Evaluation of Intramyocardial Conduction Disorders Post-Percutaneous Aortic Valve Using 18F-Fludeoxyglucose PET-CT in Aortic Stenosis Patients

The primary objective of this study is to evaluate the **association** between the occurrence of conduction disorders following percutaneous aortic valve implantation and the degree of inflammation in intramyocardial conduction pathways. This is assessed using 18F-FDG PET-CT in an exploratory cohort. Understanding this association is clinically relevant as it may provide insights into the pathophysiology of conduction disorders post-procedure, potentially guiding future therapeutic strategies for patients with **aortic stenosis**.

Secondary objectives include:

• Studying the association between the degree of intramyocardial conduction pathway inflammation, as assessed by 18F-FDG PET-CT, and the need for pacemaker implantation after percutaneous aortic valve implantation.
• Identifying predictive factors for pacemaker dependence at 1 and 6 months post-implantation.

The clinical trial involves participants diagnosed with **aortic stenosis**, focusing on individuals over the age of 18. Both male and female subjects are included, with no specific vulnerable populations targeted. The study population is characterized by patients who have a tight aortic stenosis, as defined by specific echocardiographic criteria, and who are symptomatic or have a reduced left ventricular ejection fraction. Participants must have vascular anatomy suitable for percutaneous femoral valve implantation and be affiliated with a health insurance scheme. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Lifestyle factors such as diet, physical activity, or habits are not detailed in the available data. Key inclusion criteria include the provision of informed consent and the presence of symptoms or specific echocardiographic findings. The selection process ensures that participants meet these clinical and procedural requirements.

The clinical trial is designed to evaluate the association between conduction disorders following percutaneous aortic valve implantation and the degree of inflammation in intramyocardial conduction pathways, as assessed by **18F-FDG PET-CT**. This study is a phase 4, randomized, double-blind, controlled trial focusing on patients with **aortic stenosis**. The trial is expected to run from January 2022 to January 2026, with participant involvement lasting up to six months post-procedure. The primary endpoint is the intra-hospital occurrence of conductive disorders, including complete atrioventricular block (AVB), high-grade AVB, left bundle branch block (LBB), right bundle branch block (RBB), and AVB1, assessed via electrocardiograms during initial hospitalization. Secondary endpoints include post-TAVI pacemaker implantation and pacemaker dependence at one and six months, as well as the occurrence of conductive disorders within six months post-discharge.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, severity of aortic stenosis, and symptomatic status. Following the screening, eligible participants will receive the investigational product, **FLUDESOXYGLUCOSE (18F)-CURIUM 185 MBq/mL**, administered via intravenous injection. Follow-up visits will be scheduled to monitor the participants' health status and assess the primary and secondary endpoints. The end-of-study visit will conclude the trial for each participant, ensuring all data is collected and any adverse events are addressed.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial's methodology ensures rigorous data collection and analysis, contributing valuable insights into the relationship between inflammation and conduction disorders in patients with aortic stenosis.

The clinical trial involves the administration of **Fludeoxyglucose (18F)**, marketed as **FLUDESOXYGLUCOSE (18F)-CURIUM 185 MBq/mL**, which is a **solution for injection**. This experimental medication is utilized to evaluate the degree of inflammation in intramyocardial conduction pathways post percutaneous aortic valve intervention. The pharmaceutical form of the medication is a **solution injectable**, and it is administered via **intravenous injection**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 3 MBq/kg and a maximum total dose of 3 MBq/kg. The treatment period is limited to a single day. The active substance, **Fludeoxyglucose (18F)**, is of chemical origin and is produced by Curium International. The medication is not a pediatric formulation and is not classified as an orphan drug.

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 experimental medication to assess its impact on the specified clinical endpoints. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to explore the association between conduction disorders and inflammation using **18F-FDG PET-CT** imaging techniques.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the intra-hospital "occurrence of a conductive disorder," which is a composite criterion including complete atrioventricular block (AVB), high-grade AVB, left bundle branch block (LBB), right bundle branch block (RBB), and first-degree AVB. These will be evaluated using electrocardiograms (ECG) conducted post percutaneous valve implantation during the initial hospitalization period.

Secondary endpoints include the need for post-transcatheter aortic valve implantation (TAVI) pacemaker implantation, pacemaker dependence at 1 month and 6 months post-TAVI, and the "occurrence of a conductive disorder" within 6 months following discharge from TAVI hospitalization. These assessments will provide comprehensive data on the efficacy of the intervention in managing conduction disorders associated with percutaneous aortic valve procedures.