Evaluation of Influenza Vaccine on Systemic Inflammatory Markers in Stable Coronary Artery Disease Patients: A Randomized Delayed-Start Pilot Study

The primary objective of this study is to evaluate the impact of **influenza vaccination** at one month on the systemic inflammatory response, specifically measured by high-sensitivity C-reactive protein (hsCRP), in patients with stable **coronary artery disease**. This is clinically relevant as systemic inflammation is a known contributor to cardiovascular events, and understanding the effects of influenza vaccination on inflammation could inform preventive strategies in this patient population.

Secondary objectives include: - Evaluating the impact of influenza vaccination at one month on other markers of inflammation. - Assessing the impact on markers of arterial vulnerability. - Characterizing the immunoinflammatory response within circulating immune cells at one month post-vaccination. - Evaluating correlations between vaccine-induced strain-specific antibody responses and levels of systemic inflammation at one month post-vaccination.

The clinical trial involves **patients with stable coronary artery disease**. The study population includes both male and female subjects aged 60 years and older. Participants are required to have documented stable coronary artery disease and must be able to comply with protocol requirements, such as attending follow-up visits and communicating with study staff. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must be affiliated with a French social security system and have provided free, written, and informed consent. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the impact of **influenza vaccination** on systemic inflammatory markers in patients with stable coronary artery disease. This is a randomized, delayed-start pilot trial, categorized as a low-intervention study, and is conducted in Phase 4. The trial will involve a controlled, double-blind methodology to ensure unbiased results. The trial is scheduled to commence on October 21, 2024, with an estimated end date of January 16, 2025, and recruitment is expected to conclude by January 20, 2025.

Participants will be involved in the study for approximately one month. The study will begin with an inclusion visit, where eligibility criteria will be confirmed, and baseline measurements, including plasma high-sensitivity C-reactive protein (hsCRP) levels, will be taken. Participants will be randomly assigned to either the intervention group, receiving immediate vaccination, or the control group, receiving vaccination after one month. The primary endpoint is the change in hsCRP levels from baseline to the end of the study. Secondary endpoints include the measurement of other inflammatory markers, arterial vulnerability markers, characterization of circulating immune cells, and antibody titers.

Study visits will include the initial screening, a follow-up visit at one month, and an end-of-study visit. The follow-up visit will assess the primary and secondary endpoints, including the measurement of hsCRP and other inflammatory markers. The end-of-study visit will finalize data collection and ensure participant safety. Participants may be withdrawn from the study if they fail to comply with protocol requirements, experience adverse reactions, or withdraw consent. The trial aims to provide insights into the potential immunomodulatory effects of influenza vaccination in this patient population, potentially informing future multicentric randomized trials.

The clinical trial involves the administration of **VAXIGRIPTETRA**, a quadrivalent influenza vaccine, which is provided as a **suspension for injection** in a pre-filled syringe. The vaccine is designed to protect against four strains of the influenza virus: **B/Phuket/3073/2013-like virus** (wild type), **Influenza virus B/Michigan/01/2021**, **Influenza A/Victoria/4897/2022 IVR-238 (H1N1), inactivated**, and **Influenza virus A/California/122/2022 SAN-022 (H3N2) strain (split, inactivated)**. The vaccine is administered via **intramuscular injection**. The dosage for each participant is 0.5 ml, with a maximum total dose of 0.5 ml, administered as a single dose. The treatment period is limited to one day, ensuring a straightforward administration schedule.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the VAXIGRIPTETRA vaccine. Participant compliance is monitored through standard clinical trial procedures, ensuring adherence to the dosing schedule and accurate recording of any adverse events or reactions. The trial aims to evaluate the impact of influenza vaccination on systemic inflammatory markers in patients with stable coronary artery disease.

The efficacy of the influenza vaccine in patients with stable coronary artery disease will be assessed by measuring the primary endpoint, which is the plasma concentration of high-sensitivity C-reactive protein (**hsCRP**). This biomarker will be evaluated at two timepoints: at inclusion (baseline value before vaccination) and at the end of the study (1 month post-vaccination). The change in **hsCRP** levels will be compared between the intervention group, which receives the vaccination immediately after inclusion, and the control group, which receives the vaccination at 1 month.

Secondary endpoints include the plasma concentrations of additional inflammatory markers associated with cardiovascular disease risk, such as interleukin (IL)-6, IL-1b, tumor necrosis factor-α, NT-pro-BNP, and fibrinogen. Additionally, plasma concentrations of arterial vulnerability markers, including Apolipoprotein B, lipoprotein(a), and LDL, will be measured. The characterization of circulating immune cells will be conducted by analyzing the expression levels of genes involved in the T cell response using RT-qPCR and determining the percentage of B lymphocytes, T lymphocytes, and monocytes among PBMCs through flow cytometry. Furthermore, antibody titers will be assessed at 1 month using the hemagglutination inhibition titer for each strain of the vaccine.