Transcutaneous carbon dioxide therapy significantly accelerates diabetic foot ulcer healingFrangež, Igor (Avtor) Potkonjak, Miloš (Avtor) Skender, Veliu (Avtor) Metelko, Željko (Avtor) Badanjak, Anica (Avtor) Križaj, Julija (Avtor) Ban Frangež, Helena (Avtor) Poljičanin, Tamara (Avtor) Meloni, Marco (Avtor) Papanas, Nikolaos (Avtor) Bulum, Tomislav (Avtor) transcutaneous CO2 therapydiabetic foot ulcerwound healingchronic woundBackground/Objectives: Diabetic foot ulcers (DFUs) represent common and severe complications of diabetes mellitus (DM). The aim of our parallel-group, open-label, superiority, multicentre randomised controlled trial (RCT) was to evaluate the effectiveness of transcutaneous gaseous carbon dioxide therapy (hereinafter CO2 therapy) in ulcer healing in patients with non-healing DFUs. Methods: A total of 115 participants (89 males and 26 females, aged 65.7 ± 10.9 years) with a non-healing DFU were randomised to the intervention (76 participants) and control (39 participants) group. Participants in the intervention group received standard of care, combined with CO2 therapies administered every weekday for four consecutive weeks. Participants in the control group received only standard of care. Results: After 4 weeks, 49 (64.5%) ulcers in the intervention group healed, compared with three (7.7%) in the control group (primary outcome). The percentage ulcer area reduction from baseline (secondary outcome) was significantly larger (p ≤ 0.001) in patients from the intervention group, with the median value 100% (18.4–100%), compared to the patients from the control group, with the median value 40% (−300–100%). Patients receiving CO2 therapy had 35.4-fold higher odds of ulcer healing versus controls (OR 35.4, 95% CI 6.68–187.53; p < 0.001), and in multivariate logistic regression, CO2 therapy remained independently associated with healing, while larger baseline ulcer area was associated with lower odds of healing (OR 0.654, 95% CI 0.438–0.977; p = 0.038). No adverse effects were reported. Conclusions: CO2 therapy significantly contributes to ulcer healing in patients with non-healing DFUs, with no observable adverse effects, demonstrating significant potential as an effective and safe complementary treatment of DFUs in conjunction with standard of care.20262026-04-07 13:28:15Neznano28785sl