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

NCT ID: NCT07189572

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2027-10-31

Brief Summary

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.

Detailed Description

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.

Conditions

Otitis Media; Otitis Media With Effusion After Nasopharyngeal Carcinoma; Radiotherapy Side Effects; Radiotherapy Side Effect; Otitis Media With Effusion (OME)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Triamcinolone Acetonide Nasal Spray

Participants will receive triamcinolone acetonide nasal spray (55 μg/spray) in addition to concurrent cisplatin-based chemoradiation. The intervention is initiated on day 1 of radiotherapy. The dosing regimen is 2 sprays per nostril (total daily dose of 220 μg) administered each morning for 12 weeks, covering the entire radiotherapy course and the acute inflammatory phase. All patients will also perform daily nasal irrigation with normal saline, timed at least 30 minutes apart from the drug administration.

Group Type: EXPERIMENTAL

Triamcinolone Acetonide

Intervention Type: DRUG

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.

Placebo Nasal Spray

Participants will receive a matching placebo nasal spray, which is identical in appearance and usage to the active drug, in addition to concurrent cisplatin-based chemoradiation. The intervention is initiated on day 1 of radiotherapy. The dosing regimen is 2 sprays per nostril administered each morning for 12 weeks. All patients will also perform daily nasal irrigation with normal saline, timed at least 30 minutes apart from the placebo administration.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

UHCT250873

Identifier Type: -

Identifier Source: org_study_id