A Phase 4 interventional study of Topical Wound Oxygen Therapy and Sham Control Topical Wound Oxygen in Venous Leg Ulcer (VLU), sponsored by AOTI Ltd.. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-19.
Sponsored by AOTI Ltd. · Phase 4, Interventional, and Treatment
The purpose of this study is to evaluate the efficacy, safety and economic benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the treatment of venous leg ulcers. Participants will utilize standard of care (SOC) multilayer compression dressings with an inactive wound contact layer. Following a 2-week run-in period with SOC and after meeting all eligibility criteria, subjects will be randomized in a 1:1 ratio with TWO2 therapy or sham control therapy plus SOC. Participants will enter the intervention period of up to 16-weeks, followed by a long-term follow-up period of 52 weeks post randomization.
The full effect of Venous leg ulcers (VLU) on society is poorly understood. While chronic VLU are not considered to have a significant impact on mortality, the burden on patients, caregivers, healthcare systems and related economies cannot be underestimated. VLU affects 2% of the world's population, with 60% progressing to chronic wounds. (1) The reported range of VLU incidence is 0.12 - 1.69% and with a prevalence 0.3 - 1.33%. (2; 3) VLUs are a result of chronic venous insufficiency (CVI) and found to be more prevalent in females than males, with both primary (genetic) and secondary causes that result in valvular incompetence that is further exacerbated by obesity and immobility. (4) With the projected growth of aging and increasingly obese and unhealthy societies, both in the developed and developing world, the anticipated incidence of VLU is expected to rise significantly. (1; 5; 6) It has been well established that the standard of care (SOC) for VLU is the application of conventional compression dressing (CCD), as the successful management of venous hypertension is key to healing VLU. Maintaining a mobile blood flow and delivering oxygen and nutrients to tissues is essential to healing as well as preserving the integrity of skin reducing threat of developing a recurrent VLU.
The role of oxygen in wound healing has been extensively studied. An animal study by Fries et al in 2005 demonstrated that the application of oxygen in partial pressures above those delivered by a well-functioning arterial system, to wounded tissue, resulted in faster healing and more durable tissue. (19) Oxygen is also essential in fighting infection, potentiating the use of antibiotics and upregulating growth factors. (20; 21) A study by Tawfick and Sultan in 2012 demonstrated a significant benefit in healing VLU when both oxygen and cycling compression were employed simultaneously. Utilizing Topical Wound Oxygen (TWO2) therapy™, TWO2 was demonstrated to be superior to SOC, 76% vs 46% healing at 12 weeks (n = 30/65; P \< .0001), with low recurrence rates for patients followed up to three years, 6% vs 47%. Further noteworthy results from this study were the reduction of pain, 8 to 3 in 13 days (on a numerical rating scale) and subjects whose wounds were infected with MRSA demonstrated elimination 46% vs 0% at week 5 (P \<.001). (22)
All subjects will use the TWO2/Sham device for a minimum of 120 minutes a day in their home (where the infrastructure supports remote therapy), 5 times a week for the treatment phase of up to 16 weeks. Monitoring of the wound will take place with bi-weekly clinic visits to assess safety, compliance, wound progression/deterioration, wound photographs and measurements.
The maximum duration for participation in the trial is 52 weeks (+/- 2 weeks). During the follow-up phase, subjects will receive standard care according to the clinician's recommendation and will be asked not to participate in another wound care trial during this period.
369 studies on the registry are indexed under Varicose Ulcer; 77 are open to participants now.
This study's planned enrollment of 212 is above the median of 60 across 309 interventional studies indexed under Varicose Ulcer.
Browse Varicose Ulcer studies →AOTI Ltd. is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Known allergy to any of the protocol-stipulated treatments, or non-tolerance of multilayer, multicomponent compression therapy
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Device: Topical Wound Oxygen Therapy
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.
Device: Sham Control Topical Wound Oxygen
The active intervention is the application of the Topical Wound Oxygen device that supplies cyclical oxygen pressure directly to the wound site within a sealed environment.
The sham control intervention is the application of Topical Wound Oxygen device that supplies topical room air to the wound site within a sealed environment.
Incidence of complete wound closure within 16 weeks with the use of Topical Wound Oxygen Therapy (TWO2)
Percentage incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
Time frame: From Baseline to16 weeks
Percentage Area Reduction (PAR)
Change in wound area will be documented bi-weekly by the use of digital photography and wound mapping
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days)
Incidence of complete wound closure at 12 weeks
Incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
Time frame: From Baseline to12 weeks
Incidence of complete wound closure at 52 weeks
Incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
Time frame: From week 16 to 52 weeks
Time to complete wound closure
Healing difference over Time will be assessed over a 16-week period
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days), 20, 26, 52 weeks (± 2 weeks)
Pain Visual Analog Scale (VAS) score
Pain scores documented on a weekly basis measured using a 0-10 Visual Analog Scale (VAS) score, with zero (0) indicating no pain and 10 indicating the worst possible pain.
Time frame: Baseline weekly up to 16 weeks (±2 days)
Incidence of recurrence
Wounds documented as "healed" will be followed for incidence of recurrence. Count of wound recurrences of healed wounds. For healed wounds, VLU recurrence was collected via phone calls and subjects at follow up timelines.
Time frame: From Baseline up to week 16, week 20, 26 (± 1 week), 52 (± 2 weeks)
Incidence of Adverse Events at 16 weeks
Total number of different types of adverse events in participants who reported with any untoward medical event
Time frame: From Baseline to16 weeks
Incidence of Serious Adverse Events at 16 weeks
Total number of different types of serious adverse events in participants who reported that: * results in death * is life-threatening (places the subject at immediate risk of death from the experience as it occurred) * results in a persistent or significant disability/incapacity (substantial disruption of one's ability to carry out normal life functions) * results in medical or surgical intervention * results in or prolongs an existing hospitalization (even if the hospitalization is a precautionary measure for observation)
Time frame: From Baseline to16 weeks
Incidence of Serious Adverse Events at 52 weeks
Total number of different types of serious adverse events in participants who reported that: * results in death * is life-threatening (places the subject at immediate risk of death from the experience as it occurred) * results in a persistent or significant disability/incapacity (substantial disruption of one's ability to carry out normal life functions) * results in medical or surgical intervention * results in or prolongs an existing hospitalization (even if the hospitalization is a precautionary measure for observation)
Time frame: From 16 to 52 weeks
Change in Venous Clinical Severity Score (VCSS)
Mean change in Venous Clinical Severity Score (VCSS) from baseline to week 16. VCSS assesses nine common signs/symptoms of venous disease and each item is scored individually with a minimum score of "0" and maximum score of "3". The individual items are added together to assess change from baseline. Higher scores mean worst outcome.
Time frame: From Baseline to 16 weeks
Elimination of Infection
Wound cultures will be taken at the Baseline visit then again at week 6. Wounds defined as "infected" at the baseline visit and "not infection" at weeks 6, are documented as wound infection elimination.
Time frame: From Baseline to week 6
Change in Health-related Quality of Life (Venous Leg Ulcer Quality of life Questionnaire ~ (VLU-QoL-34))
Mean difference in change in Venous Leg Ulcer Quality of life Questionnaire \~ (VLU-QoL-34) from baseline to 16 weeks. Crude subscale scores for each group are not shown (each crude subscale is scored 1 to 5 at baseline and 16 weeks); higher mean differences in change from baseline to 16 weeks within groups indicate greater change on the subscales for that group.
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Emotional distress
The emotional distress will be assessed through the total score of the Hospital Anxiety and Depression Scale, comprising both anxiety and depression scales (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 42, with higher results indicating higher levels of distress.
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Anxiety symptoms
The anxious symptomatology will be assessed through the Hospital Anxiety and Depression Scale (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 21, with higher results indicating higher levels of anxiety symptoms.
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Depression
The depressive symptomatology will be assessed through the Hospital Anxiety and Depression Scale (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 21, with higher results indicating higher levels of depression symptoms.
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Change in Health-related Quality of Life (EuroQol-5D 3L)
Mean difference in change measured by EuroQol 5D (EQ5D 3L) from baseline to 16 weeks. Crude health state scores for each group are not shown (health state is scored 0 to 100 at baseline and 16 weeks); higher mean differences in change from baseline to 16 weeks within groups indicate greater change on health state for that group.
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.