Evaluation of Semaglutide in Patients with Obesity and Resistant Hypertension: A Randomized, Parallel-Group, Multicenter Clinical Trial

The primary objective of this clinical trial is to assess the feasibility of conducting a study to determine whether targeting **obesity** with **semaglutide** in patients with resistant **hypertension** improves blood pressure control compared to a placebo. This objective is clinically relevant as it addresses the potential for semaglutide, a medication primarily used for weight management, to have a beneficial impact on blood pressure control in individuals with resistant hypertension, a condition that poses significant cardiovascular risks and is often challenging to manage with standard treatments.

The clinical trial focuses on individuals diagnosed with **cardiovascular disorders**, specifically hypertension and obesity. The study population includes both male and female participants, with an age range that encompasses adults and older adults. The trial targets individuals with a **body mass index (BMI)** of 30 kg/m² or higher, indicating obesity, and those with resistant hypertension, characterized by a mean home systolic blood pressure of 130 mmHg or higher, despite being prescribed three or more antihypertensive medications, including a diuretic. Participants are required to provide written informed consent and be available for trial activities. The sponsor has not provided information regarding the total number of participants. The trial population selection considers the inclusion of a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed in the available data.

The clinical trial is designed to evaluate the feasibility of using **semaglutide** to improve blood pressure control in patients with obesity and resistant hypertension. This is a randomized, double-blind, placebo-controlled, parallel-group trial. Participants will be randomly assigned to receive either semaglutide or a placebo, both administered via subcutaneous injection using pre-filled pens. The trial is expected to last for 36 weeks, with participant involvement spanning the same duration.

The study will commence with an inclusion visit, where potential participants will undergo screening to ensure they meet the principal inclusion criteria, such as having a body mass index (BMI) of 30 kg/m² or higher and resistant hypertension. Following successful screening and consent, participants will be randomized into the treatment or placebo group. The trial will include several follow-up visits to monitor blood pressure, assess the tolerability of the intervention, and record any adverse events. These visits will also evaluate the primary endpoints, including variability in systolic blood pressure and the feasibility of trial conduct. Secondary endpoints will assess changes in health-related quality of life and medication adherence.

The end-of-study visit will occur at the conclusion of the 36-week period, where final assessments will be conducted to gather data on the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience severe adverse events, fail to adhere to the study protocol, or withdraw consent. The trial aims to provide insights into the potential benefits of semaglutide for managing blood pressure in this patient population, with a focus on safety and intervention acceptability.

The clinical trial involves the administration of several formulations of **semaglutide**, a protein-based active substance, delivered as a solution for injection in pre-filled pens. The experimental medications include Wegovy and Ozempic, both manufactured by Novo Nordisk A/S. Wegovy is available in multiple dosages: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg, while Ozempic is available in 0.25 mg, 0.5 mg, and 1 mg dosages. Each formulation is designed for subcutaneous administration, with a maximum daily dose ranging from 0.25 mg to 2.4 mg, depending on the specific product. The maximum treatment period for each formulation is 36 weeks. The pharmaceutical form for all semaglutide products is a solution for injection in a pre-filled pen, ensuring ease of use and accurate dosing.

In addition to the experimental medications, a placebo is utilized in this trial. The placebo consists of an injection with an empty medical syringe with a needle attached. To maintain sterility and safety, a new sterile needle is used for each administration. During administration, a research nurse holds an accompanying training pen, which is 'clicked' to replicate the sound of a pre-filled pen administration. The medical syringe used is a BD Luer-Lok™ Syringe, and the needles attached are CE-Marked. The training pen is a commercially authorized CE-Marked pen. This placebo is designed to mimic the administration process of the active treatments without delivering any active substance.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on blood pressure measurement, specifically the variability in the mean difference in systolic blood pressure (SBP) after 36 weeks, and the correlation between home, ambulatory, and clinic SBP. Additionally, the trial will evaluate recruitment feasibility and reliability, intervention acceptability, and safety, including the incidence and severity of serious adverse events and routine follow-up for drug-related adverse events.

Secondary endpoints will include clinical measures such as the mean difference in home systolic and diastolic BP, changes in anti-hypertensive medications, body weight, and glycated hemoglobin (HbA1c) levels. Patient-reported outcomes will be assessed using validated questionnaires, including the EQ-5D-3L for health-related quality of life, the Beliefs about Medicines questionnaire, the Hill-Bone questionnaire for medication adherence, and the Best Health Program questionnaire for health lifestyle behaviors. Exploratory endpoints will examine composite BP changes and novel measures of BP control, such as SBP Load and Time in Target Range.

The efficacy parameters will be measured and collected at baseline and at the end of the 36-week treatment period. The trial will utilize validated scales and questionnaires to ensure the reliability and accuracy of the data collected. The analysis will focus on comparing the effects of **semaglutide** with placebo, both in addition to healthy lifestyle advice, to determine the impact on blood pressure control and other health outcomes in patients with obesity and resistant hypertension.