Doxepin Solution for Alleviation of Stubborn Breakthrough Pain Induced by Swallowing in Patients Receiving Radiotherapy for Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The goal of this clinical trial is to explore the effectiveness and adverse reactions of doxepin solution spray for alleviation of stubborn breakthrough pain induced by swallowing in patients receiving radiotherapy for nasopharyngeal carcinoma.

Detailed Description
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Patients with nasopharyngeal carcinoma receiving radical radiotherapy or chemoradiotherapy who developed oral mucositis and had a swallowing-induced pain score ≥ 4 were recruited and randomly assigned 1:1 to the experimental group and the control group. Patients in the experimental group received a doxepin solution spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a placebo spray was administered to the posterior pharyngeal wall 10 minutes before eating. Patients in the control group received a placebo spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a doxepin solution spray was administered to the posterior pharyngeal wall 10 minutes before eating. The swallowing-induced pain and incidence of adverse events were assessed at 10 minutes, 20 minutes, 30 minutes, and 1 hour after medication using a patient-reported questionnaire, and safety evaluation was conducted 1 day after treatment.

Official Title
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Doxepin Solution for Alleviation of Stubborn Breakthrough Pain Induced by Swallowing in Patient Receiving Radiotherapy for Nasopharyngeal Carcinoma: A Multicenter, Randomized, Controlled, Double-Blind Clinical Trial

Conditions
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Swallowing-induced Pain

Intervention / Treatment
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* Drug: doxepin solution
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed written consent. Age ≥ 18 years. Histologically confirmed as nasopharyngeal carcinoma, and currently undergoing radical radiotherapy or chemoradiotherapy. Physical examination demonstrating the presence of radiation-induced mucositis in the oral cavity and/or oropharynx. At least 4 (out of 10) patient-reported swallowing-induced pain as measured by the numeric rating scale of pain. Being able to complete the questionnaires independently or with assistance. ECOG Performance Status 0, 1 or 2. Exclusion Criteria: Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation. Use of a tricyclic antidepressant or monoamine oxidase inhibitor within 14 days prior to registration. Current untreated or unhealed oral candidiasis or oral herpes simplex virus infection. Untreated narrow angle glaucoma within 6 weeks prior to registration. Untreated urinary retention within 6 weeks prior to registration. Administration of cryotherapy to prevent oral mucositis within 6 weeks prior to registration. Current serious heart disease or a recent history of myocardial infarction. Current untreated or unresolved conditions like epilepsy, hyperthyroidism, hepatic dysfunction, delirium, and neutropenia. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: doxepin solution<br>Patients received a doxepin solution spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a placebo spray was administered to the posterior pharyngeal wall 10 minutes before eating. | Drug: doxepin solution<br>* 2.0 mL doxepin solution (5mg/mL) sprayed to the posterior pharyngeal wall<br>|
| Placebo Comparator: placebo<br>Patients received a placebo spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a doxepin solution spray was administered to the posterior pharyngeal wall 10 minutes before eating. | Other: Placebo<br>* 2.0 mL placebo sprayed to the posterior pharyngeal wall<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Redution of swallowing-induced pain | The redution of swallowing-induced pain was measured by the numerical analogue scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 10, 20, 30, 60 minutes after assigned administration. | Baseline, and 10, 20, 30, 60 minutes after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Drowsiness Increase | The total drowsiness increase was measured by the numerical analogue scale of 0 to 10, with 0=no drowsiness and 10=extreme drowsiness in the questionnaires taken at baseline, and 10, 20, 30, 60 minutes after assigned administration. | Baseline, and 10, 20, 30, 60 minutes after administration | 
| Total Taste of the Agent | The total taste of the agent was measured by the numerical analogue scale of 0 to 10, with 0=acceptable and 10=terrible in the questionnaires taken at 10, 20, 30 and 60 minutes after assigned administration. | 10, 20, 30 and 60 minutes after administration | 
| Total Stinging or Burning From the Agent | The stinging or burning of the oral cavity/oropharynx was measured by the numerical analogue scale of 0 to 10, with 0=no stinging or burning and 10=worst stinging or burning in the questionnaires taken at 10, 20, 30 and 60 minutes after assigned administration. | 10, 20, 30 and 60 minutes after administration | 
| Difficulty in Swallowing Different Food | The difficulty in swallowing liquids, pureed food and solid food was measured respectively by the numerical analogue scale of 0 to 10, with 0=not at all and 10=very much in the questionnaires taken at 10, 20, 30 and 60 minutes after assigned administration. | Baseline, and 10, 20, 30, 60 minutes after administration | 
| Patient Preference for Continuing Therapy With the Agent | Patients were asked if they would like to continue treatment with that particular agent at 60 minutes after assigned administration. | 60 minutes after administration | 
| Adverse Event Profiles | Adverse events were assessed and record using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. | up to one day after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasopharyngeal carcinoma, Oral mucositis, Radiotherapy, Swallowing-induced pain, Doxepin