Effectiveness and cost-effectiveness of ozone treatment in patients with paraesthesia (numbness, tingling) secondary to chemotherapy-induced peripheral neuropathy: randomized, triple-blind clinical trial (OzoParQT)

Abstract

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, disabling side effect of taxanes and platinum drugs, often compromising quality of life and treatment continuity. Existing therapies are few and largely ineffective. Given this unmet need, our prior experience suggests ozone therapy may offer clinical benefit as an adjuvant treatment. Methods OzoParQT is a Phase II-III randomized, triple-blind trial including 42 adults (>= 18 years) with any cancer and Grade >= 2 CIPN (numbness and/or tingling) lasting >= 3 months. Eligible patients must be off neurotoxic chemotherapy for >= 3 months, with stable/remitted disease and >= 6-month life expectancy. Participants will be randomized (1:1) to Ozone or Control (placebo) groups. All patients will continue standard care by their oncologists and undergo 40 rectal insufflation sessions over 16 weeks (3 & times;/week for 8 weeks, then 2 & times;/week). The Ozone group receives O-3/O-2 (10-30 & micro;g/mL); the Control group receives O-2 (O-3/O-2: 0 & micro;g/mL). Volumes range from 180 to 300 mL as tolerated. The primary objectives are to evaluate the effect of adding ozone on change from baseline at week 28 (end of follow-up) in: i) patients' self-perceived level of paraesthesia (numbness and/or tingling), and ii) patients' self-perceived health-related quality of life (HRQoL). Secondary objectives include evaluating the effect of ozone on: i) additional direct costs, ii) evolution of neuropathy symptoms (CTCAE v5.0, QLQ-CIPN20), iii) evolution of quality of life (EQ-5D-5L, and QLQ-C30), iv) evolution of anxiety and depression, v) evolution of biochemical parameters related to oxidative stress and chronic inflammation, vi) evolution of infrared images and spectral signatures (450 to 900 nm) in hyperspectral images obtained from hands and feet, and vii) toxicity of rectal ozone treatment. Except for direct costs and toxicity, all variables will be assessed at week 16 (end of insufflations) and week 28 (end of follow-up). Masking will be triple: participant, care provider, and outcomes assessor. Discussion This study aims to provide robust evidence on the effectiveness and cost-effectiveness of ozone therapy as an adjuvant treatment for CIPN, a condition with very limited therapeutic options.The trial will clarify whether ozone therapy can significantly improve patient-reported symptoms and quality of life, potentially leading to a new management strategy with low morbidity.