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Efficacy, Safety and Economic Benefits of Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers (TWO2DFU)

Primary Purpose

Diabetic Foot Ulcer

Status
Unknown status
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
TWO2 Device
Placebo Device
Sponsored by
AOTI Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Foot Ulcer

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Carl T. Hayden VA Medical Center
  • NorthBay Center for Wounds
  • Washington DC VA Medical Center
  • The Research Center Inc.
  • Advanced Research Institute of Miami
  • Advanced Research Institute of Miami
  • Edward Hines, Jr. VA Hospital
  • Advanced Foot & Ankle Center
  • Hunter Holmes McGuire VA Medical Center
  • Salem VA Medical Center
  • Avicenne Hospital
  • Hospital Simone Veil
  • Montpellier University Hospital
  • Städtisches Klinikum Dessau
  • Kirchberg Hospital
  • Northwick Park Hospital
  • King's College Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Topical Wound Oxygen Device

Placebo Device

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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 .
Change in wound size over time
Wound size will be documented at study visits by the use of digital photography and wound-mapping software.
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.
Incidence of amputation
Incidence of amputation will be documented throughout the study
Incidence of adverse device effects
Incidence of adverse device effects will be documented throughout the study
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.
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.

Full Information

First Posted
November 19, 2014
Last Updated
February 19, 2018
Sponsor
AOTI Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02326337
Brief Title
Efficacy, Safety and Economic Benefits of Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers
Acronym
TWO2DFU
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 2014 (undefined)
Primary Completion Date
February 5, 2018 (Actual)
Study Completion Date
December 15, 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AOTI Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Foot Ulcer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Group Sequential Design of a maximum of 220 subjects with two predetermined interim analyses at 73 and 146 subjects
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Topical Wound Oxygen Device
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo Device
Arm Type
Placebo Comparator
Arm Description
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
Intervention Name(s)
TWO2 Device
Other Intervention Name(s)
TWO2 Therapy
Intervention Description
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
Intervention Name(s)
Placebo Device
Other Intervention Name(s)
Sham Device, Control Device
Intervention Description
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.
Primary Outcome Measure Information:
Title
Wound closure within 12 weeks with the use of Topical Wound Oxygen Therapy (TWO2)
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Time to complete wound closure
Description
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 .
Time Frame
54 weeks
Title
Change in wound size over time
Description
Wound size will be documented at study visits by the use of digital photography and wound-mapping software.
Time Frame
54 weeks
Title
Incidence of recurrence
Description
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.
Time Frame
54 weeks
Title
Incidence of amputation
Description
Incidence of amputation will be documented throughout the study
Time Frame
54 weeks
Title
Incidence of adverse device effects
Description
Incidence of adverse device effects will be documented throughout the study
Time Frame
54 weeks
Title
Quality of Life Assessment
Description
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.
Time Frame
54 weeks
Title
Economic Analysis
Description
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.
Time Frame
54 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert G Frykberg, DPM
Organizational Affiliation
Carl T. Hayden VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Carl T. Hayden VA Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
NorthBay Center for Wounds
City
Vacaville
State/Province
California
ZIP/Postal Code
95687
Country
United States
Facility Name
Washington DC VA Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
The Research Center Inc.
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
Advanced Research Institute of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Advanced Research Institute of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33134
Country
United States
Facility Name
Edward Hines, Jr. VA Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60141
Country
United States
Facility Name
Advanced Foot & Ankle Center
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119
Country
United States
Facility Name
Hunter Holmes McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Salem VA Medical Center
City
Salem
State/Province
Virginia
ZIP/Postal Code
24153
Country
United States
Facility Name
Avicenne Hospital
City
Bobigny
ZIP/Postal Code
93000
Country
France
Facility Name
Hospital Simone Veil
City
Eaubonne
ZIP/Postal Code
95600
Country
France
Facility Name
Montpellier University Hospital
City
Montpellier
ZIP/Postal Code
34000
Country
France
Facility Name
Städtisches Klinikum Dessau
City
Dessau
ZIP/Postal Code
06847
Country
Germany
Facility Name
Kirchberg Hospital
City
Luxembourg
ZIP/Postal Code
L-2540
Country
Luxembourg
Facility Name
Northwick Park Hospital
City
Harrow
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31619393
Citation
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.
Results Reference
derived

Learn more about this trial

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

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