Chronic wound? No problem – a splash of oxygen peroxide should do the trick

JWC

I was involved in a recently published RCT of a novel wound care system (‘BioxyQuell’), which trailed the application of an aqueous oxygen peroxide (AOP, aka aqueous ozone) lavage on venous leg ulcers. The study isn’t perfect, but the results are encouraging and should serve as a basis for further evaluations.

The RCT was performed in the community setting. Sixty-one patients were enrolled if they had chronic venous leg ulcers, and randomised to either 6 AOP treatments or sham placebo treatments with sterile water over 2 weeks. AOP and placebo arms were both treated with standard-of-care compression bandaging between treatments and for the duration of the study. Patients who completed the initial 8 week RCT were enrolled into a follow-up study evaluating wound healing at 12 weeks, 6 and 12 months. The key results are:

  • No significant difference in wound healing at 8 weeks (the primary outcome). But, something surprising happened during the follow-up study: every single one of the AOP treated patients had healed by 12 months vs. 50% in the placebo arm (Figure 1). Could it really be that a 2 week AOP treatment period has such a remarkable impact on long-term wound healing? It’s just about plausible if there was some pretty fundamental change to the wound bed. But I’d need to see some more data to be convinced!
  • Almost 50% of patients in the placebo arm were healed by 8 weeks. The inclusion criteria required a chronic leg ulcer more than 3 months old, so why did 50% of placebo patients heal? I suspect the answer lies in good compression bandaging, which was mandated during the trial. There’s a temptation to apply the bandages too loosely to be effective to improve patient comfort.
  • AOP patients were significantly less likely to be withdrawn from the study due to wound infection during the first 4 weeks of the RCT (Figure 2). This stark difference makes sense: AOP is a biocide with the capacity to dismantle biofilms, which are involved in wound infection.
  • Pain and bacterial contamination were significantly lower in the AOP arm during the treatment phase. Wound size was also significantly reduced in the AOP arm when accounting for patients with deteriorating infected wounds.

Figure 1: Wound healing in the AOP and placebo arm during the RCT (up to 8 weeks) and follow-up study (up to 12 months).

BxQ healing

Figure 2: Patient withdrawals due to wound infection during the first 8 weeks of the RCT.

BxQ withdrawal

As ever, the study raises as many if not more questions than it answers:

  • What is the optimal treatment regimen for AOP? Is two weeks enough? Is three treatments per week about right (and feasible)? Put another way, how would this study have looked if the AOP treatment was performed for 4 weeks instead of 2? The fact that improvements in wound size reduction, pain, bacterial contamination and withdrawal due to wound infection trailed off after the 2 week treatment period indicates that a longer treatment period should be explored.
  • What is the best application of AOP in healthcare? Acute care? Primary care? Trauma? Diabetic foot?
  • Is ‘wound healing’ the right outcome measure? Perhaps prevention of withdrawals due to wound infection is the most important finding of this study. And don’t underestimate the value of the reduced pain in the AOP arm – the ulcers are very painful and make sufferers pretty miserable!

This was a fair sized randomised, sham placebo controlled, double blinded study performed with tight inclusion and exclusion criteria in the community setting. This sort of RCT is surprisingly rare in the wound care literature. However, it was terminated early (due to lack of significant difference in wound healing and the fact that it took years to recruit a decent number of patients) and the primary outcome (wound healing at 8 weeks) was non-significant. Nonetheless, wound size, pain and bacterial contamination were reduced by AOP treatment, the long-term reductions in wound healing are tantalizing, and reduced withdrawals due to wound infection are tangible.

Article citation: O’Halloran PD, Winter PK, Otter JA, Adams NM, Chewins J. Aqueous oxygen peroxide treatment of VLUs in a primary care-based randomised, doubleblind, placebo-controlled trial. J Wound Care 2014;23:176-90.

Post script: in memoriam

The statistician who formulated and executed the statistical analysis for this study, Carla White, sadly died (too young) during the latter stages of getting this article published. I am sorry not to have the opportunity to work with her again.

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5 thoughts on “Chronic wound? No problem – a splash of oxygen peroxide should do the trick

  1. Thank you for another informative contribution, Jon. I like the concept of going back to the basics but looking at things in a much wider perspective. Along with education, re-education and unlearning old beliefs and practices, reintroducing H2O2 in wound care is a great start for promising outcomes.

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    • Thanks Ameurfina for your comment here. This study evaluated aqueous oxygen peroxide (AOP, aka ozone), not hydrogen peroxide. It would be interesting to see how AOP would compare with 3% hydrogen peroxide, which is also used for topical wound treatment. I note you’re based in Saudi Arabia – what is usually used for the treatment of venous leg ulcers there? Compression bandaging only? Soaking? Lavage? All of the above?

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  2. Thank you Jon,
    I think that the leap to H2O2 was a natural one in that most of us hear the word peroxide and we think of that. After re-reading your post I see you are speaking about O3(aq). Coming from a nursing perspective, I was initially surprised. Application of hydrogen peroxide used to be en vogue with wound care and has since fallen out of use. From what I read of the article use of Aqueous Ozone is not surprising as it accomplishes several factors that affect wound care. One factor is maintaining a moist wound bed. A second factor is to break up biofilms allowing the body to create conditions for cell proliferation and the third factor associated with that is to increase oxygenation of the wound bed. I have read about the applications of ozone generation to purify water supplies and in cleaning the air with the caveats of minimizing direct exposure to humans. Creating an aqueous form would minimize the effects that gaseous ozone would while using those same properties to cleanse wound beds.
    I found this article interesting and I agree that replication of this experiment for a longer duration of treatment would be useful. I would also like to see dosage-related studies as higher concentrations of ozone could cause more tissue damage than lower doses. Balancing bacterial damage over damage of the patient’s own cells.
    Thank you for introducing us to this topic and its potential for wound care.

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    • No, I don’t think so. O3 (Aq) is unstable and would breakdown quickly when applied to surfaces (this is part of the reason why it is safe to use for wounds). You’d be better off using bleach or a hydrogen peroxide based liquid disinfectant, or hydrogen peroxide vapour.

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