Benzydamine for Radiation-Induced Oral Mucositis in Patients Receiving High-Dose Radiotherapy

The Effect of 0.15% Benzydamine Hydrochloride (Difflam) Oral Spray on the Severity of Radiation-induced Oral Mucositis in Patients Receiving High-Dose Radiotherapy: An Open-Label Randomized Clinical Trial

This single-center, open-label, randomized clinical trial evaluates the effect of 0.15% benzydamine hydrochloride (Difflam) oral spray on the severity of radiation-induced oral mucositis in patients with head and neck cancer receiving high-dose radiotherapy (≥50 Gy) without concurrent chemotherapy. Oral mucositis is a common and clinically significant complication of radiotherapy that can cause pain, difficulty swallowing, nutritional impairment, and treatment interruption.

Participants are randomly assigned to receive either standard oral care alone or standard oral care plus benzydamine oral spray for 6 weeks. Oral mucositis severity is assessed weekly using the World Health Organization (WHO) oral mucositis grading scale. The study aims to determine whether benzydamine reduces the progression and severity of oral mucositis in this patient population.

Study Overview

• Status: Completed
• Conditions: Radiation-induced Oral Mucositis
• Intervention / Treatment: Drug: benzydamine hydrochloride; Other: saline mouth rinse

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 4

Contacts and Locations

Study Locations

• Syria
  • Latakia, Syria
    • Pharmacy, Latakia university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 22 years or older
• Pathologically confirmed head and neck cancer
• Currently undergoing RT
• Cumulative total radiation dose exceeding 50 Gy
• Patients were enrolled in the study after their diagnosis of OM was confirmed by a specialist, which occurred approximately two weeks after the initiation of radiotherapy
• All subjects had grade 1 OM according to the WHO criteria at baseline, except for two patients in the intervention group who presented with grade 2 severity at the start of the study
• None of participants received concurrent chemotherapy during the study period

Exclusion Criteria:

• Use of concurrent treatments affecting OM
• Incomplete follow-up
• Other conditions influencing its progression
• patient withdrawal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benzydamine plus standard oral care; participants in this arm received standard oral care, including routine oral hygiene measures and saline mouth rinses, in addition to 0.15% benzydamine hydrochloride oral spray for 6 weeks.	Drug: benzydamine hydrochloride; Benzydamine hydrochloride 0.15% oral spray administered as 4 to 8 sprays, 4 to 6 times daily, for 6 weeks, in addition to standard oral care; Other: saline mouth rinse; standard oral care consisted of routine oral hygiene measures and saline mouth rinses.
Active Comparator: Standard oral care alone; participants in this arm received standard oral care alone, including routine oral hygiene measures and saline mouth rinses, without benzydamine oral spray.	Other: saline mouth rinse; standard oral care consisted of routine oral hygiene measures and saline mouth rinses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly severity of oral mucositis	Oral mucositis severity was assessed weekly for 6 weeks by a specialist using the World Health Organization (WHO) oral mucositis grading scale. The scale ranges from 0 to 4, where 0 indicates no mucositis and 4 indicates sever mucositis. Higher represent worse severity.	Weekly for 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who developed grade 3 oral mucositis	The proportion of patients who developed grade 3 oral mucositis during the 6-week follow-up period was assessed using the World Health Organization (WHO) oral mucositis grading scale.	During the 6-week follow-up period
Between-group difference in oral mucositis severity at weeks 4 and 6	Between-group differences in oral mucositis severity were assessed at week 4 and week 6 using the World Health Organization (WHO) oral mucositis grading scale. The scale ranges from 0 to 4, where 0 indicates no mucositis and 4 indicates sever mucositis. Higher represent worse severity.	Week 4 and week 6

Collaborators and Investigators

• Sponsor: Tishreen University
• Investigators: Study Director: Rama Ibrahim, PhD, Latakia university, Latakia, Syria; Principal Investigator: Bassam Saad, PhD, Latakia university, Latakia, Syria

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2025
• Primary Completion (Actual): December 25, 2025
• Study Completion (Actual): December 25, 2025

Study Registration Dates

• First Submitted: March 8, 2026
• First Submitted That Met QC Criteria: March 8, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Supportive care; Benzydamine; Radiation-induced oral mucositis; Head and neck cnacer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Indazoles; Pyrazoles; Benzydamine
• Other Study ID Numbers: LATAKIA-ONC-BENZ-2025-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No