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

NCT ID: NCT02326337

Last Updated: 2025-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2018-10-25

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.

Detailed Description

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.

Conditions

Diabetic Foot Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Topical Wound Oxygen 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 Advanced Moist Wound Therapy (AMWT) dressings.

Other Names:

• Topical Wound Oxygen Therapy
• TWO2

Group Type: ACTIVE_COMPARATOR

TWO2 Device

Intervention Type: 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.

Placebo 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.

Group Type: PLACEBO_COMPARATOR

Placebo Device

Intervention Type: 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.

Interventions

TWO2 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.

Intervention Type: DEVICE

Placebo 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.

Intervention Type: DEVICE

Other Intervention Names

TWO2 Therapy; Sham Device, Control Device

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AOTI Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert G Frykberg, DPM

Role: PRINCIPAL_INVESTIGATOR

Carl T. Hayden VA Medical Center

Locations

Carl T. Hayden VA Medical Center

Phoenix, Arizona, United States

NorthBay Center for Wounds

Vacaville, California, United States

Washington DC VA Medical Center

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

The Research Center Inc.

Hialeah, Florida, United States

Advanced Research Institute of Miami

Miami, Florida, United States

Advanced Research Institute of Miami

Miami, Florida, United States

Edward Hines, Jr. VA Hospital

Chicago, Illinois, United States

Advanced Foot & Ankle Center

Las Vegas, Nevada, United States

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Salem VA Medical Center

Salem, Virginia, United States

Avicenne Hospital

Bobigny, , France

Hospital Simone Veil

Eaubonne, , France

Montpellier University Hospital

Montpellier, , France

Städtisches Klinikum Dessau

Dessau, , Germany

Kirchberg Hospital

Luxembourg, , Luxembourg

Northwick Park Hospital

Harrow, , United Kingdom

King's College Hospital

London, , United Kingdom

Countries

United States; France; Germany; Luxembourg; United Kingdom

References

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.

Reference Type: RESULT

PMID: 31619393 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AOTI- TWO2DFU-01

Identifier Type: -

Identifier Source: org_study_id