# Transcutaneous Carbon Dioxide Therapy Significantly Accelerates Diabetic Foot Ulcer Healing: A Multicentre Randomised Controlled Trial

## TL;DR

A study finds that carbon dioxide therapy, when added to standard care, significantly improves healing of diabetic foot ulcers without causing adverse effects.

## Contribution

This is the first multicentre RCT demonstrating that transcutaneous CO2 therapy accelerates healing of non-healing diabetic foot ulcers.

## Key findings

- 49 (64.5%) ulcers healed in the CO2 therapy group after 4 weeks, compared to only 3 (7.7%) in the control group.
- CO2 therapy was associated with a 35.4-fold higher odds of ulcer healing compared to standard care alone.
- No adverse effects were reported in patients receiving CO2 therapy.

## Abstract

Background/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.