An interventional study of TWO2 Device and Placebo Device in Diabetic Foot Ulcer, sponsored by AOTI Ltd.. Completed at 17 sites in 5 countries. Open to participants aged 18 Years to 89 Years. Per ClinicalTrials.gov, last updated 2025-10-27.
Sponsored by AOTI Ltd. · Not applicable, Interventional, and Treatment
The purpose of this study is to evaluate the efficacy, safety and economical benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the treatment of chronic diabetic foot ulcers. Subjects will wear a standardized off-loading device and use advanced moist wound therapy (AMWT) dressings. Following a 2 week run-in period with the standardized care and after meeting all the eligibility criteria, half the subjects will use the TWO2 device, while the other half will use a sham device.
Subjects meeting the initial eligibility criteria will enter a 2 week run-in period with a standardized off-loading device, advanced moist wound therapy (AMWT) dressings and will receive sharp debridement. Subjects with wounds that do not decrease more than 30% at the end of the 2 week run-in period and where all other eligibility criteria are met, will be randomized to either the TWO2 device arm, or sham (placebo) device arm.
All subjects will use the TWO2/Sham device for 90 minutes a day at their home or nursing care facility 5 times a week for the treatment phase of up to 12 weeks. Monitoring of the wound will take place with weekly clinic visits for safety and compliance assessment and documentation. Weekly wound photographs and measurements will be taken. Wounds that close at, or before, 12 weeks will continue to use TWO2/sham device, off-loading and AMWT and have an additional visit two weeks later to confirm wound closure. All subjects whether healed or not will enter a follow up period of an additional 12 and 38 weeks.
The maximum duration for participation in the trial is 54 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.
1,077 studies on the registry are indexed under Diabetic Foot; 222 are open to participants now.
This study's enrollment of 73 is above the median of 60 across 847 interventional studies indexed under Diabetic Foot.
Browse Diabetic Foot studies →AOTI Ltd. is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
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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:
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.
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.
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.
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.
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.
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.
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.
Application of the Topical Wound Oxygen (TWO2) device that supplies cyclical oxygen pressure directly to the wound site within a sealed and humidified environment for 90 minutes, 5 times a week with Advanced Moist Wound Therapy (AMWT) dressings. Other Names: * Topical Wound Oxygen Therapy * TWO2
Device: TWO2 Device
Application of placebo device that does not supply cyclical oxygen pressure directly to the wound site within a sealed and humidified environment for 90 minutes, 5 times a week with AMWT dressings.
Device: Placebo Device
Application of the Topical Wound Oxygen (TWO2) device that supplies cyclical oxygen pressure directly to the wound site within a sealed and humidified environment for 90 minutes, 5 times a week with AMWT dressings.
Also known as: TWO2 Therapy
Application of placebo device that does not supply cyclical oxygen pressure directly to the wound site within a sealed and humidified environment for 90 minutes, 5 times a week with AMWT dressings.
Also known as: Sham Device, Control Device
Wound Closure Within 12 Weeks With the Use of Topical Wound Oxygen Therapy (TWO2)
Number of Participants with complete wound closure defined as 100% skin re-epithelialization without dressing requirements which is confirmed by 2 consecutive study visits 2 weeks apart.
Time frame: 12 weeks
Absolute Change in Ulcer Area
Absolute change in ulcer area over 12 weeks in cm2
Time frame: 12 weeks
Ulcer Recurrence
Number of diabetic foot ulcers with recurrence at 12 months
Time frame: 12 months
Number of Amputation Events
Number of amputation events during interventional period of the study.
Time frame: 12 weeks
Incidence of Adverse Events
Incidence of serious adverse events and adverse events
Time frame: 54 weeks
Quality of Life Assessment
The Cardiff Wound Impact Schedule questionnaire to measure quality of life. Measure of well-being items from each scale are summated, physical symptoms, everyday living and social life. The items are rated for the extent of the experience and each item is given a number value. This allows the patients to weight the items included in the scale. The well-being scale is scored on a 5-point Likert scale, with response options from 'strongly agree' to 'strongly disagree'. All three scales are then transformed onto a minimum = 0 up to a maximum = 100, where a low score indicates worse, and a high score indicates better feeling of well-being.
Time frame: 12 weeks
Economic Analysis
Not performed or reported. Economic Analysis is a composite measure of the wound before the study (up to one year) and for the duration of the study. The assessment is obtained by documenting treatment history of the wound that includes types of dressings used, time taken for dressing changes, by whom dressings are changed, and type and duration of hospitalization as well as the administration of the EQ-5D questionnaire at the Baseline visit, weeks 4, 8 and 12 on treatment.
Time frame: 12 weeks
Time to Complete Wound Closure in Weeks
Time to 100% wound closure utilizing Cox proportional hazards model, a statistical measure of difference of time to event (healing). Subjects who withdraw from treatment will be entered into the analysis and censored at the time they withdraw from the trial or are lost to follow up. The analysis will consider covariates that might influence the outcome in the trial.
Time frame: 12 weeks or wound closure
| Milestone | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| Started | 36 | 37 |
| Completed | 36 | 37 |
| Not completed | 0 | 0 |
Number of Participants with complete wound closure defined as 100% skin re-epithelialization without dressing requirements which is confirmed by 2 consecutive study visits 2 weeks apart.
| Participants | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| Wound Closure Within 12 Weeks With the Use of Topical Wound Oxygen Therapy (TWO2) | 15 | 5 |
Absolute change in ulcer area over 12 weeks in cm2
| cm2 | Topical Wound Oxygen Device | Placebo |
|---|---|---|
| Absolute Change in Ulcer Area | 1.97 ± 2.12 | .4 ± 0.041 |
Number of diabetic foot ulcers with recurrence at 12 months
| Count of wounds with recurrence | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| Ulcer Recurrence | 1 | 2 |
Number of amputation events during interventional period of the study.
| Count of events | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| Number of Amputation Events | 2 | 3 |
Incidence of serious adverse events and adverse events
| Count of events | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| Serious Adverse Events | 10 | 10 |
| Adverse Events | 8 | 8 |
| Device related death | 0 | 0 |
The Cardiff Wound Impact Schedule questionnaire to measure quality of life. Measure of well-being items from each scale are summated, physical symptoms, everyday living and social life. The items are rated for the extent of the experience and each item is given a number value. This allows the patients to weight the items included in the scale. The well-being scale is scored on a 5-point Likert scale, with response options from 'strongly agree' to 'strongly disagree'. All three scales are then transformed onto a minimum = 0 up to a maximum = 100, where a low score indicates worse, and a high score indicates better feeling of well-being.
| units on a scale | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| Quality of Life Assessment | 9.1 ± 13.9 | 0.1 ± 16.9 |
Not performed or reported. Economic Analysis is a composite measure of the wound before the study (up to one year) and for the duration of the study. The assessment is obtained by documenting treatment history of the wound that includes types of dressings used, time taken for dressing changes, by whom dressings are changed, and type and duration of hospitalization as well as the administration of the EQ-5D questionnaire at the Baseline visit, weeks 4, 8 and 12 on treatment.
No measurements were reported for this outcome.
Time to 100% wound closure utilizing Cox proportional hazards model, a statistical measure of difference of time to event (healing). Subjects who withdraw from treatment will be entered into the analysis and censored at the time they withdraw from the trial or are lost to follow up. The analysis will consider covariates that might influence the outcome in the trial.
| Weeks | Topical Wound Oxygen Device | Placebo |
|---|---|---|
| Time to Complete Wound Closure in Weeks | 8.2 ± 1.9 | 6.3 ± 4.2 |
Collected over 54 Weeks (baseline up to maximum duration of study participation).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Topical Wound Oxygen Device | 2/36 (5.6%) | 6/36 (16.7%) | 6/36 (16.7%) |
| Placebo Device | 2/37 (5.4%) | 7/37 (18.9%) | 7/37 (18.9%) |
| Event | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| OsteomyelitisMusculoskeletal and connective tissue disorders | 2/36 | 5/37 |
| Wound InfectionSkin and subcutaneous tissue disorders | 3/36 | 2/37 |
| Urinary Tract InfectionRenal and urinary disorders | 2/36 | 0/37 |
| Cardiovascular EventCardiac disorders | 1/36 | 0/37 |
| UTC Grade II UlcerationSkin and subcutaneous tissue disorders | 1/36 | 0/37 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 1/36 | 0/37 |
| Hyperglycemic eventEndocrine disorders | 0/36 | 1/37 |
| Necrotic TissueSkin and subcutaneous tissue disorders | 0/36 | 1/37 |
| Severe MacerationSkin and subcutaneous tissue disorders | 0/36 | 1/37 |
| Event | Topical Wound Oxygen Device | Placebo Device |
|---|---|---|
| UTC Grade I UlcerSkin and subcutaneous tissue disorders | 3/36 | 0/37 |
| Ulcer DeclineSkin and subcutaneous tissue disorders | 2/36 | 0/37 |
| MacerationSkin and subcutaneous tissue disorders | 0/36 | 2/37 |
| Minor InfectionSkin and subcutaneous tissue disorders | 1/36 | 1/37 |
| Minor OsteomyelitisMusculoskeletal and connective tissue disorders | 1/36 | 0/37 |
| EdemaVascular disorders | 1/36 | 1/37 |
| Minor Necrotic TissueMusculoskeletal and connective tissue disorders | 0/36 | 1/37 |
| CellulitisSkin and subcutaneous tissue disorders | 0/36 | 1/37 |
| DeramatitisSkin and subcutaneous tissue disorders | 0/36 | 1/37 |
| ContusionSkin and subcutaneous tissue disorders | 0/36 | 1/37 |
| Age, Continuous(years) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Mean | 64.6 ± 10.3 | 61.9 ± 9.5 | 63.3 ± 9.9 |
| Sex: Female, Male(Participants) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Female | 4 | 6 | 10 |
| Male | 32 | 31 | 63 |
| Race/Ethnicity, Customized(Participants) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| White/Hispanic | 26 | 24 | 50 |
| Black | 5 | 5 | 10 |
| Asian | 2 | 1 | 3 |
| American Indian | 0 | 1 | 1 |
| Not reported | 3 | 6 | 9 |
| Diabetes Type 2(Participants) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Count of participants | 32 | 33 | 65 |
| BMI(Kg/m^2) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Mean | 30.8 ± 5.9 | 31.2 ± 7.6 | 31 ± 6.8 |
| Wound area (cm2)(cm^2) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Mean | 3.02 ± 2.66 | 3.22 ± 2.54 | 3.13 ± 2.57 |
| Wound perimeter (cm)(cm) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Mean | 6.22 ± 2.85 | 6.85 ± 4.18 | 6.54 ± 3.55 |
| Ulcer duration (days)(Days) | Topical Wound Oxygen Device | Placebo Device | Total |
|---|---|---|---|
| Mean | 160.3 ± 96 | 174.6 ± 94 | 166.4 ± 95 |
6 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Oct 2014 to primary completion in Feb 2018, 40 months.
Results were first posted in Apr 2025, 7 years 2 months after primary completion.
Of 103 industry-sponsored interventional studies with no phase under Diabetic Foot, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 40. This study's 40 months is above that.
Counting every sponsor, half of 343 studies reached it within 22 months; a quarter within 9 and three quarters within 39.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2025. You cannot join it, but the record below documents what was studied.
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