Getting a wound closed is a milestone. The next question is how much life we can help a person reclaim before the next wound and moving patients into more ulcer-free, hospital-free, and activity-rich days in remission.
Our long-time friend and colleague John Steinberg and coauthors Dot Weir, Michael Pierides, Barry Rosenblum, and Kathleen Ozsvath bring that question into focus in their new review in the Journal of Wound Care. The subject is intermittent cyclically pressurised topical wound oxygen, or CPTWO, and the possibility of more durable healing.
This is a narrative review of existing evidence, including seven clinical studies representing 3,567 unique patients. It examines a particular oxygen-delivery approach. Continuous-diffusion devices and systemic hyperbaric oxygen have different delivery methods and evidence bases.
A remission conversation years in the making
We explored prevention and remission here in 2012, ahead of the paper Joe Mills and I published in 2013. The point was practical: a healed foot still needs protection, surveillance, and rapid access to care.
Our 2017 review with Andrew Boulton and Sicco Bus, also featured on this blog, described recurrence approaching 40% within one year and 65% within five years. Those population estimates explain why the period after closure deserves so much attention. They are not a control group against which we can casually compare a new device registry.
By 2019, we were discussing ulcer-free survival days: the accumulated time a person spends healed. That remains a useful way to judge progress. A wound photograph captures a moment; patients live through everything between those photographs.
The randomized trial: three different questions
The pivotal TWO2 trial by Robert Frykberg and colleagues randomized 73 people with hard-to-heal diabetic foot ulcers to active CPTWO or sham treatment, both alongside standard care. It stopped at its first prespecified efficacy analysis.
Initial healing: at 12 weeks, 15/36 ulcers (41.7%) had closed with active treatment versus 5/37 (13.5%) with sham. That is a 28.2-percentage-point absolute difference. The odds ratio was 4.57, with a wide 97.8% confidence interval of 1.19–17.57.
Later healing status: at 12 months after enrollment, 20/36 (55.6%) versus 10/37 (27.0%) index ulcers were closed. This is encouraging longer-term follow-up, but does not mean those ulcers stayed continuously closed for 12 months.
Recurrence after early healing: the separate comparison was 1/15 versus 2/5 recurrent index ulcers (P=.070). Only 20 early healers contributed, and selecting people on the basis of healing weakens the protection of randomization. This exploratory signal warrants a larger recurrence-focused trial.
These endpoints answer different questions. The most secure finding is improved healing in this selected population; the size and durability of any recurrence-prevention benefit remain uncertain.
Study treatment ended at closure or 12 weeks. The trial did not test routine oxygen treatment throughout remission, or directly quantify additional ulcer-free days.
The real-world studies deserve a careful read
The review’s largest cohort, Lohr and colleagues’ retrospective series, analyzed 3,126 people with mixed lower-extremity wounds. Of these, 2,027 healed; 54 of those healed patients (2.7%) subsequently required recurrence-related retreatment. That is an interesting service-level observation. Retreatment records, however, will not necessarily capture every recurrent or new ulcer. The analysis excluded ongoing treatment, incomplete records, and nonmedical discontinuations, and had no concurrent control group.
In Yellin and colleagues’ matched Veterans Affairs cohorts, wound-related hospitalizations occurred in 5/70 CPTWO-treated patients versus 28/70 controls, and amputations in 6/70 versus 22/70 within 360 days. These important associations merit prospective testing. Treatment selection and other therapies could influence the results; the study did not assess wound healing or wound-specific recurrence.
The longest recurrence follow-up comes from Tawfick and Sultan’s venous-ulcer study: recurrence among healed ulcers was 3/51 versus 14/30 at 36 months. Allocation reflected patient preference, and both groups received maintenance compression. This is encouraging observational evidence in venous disease, with a different biology and care pathway from diabetic foot ulceration.
How this fits our work and the wider evidence
Our own oxygen work includes the 2018 randomized trial with Mark Niederauer and colleagues. Among 146 participants, continuous-diffusion oxygen produced 12-week closure in 32.4% versus 16.7% with placebo. That was a different technology from CPTWO, reinforcing the need to name the modality when discussing results.
In the 2023 systematic review I coauthored with Marissa Carter and colleagues, four randomized trials yielded a pooled healing risk ratio of 1.59 (95% CI 1.07–2.37), with moderate overall certainty. This supports adjunctive topical oxygen for selected chronic ulcers, chiefly in adequately perfused, uninfected populations. Pooling several technologies cannot establish that one device is superior or that all extend remission.
Readers may remember our coverage of the 2021 review from Jonathan Golledge’s team and the 2022 update by Xian-Kun Sun and colleagues. The healing evidence has accumulated over time. Durability has also been explored with other modalities, including a small continuous-diffusion oxygen follow-up study; it is still a much thinner evidence base.
An adjunct inside a limb-preservation system
Oxygen supports repair biology, and cyclical pressure may help address edema. The proposed link to stronger, more durable repaired tissue is plausible, but has not been directly demonstrated as the cause of the clinical outcomes in these studies.
The ADA’s 2026 Standards of Care recommend considering randomized-trial-supported adjuncts, including topical oxygen, when optimal standard care has failed. The 2023 IWGDF wound-healing guideline makes a conditional topical-oxygen recommendation based on low-certainty evidence. Neither establishes a device-specific recurrence-prevention claim.
In practice, the essentials travel together: vascular assessment and revascularization when indicated, effective offloading, debridement, infection treatment, appropriate dressings, and attention to the person’s ability to carry out the plan. After closure, protective footwear, surveillance, and prompt assessment of new problems continue. Home-based therapy may help some people, but treatment burden, access, cost, and adherence deserve to be measured too.
Let’s count the days we give back
The next studies should begin with a clear definition of remission and track both recurrence at the original site and new ulcers elsewhere. They should measure ulcer-free days, hospitalization, amputation, walking, and quality of life, while accounting for death and loss to follow-up. Initial closure, sustained closure, and a patient’s overall ulcer-free time should each have their own place in the analysis.
John, Dot, Michael, Barry, and Kathleen deserve congratulations for bringing durability into sharper focus. Topical oxygen has credible healing evidence and promising longer-term signals. The opportunity now is to demonstrate how much additional ulcer-free, hospital-free, activity-rich time we can give back to our patients.
Study context: The Steinberg review reports no conflicts of interest. The TWO2 randomized trial and the Yellin observational study received manufacturer support. I coauthored the 2018 continuous-diffusion trial and 2023 meta-analysis cited above; readers can consult those papers for their study-specific disclosures.
Featured paper: Steinberg J, Weir D, Pierides M, Rosenblum B, Ozsvath K. Review and analysis of healing durability in lower extremity wounds treated with intermittent cyclically pressurised topical wound oxygen. Journal of Wound Care. 2026;35(10):856–867. doi:10.12968/jowc.2026.0475.
#ActAgainstAmputation #DiabeticFoot #Remission #WoundHealing #LimbPreservation
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