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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 168
- 主要终点
- Incidence of Otitis Media with Effusion (OME) within 12 months after radiotherapy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Triamcinolone Acetonide (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Otitis Media with Effusion (OME) within 12 months after radiotherapy
时间窗: From initiation of study intervention (radiotherapy start) until 12 months after completion of radiotherapy.
The occurrence of OME is determined by a combination of: 1) Presence of relevant symptoms (e.g., ear fullness, hearing loss); AND 2) Confirmatory physical examination findings on otoscopy (e.g., tympanic membrane retraction, air-fluid levels, bubbles); AND 3) Objective evidence from tympanometry (Type B or Type C curve, indicating middle ear effusion or significant negative pressure). A case of OME is only confirmed if all three criteria are met. The incidence is calculated as the proportion of participants in each group who develop confirmed OME at any point during the 12-month follow-up period after the completion of radiotherapy.
次要结局
- Time to onset of Otitis Media with Effusion (OME)(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(Baseline (pre-radiotherapy), and at 3 month, 6 months, and 12 months after completion of radiotherapy.)
- Tympanometry results(Baseline (pre-radiotherapy), and at 3 month, 6 months, and 12 months after completion of radiotherapy.)
- Change in disease-specific quality of life scores(Baseline (pre-radiotherapy), and at 3 months, 6 months, and 12 months after completion of radiotherapy.)