; Infarction; Cardiovascular Diseases; Influenza, Human
• Other Study ID Numbers: ELIMINATE-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No