Intranasal Corticosteroid Spray for Preventing Otitis Media With Effusion After Radiotherapy in Nasopharyngeal Carcinoma

Официальное название

Efficacy of Intranasal Corticosteroid Spray in Preventing Otitis Media With Effusion After Radiotherapy for Nasopharyngeal Carcinoma: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial

Обзор

This study focuses on a common side effect experienced by many patients after radiation therapy for nasopharyngeal cancer, which is a type of head and neck cancer. This side effect is called secretory otitis media (fluid buildup in the middle ear). It can cause a feeling of fullness in the ear and hearing loss. While procedures like ear tube placement can help, they can also lead to other problems like ear infections and drainage. Radiation treatment is thought to cause inflammation that disrupts the normal function of the tube connecting the ear to the throat (Eustachian tube), leading to this fluid buildup. A nasal spray containing a steroid medicine (triamcinolone acetonide) is already known to be safe and effective at reducing inflammation in the ear fluid of both children and adults. We believe that using this spray may also help prevent and improve this condition in nasopharyngeal cancer patients after radiation therapy. The main goal of this study is to explore whether this nasal spray can effectively prevent or reduce fluid buildup in the ear following radiation therapy. We hope this non-invasive treatment will provide a new option to improve the quality of life for these patients.

Подробное описание

Background and Rationale:

Nasopharyngeal carcinoma (NPC) is endemic in Southern China. While radiotherapy has significantly improved survival rates, radiation-induced complications severely impact quality of life. Otitis media with effusion (OME) is a highly prevalent complication, with an acute phase (during radiotherapy up to 3 months post-treatment) incidence of 30%-70%. Notably, 20%-40% of these cases progress to chronic OME, and 10%-30% require invasive procedures like tympanostomy tube insertion due to persistent symptoms and hearing loss (often \>30 dB).

The pathophysiology of radiation-related OME is distinct from generic OME. It involves mucosal injury in the Eustachian tube region (especially at radiation doses ≥60 Gy), leading to ciliary dysfunction, local immune dysregulation, and mechanical obstruction. Post-radiation changes also include mucosal structure alteration, local immunosuppression, and impaired mucociliary clearance, creating a persistent inflammatory environment conducive to effusion formation.

Current management, primarily adapted from conventional OME protocols (e.g., tympanostomy), offers short-term symptom relief but is associated with significant long-term complications, including chronic otorrhea (15%-20%) and persistent tympanic membrane perforation (5%-10%). This highlights the critical need for preventive and non-invasive strategies targeting the underlying inflammatory etiology.

Topical intranasal corticosteroids, such as triamcinolone acetonide, offer a mechanistically grounded prophylactic approach. They exert potent local anti-inflammatory and immunomodulatory effects by targeting and inhibiting the NF-κB pathway. This action can potentially mitigate mucosal inflammation, restore ciliary function, and rebalance local immunity in the nasopharynx and Eustachian tube orifice during and after radiotherapy, thereby preventing the initiation of the effusion process. Evidence supports their efficacy and safety in managing OME in other populations, with randomized controlled trials (e.g., by El-Anwar et al.) showing non-inferiority to systemic steroids with a significantly improved adverse effect profile (60%-70% reduction in systemic adverse events), making them suitable for long-term use in this patient population.

Study Objective and Design:

This study is a phase III, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy of prophylactic intranasal triamcinolone acetonide in reducing the incidence and severity of radiation-related OME in patients with NPC.

The intervention will be initiated concurrently with radiotherapy. Participants will be randomly assigned to receive either triamcinolone acetonide nasal spray or an identical placebo spray. The primary outcome is the incidence of clinically significant OME requiring intervention within a specified post-radiation period. Key secondary endpoints include objective measures of hearing function (pure-tone audiometry to assess hearing threshold shifts), tympanometric changes, the need for invasive procedures (tympanocentesis or tube placement), and patient-reported quality of life measures assessed using validated questionnaires.

This study aims to provide high-level evidence for a novel, preventive strategy targeting the inflammatory pathogenesis of radiation-induced OME, ultimately aiming to improve long-term otological outcomes and quality of life for NPC survivors.

Вмешательства

• Препарат Triamcinolone Acetonide
  Triamcinolone acetonide is a medium-potency synthetic corticosteroid. This intervention is administered via a commercially available, metered-dose nasal spray that delivers 55 μg of the active drug per spray. It exerts potent local anti-inflammatory and immunomodulatory effects in the nasal mucosa and Eustachian tube orifice. In this study, it is investigated for the prevention of radiotherapy-induced otitis media with effusion in patients with nasopharyngeal carcinoma.
• Препарат Placebo
  The placebo nasal spray is specifically formulated to be indistinguishable from the active triamcinolone acetonide nasal spray. It is identical in all physical properties including appearance, scent, taste, packaging, and administration procedure. It contains the same inactive excipients (e.g., preservatives, suspending agents) but does not contain any triamcinolone acetonide or other active pharmaceutical ingredient.

Первичные конечные точки

• Incidence of Otitis Media with Effusion (OME) within 12 months after radiotherapy [Срок оценки: From initiation of study intervention (radiotherapy start) until 12 months after completion of radiotherapy.]

Вторичные конечные точки (4)

• Time to onset of Otitis Media with Effusion (OME) [Срок оценки: From the start of radiotherapy until the first occurrence of OME, assessed up to 12 months after radiotherapy completion.]
• Change in pure-tone average hearing threshold [Срок оценки: Baseline (pre-radiotherapy), and at 3 month, 6 months, and 12 months after completion of radiotherapy.]
• Tympanometry results [Срок оценки: Baseline (pre-radiotherapy), and at 3 month, 6 months, and 12 months after completion of radiotherapy.]
• Change in disease-specific quality of life scores [Срок оценки: Baseline (pre-radiotherapy), and at 3 months, 6 months, and 12 months after completion of radiotherapy.]

Критерии участия

Критерии включения

• Pathologically confirmed nasopharyngeal carcinoma scheduled for curative intensity-modulated radiation therapy (IMRT), with or without concurrent chemotherapy.
• Age between 18 and 75 years.
• No previous history of head and neck radiotherapy.
• Intact tympanic membranes bilaterally at baseline, with no history of middle ear surgery (including tympanostomy tube placement).
• Willing to comply with all study procedures, including nasal spray use, audiological examinations, and follow-up visits.
• No use of systemic or topical corticosteroids, antihistamines, or decongestants within 14 days prior to randomization.
• All inclusion criteria must be met for participation

Критерии исключения

• Diagnosed with complete conductive hearing loss or ossicular chain fixation.
• Scheduled to undergo tympanostomy tube placement, tympanotomy, or other middle ear surgery prior to randomization.
• Unlikely to complete the 12-month follow-up (e.g., planned relocation, poor compliance).
• Presence of respiratory conditions requiring treatment with nasal corticosteroids.
• Known allergy or hypersensitivity to nasal corticosteroids (especially triamcinolone acetonide or its excipients).
• History of severe mental illness, cognitive impairment, or substance abuse that may affect compliance.
• Pregnant or lactating women, or women of childbearing potential unwilling to use effective contraception.
• Participation in other investigational drug clinical trials within the past 3 months.
• Deemed unsuitable for the trial by the investigator (e.g., severe septal deviation, chronic rhinosinusitis requiring systemic treatment, or poorly controlled diabetes).
• Any subject who meets any of the above exclusion criteria at baseline will be excluded from the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07189572 · UHCT250873

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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