Evaluation of Beta-Adrenergic Blockers on Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement for Aortic Stenosis

The primary objective of this study is to evaluate the impact of **beta blocker** administration on patients undergoing transcatheter aortic valve replacement (TAVR). This investigation is clinically relevant as it aims to determine the potential benefits or risks associated with beta blocker use in the context of TAVR, a procedure performed to treat **aortic stenosis**. Understanding the effects of beta blockers in this setting could inform clinical decisions and optimize patient outcomes.

The clinical trial involves a total of **300 participants** diagnosed with **aortic stenosis**. The study population includes both male and female adults aged 18 years and older, who are eligible and scheduled for elective transcatheter aortic valve replacement (TAVR). Participants are required to have a prior indication for beta-blocker therapy with a treatment duration of at least one month before inclusion. The trial population was selected based on their ability to provide informed consent and their clinical eligibility for TAVR. The study considers individuals with severe symptomatic aortic stenosis, and the participants are expected to maintain their current lifestyle, including any relevant dietary or physical activity habits, throughout the trial. The trial does not exclude vulnerable populations, ensuring a comprehensive assessment of the intervention's impact across diverse demographic groups.

The clinical trial is designed to evaluate the impact of **beta-blocker** administration on patients undergoing transcatheter aortic valve replacement (TAVR) for severe symptomatic **aortic stenosis**. This is a Phase IV, randomized, double-blind, controlled trial, categorized as a low-intervention study. The trial will span approximately three years, with an estimated recruitment start date of June 30, 2025, and an estimated end date of May 31, 2028. Participants will be randomly assigned to receive either a beta-blocker or a placebo, with the intervention administered orally. The maximum treatment period for each participant is six months.

The study will include several key visits: an initial screening visit, follow-up visits, and an end-of-study visit. During the **screening visit**, eligibility will be confirmed based on inclusion criteria, such as being an adult patient with severe symptomatic aortic stenosis eligible for elective TAVR and having an indication for beta-blocker therapy with a prior treatment duration of at least one month. Informed consent must be obtained before any study intervention. Follow-up visits will occur at 30 days and one year post-intervention to assess primary and secondary endpoints, including all-cause mortality, rehospitalization due to heart failure, stroke, and severe arrhythmia. The **end-of-study visit** will conclude the participant's involvement in the trial.

Participant involvement is expected to last up to one year, with conditions for early termination including withdrawal of consent or any adverse events that may pose a risk to the participant's health. The trial aims to provide valuable insights into the efficacy and safety of beta-blockers in the context of TAVR, with minimal additional risk or burden to the subjects, as the investigational medicinal products are authorized and routinely prescribed as part of standard care.

The clinical trial involves the administration of several **beta-blocking agents** to evaluate their impact on patients undergoing transcatheter aortic valve replacement (TAVR). The first experimental medication is a selective beta-blocking agent, classified under the ATC code C07AB. This medication is administered orally in a pharmaceutical form identified as PHF00082MIG. The maximum daily dose is 400 mg, with a total maximum dose of 2400 mg over a treatment period of up to six months.

The second experimental medication is a combination of selective beta-blocking agents and thiazides, classified under the ATC code C07BB. This medication is also administered orally in the same pharmaceutical form, PHF00082MIG. The maximum daily dose for this treatment is 200 mg, with a total maximum dose of 1200 mg over a six-month period.

The third experimental medication is a combination of alpha and beta-blocking agents with thiazides, classified under the ATC code C07BG. This medication is administered orally in the pharmaceutical form PHF00082MIG. The maximum daily dose is 50 mg, with a total maximum dose of 300 mg over a six-month treatment period.

The fourth experimental medication is a combination of alpha and beta-blocking agents, classified under the ATC code C07AG. This medication is administered orally in a different pharmaceutical form, PHF00009MIG. The maximum daily dose is 50 mg, with a total maximum dose of 300 mg over a six-month period.

The fifth experimental medication is a non-selective beta-blocking agent, classified under the ATC code C07AA. This medication is administered orally in the pharmaceutical form PHF00082MIG. The maximum daily dose is 640 mg, with a total maximum dose of 3840 mg over a six-month treatment period.

All medications are administered orally, and the treatment period for each is up to six months. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data provided.

Efficacy in this clinical trial will be assessed using a composite primary endpoint, which includes all-cause mortality, rehospitalization due to heart failure, stroke, and severe arrhythmia (such as new onset atrial fibrillation/flutter, ventricular tachycardia/ventricular fibrillation, and new high-grade AV-Block) at 30 days. Secondary endpoints will further evaluate efficacy by measuring pacemaker rate, stroke rate, all-cause mortality, cardiovascular mortality, and rehospitalization due to heart failure at both 30 days and 1 year. Additionally, the occurrence of severe arrhythmias requiring treatment, including new onset atrial fibrillation/flutter, ventricular tachycardia/ventricular fibrillation, new AV Block, new left or right bundle branch block, intraventricular conduction delay, new severe bradycardia, tachycardia, and sick sinus syndrome, will be assessed at these timepoints.

The trial will involve the administration of **beta-blockers** to patients undergoing transcatheter aortic valve replacement (TAVR). The efficacy parameters will be collected and analyzed at specified intervals, namely at 30 days and 1 year post-treatment. The study is designed as a low intervention trial, utilizing authorized beta-blockers that are routinely prescribed as part of standard care, ensuring minimal additional risk or burden to the subjects. The trial is categorized as a Phase IV clinical trial, with the investigational medicinal products used in accordance with their marketing authorizations.