A comparison of silymarin vs benzydamine rinse in the prevention of radiation-induced oropharyngeal mucositis in head and neck cancers: A randomized controlled trial

Comparison of the effect of silymarin mouthwash with benzydamine mouthwash in the prevention of grade 3 radiation-induced acute mucositis with doses above 50 Gy in head and neck squamous cell carcinoma until the end of treatment

A randomized, parallel group, double-blind phase 3 controlled trial of 98 patients. Randomization was carried using Sealed Envelope website (sealedenvelope.com).

The study population are head and neck squamous cell carcinoma patients of Shahid Rajaei hospital in Babolsar, who will be treated with head and neck radiotherapy for the first time. The researchers, treating physicians, and the patients are blinded

Inclusion Criteria: patients with head and neck squamous cell carcinoma, receiving at least 50 Gy radiation to 2 of the 4 areas of the head and neck including the oral cavity, oropharynx, hypopharynx and larynx Exclusion Criteria: History of severe allergy to silymarin, benzydamine or other NSAIDs, Narcotic use in the last month (even once), History of radiation therapy to the same target areas, Presence of mucositis on admission, History of dry mouth, Proven dementia or history of uncontrolled psychiatric disease, Pregnancy, Malnutrition

Arm A receives Silymarin mouthwash, Arm B receives Benzydamine mouthwash

Grade 3 mucositis (according to Common Terminology Criteria for Adverse Events (CTCAE) v.5

Permuted block randomization with a block size of 4 individual was carried out on Sealed Envelope website (www.sealedenvelope.com) and its Excel output file with three letter codes is only available to the study pharmacist who is based outside the hospital and is completely separate from the study process. Patients are stratified in terms of receiving/not receiving concurrent chemotherapy. The pharmacist of the study prepares the silymarin and benzydamine mouthwashes, which are completely similar in terms of color, smell, taste and consistency, and packs them into completely similar colorless 250 cc graduated bottles and sticks the three-letter codes on the bottles of treatment arms: A (silymarin ) and B (benzidamine). Next, the codes assigned to the strata (chemotherapy and no-chemotherapy) are printed with consecutive numbers (from 1 to 49 for each strata) and provided to the principal investigator. After determining the treatment plan by the treating physician, eligible patients are referred to the principal investigator. Following acceptance of the study conditions and signing the informed consent form, they will receive their drug with the dedicated strata bottle code in sequence (i.e. from 1 to 49). Each patient receives a total of 10 bottles with the same code; one or two bottles delivered each week.

The three letter codes assigned to each strata (chemotherapy and no-chemotherapy) are printed with consecutive numbers (from 1 to 49 for each strata) and provided to the principal investigator, which in turn prints out each number with it's unique three letter code on a discrete paper. Then papers are enveloped and numbered from 1 to 49. Eligible patients in each strata are sequentially provided bottles starting from number 1 by admission order. The corresponding codes for each patient is recorded and delivered to the pharmacist on a weekly basis.

All of the deidentified data are to be released after publication of the study

Within one year after paper publication

Any academic institution can have access to data

There is no restriction

Any interested institution is expected to send a formal email to the Health Research Institute of Babol University of Medical Sciences. Email: hribabol@gmail.com Phone & Fax: +98-11-32190557 Website: hri.mubabol.ac.ir

The documents would be delivered to the applicant by email, after one business week. In some cases, a Research Vice Chancellor and/or Ethics Committee approval for data access may be needed in which the aforementioned time may stretch up to three weeks. Applicants are not required to do additional tasks in such cases.