Double-Blind Clinical Trial Evaluating the Effectiveness of Amphotericin B Mouthwash versus an Antacid–Nystatin–Diphenhydramine Mouthwash for Chemotherapy-Induced Mucositis in Pediatric Patients

Comparison of Amphotericin B Mouthwash versus Antacid–Nystatin–Diphenhydramine Mouthwash in Chemotherapy-Induced Mucositis in Children

Phase 3, parallel, double-blind randomized controlled trial enrolled 40 participants (20 per group)

This double-blind randomized trial was conducted in Bushehr on patients with chemotherapy-induced oral mucositis, allocated by block randomization to intervention or control groups and followed for 21 days, with mucositis severity and lesion size recorded at each visit.

With ethical approval, IRCT registration, and university authorization obtained, the inclusion criteria are: children aged 6 to 18 years with chemotherapy-induced oral mucositis (grade 2 or 3), parental consent and child assent, and absence of other local causes. Exclusion criteria include hypersensitivity to the study drugs and inability to perform mouth rinsing.

Participants were randomized into two groups. Group A received a compounded mouthwash of diphenhydramine (5 mL, Darou Pakhsh, Tehran), antacid (5 mL, Loghman, Tehran), and nystatin (1 mL, 100,000 IU, Jaber Ebne Hayyan, Tehran). Group B received amphotericin B (50 mg, Exir, Boroujerd) in 500 mL of 5% dextrose. Both groups used 7 mL three times daily for 21 days. Children able to gargle rinsed for 2 minutes and repeated after 15 minutes; in younger children, the solution was applied with sterile gauze. Mouthwashes were freshly prepared every three days, participants were instructed not to swallow and to avoid food or drink for 30 minutes, and both formulations were dispensed in identical coded bottles to maintain blinding.

Resolution time of oral mucositis

Participants will be randomly assigned to two intervention groups using block randomization with a block size of four to ensure balanced allocation. An independent statistician will generate the block randomization scheme using the free website, http://randomization.com. Allocation concealment will be maintained through the use of sequentially numbered, opaque, sealed envelopes (SNOSE) to prevent selection bias. After enrollment, a nurse not involved in the intervention or outcome assessment will sequentially open the next envelope to assign the participant to either Group A or Group B. The treating physician, responsible for preparing and administering the mouthwashes, will be aware of the group assignments for operational purposes but will not participate in outcome evaluations.

The pediatric dental specialist conducting mucositis assessments will be blinded to group allocations to ensure unbiased outcome evaluations. Study participants, their legal guardians, and data analysts will remain blinded to the treatment assignments. Both mouthwashes will be dispensed in identical containers with neutral labeling to prevent detection of group assignment by participants or caregivers. Blinding effectiveness will be assessed midway through the study by querying assessors and participants regarding their perception of group allocation.