Brief Summary - OMENUTS Trial Otitis media with effusion (OME) is a condition in which fluid accumulates in the middle ear, causing conductive hearing loss, ear fullness, tinnitus, and Eustachian tube dysfunction. Although OME is well-recognized in children, it also affects adults, in whom it is frequently under-diagnosed and inadequately treated. No established, well-tolerated pharmacological therapy currently exists for adult OME, and current medical management options - including antihistamines, corticosteroids, and mucolytics - have shown inconsistent efficacy in clinical trials.

Omega-3 polyunsaturated fatty acids and associated nutraceutical compounds have well-documented anti-inflammatory and immunomodulatory properties that are mechanistically relevant to the pathophysiology of OME, which is driven by chronic low-grade mucosal inflammation, Eustachian tube dysfunction, and impaired mucociliary clearance. A nutraceutical combination containing omega-3 fatty acids, Spirulina, magnesium, and vitamin B6 has previously demonstrated efficacy in reducing inflammatory biomarkers and improving clinical outcomes in allergic rhinitis - a condition sharing key pathophysiological features with OME.

The OMENUTS trial is a multicenter, double-blind, randomized placebo-controlled trial designed to evaluate the efficacy of this nutraceutical combination as adjunctive therapy in adults with confirmed OME. The trial is conducted across three tertiary referral centres in Italy: Isola Tiberina - Gemelli Isola Hospital (Rome), the University of Catanzaro (Catanzaro), and Tortorella Clinic (Salerno).

A total of 501 adult participants aged 18 to 70 years with a confirmed diagnosis of OME - established by otoscopic examination and tympanometry (type B curve) of at least 4 weeks' duration - are randomized in a 1:1:1 ratio to one of three groups. All participants receive a shared background therapy of intranasal mometasone furoate spray and oral deflazacort for three weeks. In addition to the background therapy, participants in Group 1 (intervention group) receive the nutraceutical combination (omega-3 fatty acids, Spirulina, magnesium, and vitamin B6; one tablet daily) for three weeks; participants in Group 2 (active control group) receive oral bilastine 20 mg daily for three weeks; and participants in Group 3 (placebo group) receive an identical placebo tablet daily for three weeks.

The co-primary outcomes are tympanometric resolution - defined as normalization of the tympanometric curve from type B to type A - and audiometric improvement - defined as a reduction in pure-tone average of more than 15 dB HL - both assessed at the end of treatment (week 3, T1). Secondary outcomes include changes in patient-reported symptom severity (VAS), Eustachian tube dysfunction symptoms (ETDQ-7), psychosocial impact of hearing impairment (HHIA), and Eustachian tube patency assessed by the Valsalva maneuver. A 60-day post-treatment follow-up visit (T2) is included to evaluate recurrence rates across groups.

Randomization is computer-generated via REDCap, stratified by site, and implemented with permuted blocks of variable size. The trial is conducted under a double-blind design, with all investigational products identical in appearance, odour, and taste. Safety outcomes, including the incidence and nature of adverse events classified according to MedDRA criteria, are monitored continuously throughout the study.

The primary analysis is conducted on a modified intention-to-treat basis, including all participants who received at least one dose of the assigned treatment and completed at least one post-baseline assessment. The trial is conducted in accordance with the Declaration of Helsinki, CONSORT guidelines, and was approved by the Institutional Review Board of the Region of Calabria, Italy (approval code: 177/2026).