Cabrera-Jaime, S., Martinez, C., Ferro-Garcia, T., Giner-Boya, P., Icart-Isern, T., Estrada-Masllorens, J.M., & Fernandez-Ortega, P. (2018). Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5% solution in the treatment of oral mucositis in cancer patients with solid tumour: A feasibility randomised triple-blind phase III clinical trial. European Journal of Oncology Nursing, 32, 40–47.

To evaluate/compare three treatments for oral mucositis: (1) Plantago major extract mouthwash, (2) chlorhexidine 0.12%, and (3) aqueous solution of 5% sodium bicarbonate for  the treatment of oral mucositis in patients with solid tumors. Evaluation points included healing time, pain, oral intake, and quality of life.

Randomized controlled trial (phase 3)

• Group A: Control group, received standard of care which included sodium bicarbonate 5% aqueous solution with an additional dose of sodium bicarbonate 5% aqueous solution. 
• Group B: Experimental group, received sodium bicarbonate 5% aqueous solution plus Plantago major extract
• Group C: Experimental group, received sodium bicarbonate 5% aqueous solution plus chlorhexidine 0.12%

The treatment was 14 days for all groups. All groups received education regarding the management of mucositis, a set of instructions, a diary to record signs and symptoms of mucositis, and instruction for proper storing of the mouthwashes. All participants were instructed to rinse with 8 ml of solution for two minutes every six hours. They were instructed to leave 15 minutes between the two mouthwashes.

• N = 50 (evaluable)   
• AGE: Mean age = 59.5 years (SD = 14.3)
• MALES: 48%  
• FEMALES: 52%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Tumor types: breast (30.6%), colorectal (32.7%), lung (14.3%), gastric (8.2%) and other (14.2%)
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had a mean of 3.6 (SD = 3.2) chemotherapy cycles prior to oral mucositis outbreak. Patients received many different chemotherapy drugs. No participants developed neutropenia.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Spain

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Randomized controlled trial; investigators, participants, care providers, and statistician were all blinded.

• WHO mucositis scale
• Visual analogue scale (VAS) for pain intensity
• Intake capacity was captured by asking the participants if they could tolerated liquids only or liquids and solids. 
• European Organizsation for Research and Treatment of Cancer Quality of Life Core 30 Questionnaire (EORTC QLQ-C30)
• CBC (evaluation of neutropenia)
• Patient diary

• Healing time: No statistical difference between groups. The group that used the double 5% sodium bicarbonate solution did have a shorter time to heal by two days, which may be clinically significant. 
• Pain intensity: No significant difference
• Oral intake capacity: No significant difference
• Quality of life: No significant difference

In this small group, there is no advantage in using a chlorhexidine or Plantago major extract mouthwash in comparison to a double sodium bicarbonate solution. The latter is likely less expensive and more readily available

• Small sample (< 100)
• Findings not generalizable
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Not generalizable to those patients who become neutropenic or patients with non-solid tumors. Potentially some bias as there was self-reporting of oral intake versus an objective measure. Attrition rate 16% (failure to follow through with monitoring, interruption of the intervention)

This study does not support the use of Plantago major or chlorhexidine mouthwashes over double doses of sodium bicarbonate 5% aqueous solution.