Topical Wound Oxygen Therapy for Leg Ulcers

(VaLUe I Trial)

Overseen By Despina Herodotou, MRCPod, DABPMi

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: AOTI Ltd.

Must not be taking: Systemic steroids, Immunosuppressive agents

Disqualifiers: DVT, Surgery, Osteomyelitis, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

212 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness and safety of a new therapy called Topical Wound Oxygen (TWO2) Therapy for treating venous leg ulcers. These ulcers are open sores on the lower legs caused by poor blood flow in the veins. Participants will receive either the TWO2 treatment or a sham (inactive) treatment, along with standard compression dressings, to determine which is more effective. Individuals with a venous leg ulcer below the knee, present for at least six weeks, may be suitable for this trial. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications like systemic steroids over 10mg daily or immunosuppressive agents, these might interfere with the study treatment, so it's best to discuss with the study team.

What is the safety track record for Topical Wound Oxygen Therapy?

Research has shown that Topical Wound Oxygen (TWO2) Therapy is generally easy for patients to manage. In studies involving individuals with difficult-to-heal venous ulcers, the treatment did not cause serious side effects. Observational studies found that 80.95% of wounds healed in the group using TWO2, compared to 37.5% in those receiving only standard care. This suggests the therapy might be both effective and safe. Since this trial is in a late phase, the treatment has been tested in people before and is considered safe enough to continue. It is important to consult healthcare professionals to determine if this treatment is suitable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard care for leg ulcers, which often includes dressings and compression therapy, Topical Wound Oxygen Therapy (TWO2) stands out because it delivers oxygen directly to the wound site. This unique delivery method not only provides oxygen but also utilizes cyclical compression to enhance healing. Researchers are excited about TWO2 because it creates a sealed environment filled with oxygen, which can potentially speed up the healing process by promoting better blood flow and tissue regeneration. This innovative approach could offer a significant advantage over traditional treatments, especially for patients struggling with chronic leg ulcers.

What evidence suggests that Topical Wound Oxygen Therapy is effective for venous leg ulcers?

Research has shown that Topical Wound Oxygen (TWO2) Therapy, which participants in this trial may receive, effectively heals venous leg ulcers. In previous studies, 80.95% of wounds treated with TWO2 healed, compared to only 37.5% with standard care alone. This therapy uses oxygen to help wounds heal faster and more effectively. Additionally, fewer ulcers treated with TWO2 recurred compared to other methods, indicating that TWO2 not only speeds up healing but also reduces the chance of ulcers returning. Participants in this trial may also receive a Sham Control Topical Wound Oxygen device, which does not deliver oxygen, to compare the effectiveness of the active treatment. ^{1 2 3 5 6}

Who Is on the Research Team?

Mike Griffiths, DProf, DMS, CRT, FCMI

Principal Investigator

AOTI Ltd.

Anil Hingorani, MD

Principal Investigator

Wael Tawfick, MB.BCH, MRCSI.

Principal Investigator

University of Galway

Are You a Good Fit for This Trial?

This trial is for individuals with chronic venous leg ulcers who have been using standard multilayer compression dressings. Participants must complete a 2-week period with these dressings before starting the trial and meet all other requirements.

Inclusion Criteria

My wound area totals 50cm2 or less.

My ulcer has been present for 6 weeks to 5 years.

I have a long-lasting leg ulcer below the knee due to vein problems.

Exclusion Criteria

NYHA Class IV

My wound exposes bone, muscle, or tendon.

I had surgery to improve blood flow in my limb within the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Run-in

Participants undergo a run-in period with standard of care (SOC) multilayer compression dressings

2 weeks

Treatment

Participants receive either TWO2 therapy or sham control therapy plus SOC for up to 16 weeks

16 weeks

Bi-weekly clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham Control Topical Wound Oxygen
• Topical Wound Oxygen Therapy

Trial Overview The study tests Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy against a sham control therapy, both in addition to standard care. Patients are randomly assigned to either real or sham treatment for up to 16 weeks, followed by a year of follow-up.

How Is the Trial Designed?

Group I: Topical Wound Oxygen Therapy Device Active Control 1 Intervention

Topical Wound Oxygen (TWO2) device in combination with the extremity chamber delivers oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with oxygen for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer.

Group II: Sham Control Topical Wound Oxygen (TWO2) device Placebo Group 1 Intervention

A Sham Control Topical Wound Oxygen (TWO2) device in combination with the extremity chamber that does not deliver oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with room air for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer.

Who Is Running the Clinical Trial?

AOTI Ltd.

Lead Sponsor

Trials

3

Recruited

310+

Published Research Related to This Trial

Topical oxygen therapy (tOT) was used on 28 patients with peripheral arterial disease (PAD) and non-healing ulcers, showing a 25% complete healing rate and a 66% reduction in wound area, indicating its potential effectiveness as an adjunctive treatment.

tOT is a safer and more convenient alternative to hyperbaric oxygen therapy, with no major limb amputations reported, suggesting it could be a viable option for patients who have undergone revascularization or debridement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive topical oxygen therapy for wound healing in patients with peripheral arterial disease. Vulakh, GM., Hingorani, AP., Ascher, E., et al.[2023]

A small evaluation involving 18 patients with pressure ulcers showed that topical oxygen therapy, using a haemoglobin spray, led to wound healing progression in all cases and significant size reduction in 17 out of 18 wounds.

This therapy is easy to use, requiring no special training, and can be applied in any care setting, highlighting its potential as an effective intervention for managing chronic pressure ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A topical haemoglobin spray for oxygenating pressure ulcers: a pilot study. Tickle, J.[2015]

Topical pressurized oxygen therapy is a non-invasive method that delivers humidified oxygen directly to chronic and hypoxic wounds, supporting their healing process.

The article emphasizes the importance of integrating expert opinions and existing evidence to create consensus statements that guide the use of this therapy in various clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based practice standards for the use of topical pressurised oxygen therapy. Orsted, HL., Poulson, R., Baum, J., et al.[2021]

Topical oxygen therapy is a promising treatment option for difficult-to-heal lower extremity wounds, supported by various in vitro, preclinical, and clinical data.

While randomized controlled trials are still needed, current evidence suggests that it can be used as a second-line therapy for patients with refractory wounds, with specific protocols for administration and patient management provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based recommendations for the use of topical oxygen therapy in the treatment of lower extremity wounds. Gordillo, GM., Sen, CK.[2022]

Topical oxygen therapy (TOT) has been found to significantly improve complete wound healing in patients with Wagner 1 and 2 diabetic foot ulcers, with a risk ratio of 1.59 based on a meta-analysis of four randomized controlled trials involving various patient and wound characteristics.

The evidence supporting TOT as an effective adjunct therapy is considered moderate, indicating it is a viable treatment option for chronic diabetic foot ulcers when there is no infection or ischemia present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Topical Wound Oxygen Therapy in Healing Chronic Diabetic Foot Ulcers: Systematic Review and Meta-Analysis. Carter, MJ., Frykberg, RG., Oropallo, A., et al.[2023]

In a double-blind randomized controlled trial involving patients with chronic diabetic foot ulcers (DFUs), the use of multimodality cyclical pressure Topical Wound Oxygen (TWO2) therapy significantly improved healing rates, achieving a closure rate of 41.7% compared to 13.5% in the sham control group at 12 weeks.

At 12 months, 56% of ulcers in the TWO2 therapy group were closed, compared to only 27% in the control group, indicating that TWO2 therapy is an effective adjunctive treatment for refractory DFUs that have not healed with standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study. Frykberg, RG., Franks, PJ., Edmonds, M., et al.[2021]

In a study of 83 patients with refractory venous ulcers, topical wound oxygen (TWO(2)) treatment resulted in 80% of ulcers completely healing within 12 weeks, compared to only 35% for conventional compression dressings (CCD).

TWO(2) not only accelerated healing time (median of 45 days vs. 182 days for CCD) but also significantly reduced pain and recurrence rates, making it a promising option for managing refractory venous ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does topical wound oxygen (TWO2) offer an improved outcome over conventional compression dressings (CCD) in the management of refractory venous ulcers (RVU)? A parallel observational comparative study. Tawfick, W., Sultan, S.[2016]

In a study involving 32 patients and 58 wounds treated with topical oxygen over 9 months, 38 wounds healed successfully, indicating that topical oxygen therapy can promote wound healing without causing complications.

Topical oxygen therapy offers a safer alternative to systemic hyperbaric oxygen therapy, as it avoids risks of oxygen toxicity and allows for at-home treatment, making it accessible to more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical oxygen as an adjunct to wound healing: a clinical case series. Kalliainen, LK., Gordillo, GM., Schlanger, R., et al.[2022]

In a study of 20 patients with acute traumatic musculoskeletal wounds, low-cost topical oxygen therapy (TOT) significantly reduced wound size from an average of 79.3 cm² to 69.6 cm² after treatment, indicating its efficacy in wound healing.

TOT also improved wound quality, as shown by a decrease in the modified wound infection checklist score from 13.6 to 0.8, with all patients showing no bacterial growth in cultures after treatment, suggesting a positive impact on infection control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical oxygen therapy in acute traumatic musculoskeletal wounds of the foot and ankle. Kamal, S., Sehgal, A., Shahi, P., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11234139/

The efficacy of topical oxygen therapy for wound healing In observational studies, the rate of healed wounds was 37.5% in the standard care group and 80.95% in the adjuvant TOT group, which shows a ...

2. diabetesjournals.org diabetesjournals.org/care/article/43/3/616/35667/A-Multinational-Multicenter-Randomized-Double

A Multinational, Multicenter, Randomized, Double-Blinded ... The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06754735

Trial to Evaluate Cyclical Topical Wound Oxygen Therapy ... The purpose of this study is to evaluate the efficacy, safety and economic benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1078588409002032

Does Topical Wound Oxygen (TWO 2 ) Offer an Improved ... Topical wound oxygen (TWO2) may help wound healing in the management of refractory venous ulcers (RVU). The aim of this study was to measure the effect of ...

5. aotinc.net aotinc.net/wp-content/uploads/2013/12/TWO2-Clinical-Evidence-Overview-Dec-2015.pdf

24-31_OWM0610_Blackman:Layout 1 After 36 months follow-up, 14 of the 30 healed CCD ulcers showed recurrence compared to 3 of the 51 TWO2-healed ulcers. The TWO2 is effective and valuable in ...

6. aotinc.net aotinc.net/wp-content/uploads/2022/01/8-4-Tawfick-TWO2-vs-CCD-2012-1.pdf

Technical and Clinical Outcome of Topical Wound ... The leg ulcer was swabbed for culture and sensitivity. The pain numerical rating scale was used prior to therapy and repeated every 3 days. Ulcers were cleaned, ...