Evaluation of Hyperbaric Oxygen Therapy Combined with Standard Care in Acute Idiopathic Sudden Sensorineural Hearing Loss: A Multicenter Randomized Controlled Trial

The primary objective of this study is to evaluate whether the addition of **hyperbaric oxygen therapy (HBOT)** to standard care results in improved hearing outcomes three months post-treatment compared to standard care alone in patients with **idiopathic sudden sensorineural hearing loss (ISSNHL)**. This is clinically relevant as ISSNHL is a condition that can lead to significant hearing impairment, and optimizing treatment strategies is crucial for enhancing patient outcomes.

Secondary objectives include: - Assessing the association of age and the severity of hearing loss with hearing improvement after both treatments. - Evaluating the impact of hearing levels and improvement on communication problems and quality of life. - Assessing the safety of HBOT for ISSNHL. - Investigating the impact of the frequency distribution of hearing loss on the course, outcome, and effect of both treatments. - Evaluating the impact of cardiovascular risk factors on treatment outcomes. - Assessing the prevalence and course of vestibular dysfunction and its correlation with hearing loss characteristics and outcomes. - Examining the course of hearing improvement during the first three months.

The clinical trial focuses on participants diagnosed with **idiopathic sudden sensorineural hearing loss (ISSNHL)**. The study population includes both male and female subjects, aged between 18 to 80 years. Participants are required to have experienced the onset of acute hearing loss no longer than 7 days prior to enrollment, with the ability to commence hyperbaric oxygen therapy (HBOT) within this timeframe. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status is not specified, but they must have a pure tone audiometry showing sensorineural hearing loss with at least a 30 dB loss in three consecutive frequencies, and a hearing threshold of 50 dB or more in pure tone audiometry (PTA) based on 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that idiopathic sensorineural hearing loss is the most probable diagnosis according to clinical judgment.

The clinical trial is designed to evaluate the efficacy of **hyperbaric oxygen therapy (HBOT)** in addition to standard care for patients with **idiopathic sudden sensorineural hearing loss (ISSNHL)**. This is a multicenter, randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is set to commence on January 1, 2025, and is expected to conclude by December 31, 2026. Participants will be involved in the study for a maximum of 16 weeks, with the primary endpoint being the mean absolute pure tone average (PTA) at week 14.

Study visits are structured to include an initial screening visit, where eligibility is confirmed based on criteria such as age (18 to 80 years), recent onset of hearing loss (within 7 days), and specific audiometric thresholds. Following randomization, participants will undergo regular follow-up visits to monitor progress and assess hearing recovery. The end-of-study visit will occur at week 14, where final assessments will be conducted, including PTA and word recognition scores. Secondary endpoints will evaluate changes in PTA, hearing recovery categories, and patient-reported outcomes.

Participants may be withdrawn from the study if they experience adverse events that compromise safety or if they require additional treatments not permitted by the protocol. The trial will utilize **oxygen** and **nitrous oxide** as inhalation gases, with a maximum daily dose of 95 minutes and a total dose not exceeding 1520 minutes over the treatment period. The study aims to provide robust data on the potential benefits of HBOT in enhancing hearing recovery in ISSNHL patients.

The clinical trial involves the administration of a **gas for inhalation** composed of **nitrous oxide** and **oxygen**. The pharmaceutical form of the product is designated as PHF763. The active substances, **nitrous oxide** and **oxygen**, are of chemical origin. The gas is administered via the **inhalation route**. The maximum daily dose is 95 minutes, with a total maximum dose of 1520 minutes over a treatment period not exceeding 16 days. The product is not a pediatric formulation and is not classified as an orphan drug. The administration of the gas is monitored to ensure compliance with the dosing schedule.

In addition to the experimental treatment, participants receive standard-of-care therapy for acute idiopathic sudden sensorineural hearing loss. This standard care serves as a comparator treatment to evaluate the efficacy of the experimental gas inhalation therapy. The trial aims to determine if the addition of hyperbaric oxygen treatment (HBOT) to standard care results in improved hearing outcomes three months post-treatment compared to standard care alone. Participant compliance with both the experimental and standard treatments is closely monitored throughout the trial duration.

Efficacy in this clinical trial will be assessed by evaluating the impact of hyperbaric oxygen treatment (HBOT) added to standard care for patients with acute idiopathic sudden sensorineural hearing loss (ISSNHL). The primary endpoint for efficacy evaluation is the mean absolute pure tone average (PTA) at week 14. PTA is defined as the mean hearing threshold in decibels (dB) across four frequencies: 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz.

Secondary endpoints include the mean change in PTA from baseline to week 14, the proportion of patients with an improvement of at least 10 dB in PTA from baseline to week 14, and the mean word recognition score (WRS) in percentage points at week 14 and its change from baseline. Additional secondary endpoints involve categorizing hearing recovery according to Siegel's criteria at week 14 and assessing hearing-loss severity according to the AAO-HNS criteria at baseline and week 14. The trial will also measure the proportion of patients receiving additional treatment post-study, the total score of patient-reported communication problems using the APHAB questionnaire at day 1 and week 14, and RAND-12 scores at the same time points. Furthermore, the trial will document the number of adverse events (AEs) and serious adverse events (SAEs) in both groups, as well as the occurrence of known side effects of HBOT.