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

NCT02326337 | Completed Results DMC FDA Device

• 1 other identifier: AOTI- TWO2DFU-01
• Study Type: interventional
• Target: 73
• Locations: 5 countries
• Sites: 17

Brief Summary

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.

Conditions

Diabetic Foot Ulcer

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks

Secondary Outcomes (7)

• Absolute Change in Ulcer Area

  12 weeks

• Ulcer Recurrence

  12 months

• Number of Amputation Events

  12 weeks

• Incidence of Adverse Events

  54 weeks

• Quality of Life Assessment

  12 weeks

Study Arms (2)

Topical Wound Oxygen Device

ACTIVE COMPARATOR

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

Placebo Device

PLACEBO COMPARATOR

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

Interventions

TWO2 Device 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

Topical Wound Oxygen Device

Placebo Device 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.

Also known as: Sham Device, Control Device

Placebo Device

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AOTI Ltd.: lead

Study Sites (17)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 85012, United States

Location

NorthBay Center for Wounds

Vacaville, California, 95687, United States

Location

Washington DC VA Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

The Research Center Inc.

Hialeah, Florida, 33013, United States

Location

Advanced Research Institute of Miami

Miami, Florida, 33012, United States

Location

Advanced Research Institute of Miami

Miami, Florida, 33134, United States

Location

Edward Hines, Jr. VA Hospital

Chicago, Illinois, 60141, United States

Location

Advanced Foot & Ankle Center

Las Vegas, Nevada, 89119, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Salem VA Medical Center

Salem, Virginia, 24153, United States

Location

Avicenne Hospital

Bobigny, 93000, France

Location

Hospital Simone Veil

Eaubonne, 95600, France

Location

Montpellier University Hospital

Montpellier, 34000, France

Location

Städtisches Klinikum Dessau

Dessau, 06847, Germany

Location

Kirchberg Hospital

Luxembourg, L-2540, Luxembourg

Location

Northwick Park Hospital

Harrow, HA1 3UJ, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Frykberg RG, Franks PJ, Edmonds M, Brantley JN, Teot L, Wild T, Garoufalis MG, Lee AM, Thompson JA, Reach G, Dove CR, Lachgar K, Grotemeyer D, Renton SC; TWO2 Study Group. 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. Diabetes Care. 2020 Mar;43(3):616-624. doi: 10.2337/dc19-0476. Epub 2019 Oct 16.

  PMID: 31619393 RESULT

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Results Point of Contact

• Title: Dr. Mike Griffiths (Medical Director)
• Organization: AOTI Ltd.

mike.griffiths@aotinc.net

+1(760) 431 4700

Study Officials

• Robert G Frykberg, DPM

  Carl T. Hayden VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Group Sequential Design of a maximum of 220 subjects with two predetermined interim analyses at 73 and 146 subjects

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: December 29, 2014
• Study Start: October 1, 2014
• Primary Completion: February 5, 2018
• Study Completion: October 25, 2018
• Last Updated: October 27, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-10

Locations

GB (2); LU (1); US (10); FR (3); DE (1)