Efficacy and Tolerance of Fludrocortisone Acetate in Neurogenic Orthostatic Hypotension: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of a 4-week treatment with fludrocortisone (FLU) at a stable dose on the decrease of systolic and diastolic blood pressure after 5 minutes of active orthostatism in patients with **neurogenic orthostatic hypotension** (NOH). This is clinically relevant as it aims to address the symptomatic blood pressure drop associated with NOH, which can lead to dizziness, fainting, and falls, thereby improving patient safety and quality of life.

Secondary objectives include:

• Evaluating the efficient dose of FLU to control NOH.
• Assessing the effect of FLU on systolic blood pressure in supine and stand-up positions.
• Evaluating the effect of FLU treatment on the prevalence and severity of symptoms related to NOH.
• Determining the full and partial responders rate during treatment with FLU.
• Assessing the effect of the treatment on nocturnal decubitus blood pressure.
• Evaluating the effect of the treatment on left ventricular mass and ejection fraction via cardiac ultrasound.
• Assessing the safety of FLU in the studied indication by monitoring adverse events.
• Evaluating the effect of the treatment on the quality of life.

The clinical trial involves participants diagnosed with **neurogenic orthostatic hypotension** (NOH), a condition characterized by a significant decrease in blood pressure upon standing. The study population includes both male and female subjects, aged 18 years and older, who are experiencing persistent and symptomatic NOH despite the use of non-medicinal measures and medicinal products. Participants are selected based on their diagnosis of a neurologic or metabolic disease known to be associated with autonomic nervous system dysfunction, such as Parkinson's disease, multisystem atrophy, Lewy body dementia, isolated progressive dysautonomia, diabetes, or renal failure. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The study population includes individuals who are considered vulnerable, and lifestyle factors such as diet and physical activity are not explicitly mentioned. Key inclusion criteria require participants to have a documented decrease in systolic and diastolic blood pressure within three minutes of standing, as well as symptomatic responses according to the Orthostatic Hypotension Questionnaire.

The clinical trial is designed to evaluate the efficacy and tolerance of **fludrocortisone acetate** in the treatment of **neurogenic orthostatic hypotension**. This study is a randomized, double-blind, controlled trial, conducted over a period of approximately six years, with an estimated end date of December 31, 2026. The trial involves a 4-week treatment phase where participants receive either the active drug, Flucortac 50 microgrammes, or a placebo, administered orally in tablet form. The primary objective is to assess the efficacy of fludrocortisone on the decrease of systolic and diastolic blood pressure after five minutes of active orthostatism. Secondary endpoints include the evaluation of symptoms related to neurogenic orthostatic hypotension through the Orthostatic Hypotension Questionnaire (OHQ) scale, quality of life assessment via the SF36 scale, and the collection of clinical adverse events, biological, and blood pressure anomalies.

Participants eligible for inclusion are adults over 18 years of age with persistent and symptomatic neurogenic orthostatic hypotension, despite the use of non-medicinal measures and medicinal products such as midodrine. The inclusion visit, or screening visit, will confirm eligibility based on these criteria. Following randomization, participants will attend regular follow-up visits to monitor blood pressure changes and assess any adverse events. The end-of-study visit will conclude the participant's involvement, with a comprehensive evaluation of the treatment's impact on their condition. The expected length of participant involvement is approximately four weeks, corresponding to the treatment duration. Conditions that may lead to early termination from the study include significant adverse reactions or non-compliance with the study protocol. The trial is categorized as a Phase IV clinical trial, indicating it is conducted after the drug has been approved for public use, to further evaluate its effects in a larger population. The study is not classified as low intervention, ensuring rigorous monitoring and data collection throughout the trial period.

The clinical trial involves the administration of **Fludrocortisone Acetate**, marketed under the name **FLUCORTAC 50 microgrammes, comprimé sécable**. This experimental medication is provided in tablet form and is intended for oral administration. The dosage regimen specifies a maximum daily dose of 200 micrograms, with a total maximum dose of 36,000 micrograms over the course of the treatment. The treatment period is set for a maximum of 6 weeks. The active substance, **Fludrocortisone Acetate**, is of chemical origin and is classified under the ATC code H02AA02. The primary objective of the trial is to evaluate the efficacy of this medication in reducing systolic and diastolic blood pressure in patients with neurogenic orthostatic hypotension after 5 minutes of active orthostatism.

In addition to the experimental treatment, a **placebo** is utilized in the study. The placebo is identified as **Cellulose microcristalline 50 microgrammes**. It does not contain any active pharmaceutical ingredient and serves as a control to assess the efficacy of the experimental medication. The placebo is not associated with any specific pharmaceutical form or route of administration in the trial documentation. The use of a placebo is critical in ensuring the reliability and validity of the trial results by providing a baseline for comparison against the effects observed with the active treatment.

The efficacy of fludrocortisone in the treatment of **neurogenic orthostatic hypotension** will be assessed through a clinical trial with a primary focus on the decrease of systolic and diastolic blood pressure after 5 minutes of active orthostatism. The primary endpoint involves measuring the efficacy on the systolic and diastolic blood pressure decrease when transitioning from a supine to a stand-up position. Secondary endpoints include the evaluation of symptoms related to neurogenic orthostatic hypotension using the Orthostatic Hypotension Questionnaire (OHQ) scale, assessment of quality of life through the SF36 scale, and the collection of clinical adverse events, as well as biological and blood pressure anomalies.

The trial will involve a 4-week treatment period with fludrocortisone at a stable dose. Efficacy parameters will be collected and analyzed at specified timepoints, although the exact schedule is not detailed. The use of validated scales such as the OHQ and SF36 will ensure the reliability of patient-reported outcomes. The trial is categorized as a Phase IV clinical trial, indicating it is conducted post-marketing to gather additional information on the drug's effectiveness and safety in a larger population.