Topical Oxygen Therapy Meta-Analyses

Topical Oxygen Therapy for Diabetic Foot Ulcers: Updated Evidence From Randomised Trials

Systematic review and meta-analysis of 3 RCTs including 325 patients.

Key findings:

• Across cTOT/CDO randomized trials with a 12-week assessment, cTOT / CDO used alongside standard care increases the likelihood of complete closure in DFUs.
• Within comprehensive DFU care (debridement, infection control, moisture balance, off-loading),cTOT / CDO can be considered to increase 12-week closure.
• Higher oxygen tension at the wound interface supports collagen synthesis, keratinocyte migration, angiogenesis, and host antimicrobial responses.
• This review does not include iTOT (TWO₂) so the opinions and conclusions are pertinent to continuous topical oxygen only. 

Citation: G. Theodorakopoulos and D. G. Armstrong, “Topical Oxygen Therapy for Diabetic Foot Ulcers: Updated Evidence From Randomised Trials,” Wound Repair and Regeneration34, no. 3 (2026): e70170, https://doi.org/10.1111/wrr.70170.

Effects of different treatment measures on the efficacy of diabetic foot ulcers: a network meta-analysis

Systematic review and meta-analysis of 57 DFU RCTs including 4,826 patients (5 DFU RCTs and 461 patients for Topical Oxygen Therapy)

Key findings:

• Observations compared to standard of care (SoC), PRP, HBOT, TOT, ADM, and Scs showed higher ulcer healing rates.
• SUCRA ranking results suggest that both HBOT and TOT treatments are superior to SoC in all aspects of the study.
• Due to the particularity of DFUs, SoC is not effective, but the new treatment scheme has a remarkable effect in many aspects.
• Treatment of DFU is not a single choice, combined methods often achieve better efficacy, and will not bring more adverse reactions.

Citation: OuYang H, Yang J, Wan H, et al. (2024) Effects of different treatment measures on the efficacy of diabetic foot ulcers: a network meta-analysis. Front. Endocrinol, 15:1452192.

The efficacy of topical oxygen therapy for wound healing: A meta-analysis of randomized controlled trials and observational studies

Systematic review and meta-analysis of 7 DFU RCTs, including 692 patients, and 2 controlled observational studies (n=111).

Key findings:

• The rate of healed wounds was 25.8% in the control group and 43.25% in the adjuvant TOT group, which shows the use of TOT significantly increased the number of healed wounds.
• A significant decrease in the percentage of wound area was found in the TOT group in RCT studies.
• The rate of healed wounds in the observational studies was 37.5% in the standard care group and 80.95% in the adjuvant TOT group, which shows a significant increase in the number of healed wounds in the adjuvant TOT group.

Citation: Putri IL, Alyssa A, Aisyah IF, et al. (2024) The efficacy of topical oxygen therapy for wound healing: A meta-analysis of randomized controlled trials and observational studies. Int Wound J, 21(7): e14960.

Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis

Systematic review and meta-analysis of 31 RCTs including 1,823 patients.

Key findings:

Pooled effects of 31 included studies showed that patients treated with oxygen:

• had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987)
• a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599)
• lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862)
• shorter wound healing time (SMD, −0.705; 95% CI, −0.908 to −0.501)
• higher post-study TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group.

Citation: Du X, Zhang X, Liu J, et al. (2024) Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis. Adv Skin Wound Care, 37(5):1-9.

Systematic review of the effects of topical oxygen therapy on wound healing

Systematic review of 10 RCTs and 12 non-RCTs on the effects of topical oxygen therapy in wound healing.

Key findings:

• 7 double-armed: Healing rates, n= 725. Significant difference in TOT group that healed (95% CI; p=<.001)
• 9 single-armed: 1,195/4,273 completely healed (95% CI; p= <.001)
• 2 double-armed: Wound recurrence in 101 patients included decreased recurrence rate in TOT group (95% CI; p=<.001)

Citation: Nagarsheth K, Kankaria A, Marsella J, et al. (2024). Systematic review of the effects of topical oxygen therapy on wound healing. JVS-Vascular Insights, 2:100051.

Efficacy and safety of topical oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis

Systematic review and meta-analysis of 7 DFU RCTs including 614 patients.

Existing evidence suggests that TOT is effective and safe for chronic DFUs.

Compared with the control group, the TOT group had a higher healing rate (RR=1.63, 95% CI 1.33, 2.00, p<.00001).

Citation: Sun XK, Li R, Yang XL, et al. (2022) Efficacy and safety of topical oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis. Int Wound J, 19(8):2200-9.

Topical oxygen therapy for healing diabetic foot ulcers: A systematic review and meta-analysis of randomized control trials

Systematic review and meta-analysis of 4 DFU RCTs including 492 patients.

Key findings:

• TOT increased the likelihood of healing by 59% within 12 weeks.
• Use of adjunctive TOT significantly increased the healing rate (RR: 1.59; 95% Cl: 1.07, 2.37; p<0.02).

Citation: Sethi A, Khambhayta Y, Vas P. (2022) Topical oxygen therapy for healing diabetic foot ulcers: A systematic review and meta-analysis of randomized control trials. Health Sci Rev, 3(2022-Jun):100028.

Efficacy of topical wound oxygen therapy in healing chronic diabetic foot ulcers: Systematic review and meta-analysis

Systematic review and meta-analysis of 4 DFU RCTs including 494 patients.

Key findings:

• TOT recognized as a potential adjunctive therapy for the treatment of DFUs.
• Random-effects meta-analysis of four RCTs showed that TOT improved wound healing at 12-weeks over SOC alone (RR: 1.59; 95% Cl: 1.07-2.37; p=0.021).
• Overall GRADE level of evidence for TOT was moderate.

Citation: Carter M, Frykberg RG, Oropallo A, et al.(2022) Efficacy of Topical Wound Oxygen Therapy in Healing Chronic Diabetic Foot Ulcers: Systematic Review and Meta-Analysis. Adv Wound Care, 12(4):177-86.

Topical oxygen therapy for diabetes-related foot ulcers: A systematic review and meta-analysis

Systematic review and meta-analysis of 6 DFU RCTs including 530 patients.

Key findings:

Meta-analysis suggests TOT significantly increased the likelihood of ulcer healing compared to controls (RR=1.94, 95% CI 1.19, 3.17; I2=57%; NNT=5.33).

Citation: Thanigaimani S, Singh T, Golledge J.
(2021) Topical oxygen therapy for
diabetes- related foot ulcers: A systematic
review and meta-analysis. Diabet Med,
2021;00:e14585.

Impact of topical oxygen therapy on diabetic foot ulcer healing rates: a systematic review

Systematic review and meta-analysis of 4 DFU RCTs.

Key findings:

• DFUs are >2x more likely to heal with TOT than SOC alone.
• Time to 50% DFU closure was significantly shorter for participants who received TOT.
• OR=2.49 (95% CI 1.59-3.90, p=.00001).

Citation: Connaghan F, Avsar P, Patton D, et al. (2021) Impact of topical oxygen therapy
on diabetic foot ulcer healing rates: a
systematic review. [Abstract] J Wound
Care, 30(10):823-9.