Transcutaneous CO ₂ Therapy Improves Tissue Oxygenation, Ulcer Healing and Pain in Recurrent Hard-to-Heal Diabetic Foot Ulcers: A Randomized Controlled Trial

This trial evaluates whether transcutaneous gaseous carbon dioxide therapy (CO 2 therapy) combined with standard of care (SOC) improves healing of hard-to-heal recurrent diabetic foot ulcers (DFUs) compared with SOC alone. A total of 30 participants with recurrent hard-to-heal DFUs were included and randomized 1:1 to an intervention (CO 2 therapy plus SOC) or a control group (SOC only). The intervention consisted of 20 daily 50-minute CO 2 therapy sessions over 4 weeks. After 4 weeks, 46.7% of ulcers in the intervention group were completely healed, versus 0% in the control group (p = 0.005). The intervention group showed a median area reduction of 85.7% (IQR 54.9–100) compared to 17.2% (IQR 0.88–33.5) in controls (p < 0.001), with significantly better Falanga wound-bed scores (p < 0.001). The intervention group demonstrated a significant relative increase in StO 2 (29.6 ± 19.6%), whereas the control group exhibited a decrease (-2.2 ± 6.9%), resulting in a between-group difference of 31.8% (95% CI 20.5%–43.0%; p < 0.001). Pain intensity significantly decreased in the intervention group only (p = 0.002). This trial suggests that CO 2 therapy in combination with SOC is superior to SOC alone in healing recurrent, hard-to-heal DFUs.