2804 - A Randomized, Prospective Trial of Hydrogen-Rich Water (HRW) to Mitigate Acute Mucositis during Radiation Therapy

Purpose/Objective(s): Radiation is a mainstay of therapy for head/neck cancer. However, patients invariably develop mucositis along the targeted subsite, which persists during and after treatment, leading to weight loss, hospital admissions and potentially treatment interruptions. Hydrogen-rich water (HRW) is an available supplement that is thought to scavenge free radicals and confer anti-inflammatory effects. In this study, we prospectively evaluated the use of HRW to mitigate radiation-induced mucositis in a randomized, double-blind, placebo-controlled trial.

Materials/Methods: Patients who were receiving radiation or chemoradiation to the head/neck were eligible to enroll and randomized in a 1:1 ratio to receive HRW or placebo. The study drug was provided as a dissolvable tablet dispensed by our central pharmacy. Subjects were instructed to drop 1 study tablet in room temperature water, and drink the fizzy solution promptly, twice daily while on radiation therapy. The placebo tablets were of the same size and dissolved similarly. Patients were evaluated at baseline pre-treatment, on weekly on-treatment visits (OTVs), and at a short-interval (1 month) and long-interval (3 month) post-treatment visit with a brief pain inventory (BPI), vital signs/physical exam, clinical photos, and assessment of CTCAE grade of mucositis and other side effects. Compliance was assessed with a pill diary and collection of remaining tablets once done with therapy. The primary endpoint was the incidence of CTCAE grade 3 mucositis or higher throughout the treatment course. Secondary endpoints included quality-of-life (QOL) measures utilizing patient reported outcomes (PRO). An interim analysis was pre-planned to assess for futility in the experimental arm (grade 3 mucositis > 60%).

Results: After obtaining IRB approval, 24 patients were enrolled between 2022-2024, of which 18 were evaluable, 9 in each arm (patients were evaluated if they consumed at least 1 dose of the study drug during treatment). The subsites of the head/neck included oropharynx (10, 56%), larynx (4, 22%), oral cavity (3, 16%) and nasopharynx (1, 6%). The vast majority received concurrent chemotherapy (15, 83%). All patients completed their radiation courses but compliance with the study drug was variable - 6 patients (67%) of the HRW arm took more than half of the provided doses, while 2 (22%) of the placebo arm did. The incidence of CTCAE grade 3 mucositis was higher in the placebo arm (4, 44%) versus the HRW arm (2, 22%). This result was not statistically significant by Fisher’s Exact Test (p=0.6199) though neither arm met futility criteria.

Conclusion: HRW was associated with a numerically lower incidence of CTCAE grade 3 mucositis in this small interim trial cohort. However, both HRW and placebo had lower grade 3 rates than expected by historical comparisons. The placebo appeared to be somewhat poorly tolerated indicated by lower compliance, perhaps limiting the accuracy of this randomized comparison. IRB #2022-00167.