Efficacy, Safety and Economic Benefits of Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multi-national, Multi-center, Prospective, Randomized, Double Blinded, Placebo-controlled Trial to Evaluate the Efficacy of HyperBox Cyclical Topical Wound Oxygen Therapy (TWO2) in the Treatment of Chronic Diabetic Foot Ulcers

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Device: TWO2 Device
* Device: Placebo Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a documented diagnosis of Diabetes mellitus Type 1 or 2 Foot ulcer at or below ankle with duration of more than 4 weeks but no longer than 1 year If the index ulcer is a post amputation wound date of surgery must be > 30 days 2 week run in period with less than 30% wound size reduction University of Texas Grade 1A, 1B, 1C, 1D, 2A, 2B, 2C, or 2D (Appendix I) Ulcer is ≥ 1cm2 and ≤ 20cm2 after debridement at start of run-in period If more than one ulcer is present on the foot, only the largest is considered in the study (Index ulcer) Index ulcer must be ≥ 1cm away from any other ulcers present on the foot Adequate perfusion with ABI > 0.7 And TcpO2 > 30mmHg OR skin perfusion > 30mmHG OR Toe pressure > 30mmHg OR Duplex with biphasic waveforms below the knee No planned revascularization procedure or vascular surgery within the last/next 30 days Subject and/or caregiver are willing and able to comply with all specified care and visit requirements Subject has a reasonable expectation of completing the study; according to the Investigator's clinical judgment Exclusion Criteria: Evidence of gangrene on any part of affected limb Documented evidence of osteomyelitis on any part of affected limb Index ulcer has exposed bone Index ulcer exhibits signs of severe clinical infection that requires hospitalization or immediate surgical intervention Active Charcot foot on the study limb Subject participated in another investigational device, drug or biological trial within last 30 days Uncontrolled diabetes: HbA1c > 12 % Renal dialysis or creatinine > 2.5 Known immune insufficiency Chronic steroid use or immunosuppressive agents within the last three (3) months or is anticipated to require them during the course of the study Active treatment for malignancy (not specific to study limb) Patient has a Deep Vein Thrombosis within the last 30 days Subject has received growth factor therapy (e.g., autologous platelet-rich plasma gel, becaplermin, bilayered cell therapy, dermal substitute, extracellular matrix) within the screening period Subject may not be pregnant at the time of treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group Sequential Design of a maximum of 220 subjects with two predetermined interim analyses at 73 and 146 subjects
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topical Wound Oxygen Device<br>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<br>* 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.<br>* Other names: TWO2 Therapy;|
| Placebo Comparator: Placebo Device<br>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<br>* 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.<br>* Other names: Sham Device, Control Device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound closure within 12 weeks with the use of Topical Wound Oxygen Therapy (TWO2) | Incidence of complete wound closure defined as 100% skin re-epithelialization without dressing requirements which is confirmed by 2 consecutive study visits 2 weeks apart. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete wound closure | Wounds not closed at the end of the12 week treatment phase are assessed for 100% skin re-epithelialization without dressing requirements at a study visit or by telephone call and review of medical record after a further 12 and 26 weeks . | 54 weeks | 
| Change in wound size over time | Wound size will be documented at study visits by the use of digital photography and wound-mapping software. | 54 weeks | 
| Incidence of recurrence | Wounds that are documented as closed will be assessed for recurrence at a study visit or by telephone call and review of medical records at 12 and 26 weeks after the treatment phase. | 54 weeks | 
| Incidence of amputation | Incidence of amputation will be documented throughout the study | 54 weeks | 
| Incidence of adverse device effects | Incidence of adverse device effects will be documented throughout the study | 54 weeks | 
| Quality of Life Assessment | Quality of Life is a composite outcome measure assessed by the use of a Visual Analogue Scale to document level of pain and the Cardiff Wound Impact Schedule questionnaire. | 54 weeks | 
| Economic Analysis | 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 and 12 and 26 weeks post treatment. | 54 weeks |