Efficacy, Safety and Economic Benefits of Topical Wound O... | NCT02326337

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Absolute Change in Ulcer Area	Absolute change in ulcer area over 12 weeks in cm2	12 weeks
Ulcer Recurrence	Number of diabetic foot ulcers with recurrence at 12 months

Eligibility Module

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

Name	Affiliation	Role
Robert G Frykberg, DPM	Carl T. Hayden VA Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Carl T. Hayden VA Medical Center		Phoenix	Arizona	85012	United States
NorthBay Center for Wounds

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31619393	Result	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 Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Sep 24, 2016

Arm/Group Information

ID	Title	Description
BG000	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 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.
BG001	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. 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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00036 BG00137 BG00273

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00064.6± 10.3 BG00161.9± 9.5 BG00263.3± 9.9

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG0016 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White/Hispanic

Title	Measurements
	BG00026 BG00124 BG002

Diabetes Type 2

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00032 BG00133 BG002

BMI

Mean

Standard Deviation

Kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00030.8± 5.9 BG00131.2± 7.6 BG002

Wound area (cm2)

Mean

Standard Deviation

cm^2

Title

Denominators

Categories

Title	Measurements
	BG0003.02± 2.66 BG0013.22± 2.54 BG002

Wound perimeter (cm)

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG0006.22± 2.85 BG0016.85± 4.18 BG002

Ulcer duration (days)

Mean

Standard Deviation

Days

Title

Denominators

Categories

Title	Measurements
	BG000160.3± 96 BG001174.6± 94 BG002

The University of Texas Staging System for Diabetic Foot Ulcers Grade I

Grade IA: Superficial ulcer, not involving tendon capsule or bone Grade IB: With Infection Grade IC: With ischemia Grade ID: With infection and ischemia

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00022 BG001

The University of Texas Staging System for Diabetic Foot Ulcers Grade II

Grade IIA: Ulcer penetrating to tendon or capsule Grade IIB: With Infection Grade IIC: With ischemia Grade IID: With infection and ischemia

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00014 BG001

Neuropathic foot

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00028 BG00129 BG002

Smoker

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00013 BG00110 BG002

Ankle brachial index, ratio (SD)

The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. ABI has been shown to be a specific and sensitive metric for the diagnosis of Peripheral Arterial Disease (PAD).

Normal ABI ranges from 1.0 - 1.4

Values above 1.4 suggest a noncompressible calcified vessel.

A value below 0.9 is considered diagnostic of PAD.

Values less than 0.5 suggests severe PAD.

(https://stanfordmedicine25.stanford.edu/the25/ankle-brachial-index.html)

Mean

Standard Deviation

Ratio

Title

Denominators

Categories

Title	Measurements
	BG0001.07± 0.23 BG001

HbA1c, % (SD)

Mean

Standard Deviation

Percentage of glycosylated hemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.43± 1.75 BG0018.14± 1.49 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Patients with diabetic foot ulcers

Posted

Count of Participants

Participants

12 weeks

ID	Title	Description
OG000	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 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.
OG001	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. 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.

Units	Counts
Participants	OG00036 OG00137

Title

Denominators

Categories

Title	Measurements
	OG00015 OG0015

Secondary

Absolute Change in Ulcer Area

Absolute change in ulcer area over 12 weeks in cm2

Patients with open ulcers

Posted

Mean

Standard Deviation

cm2

12 weeks

ID	Title	Description
OG000	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 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.
OG001	Placebo	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. 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.

Units	Counts

Secondary

Ulcer Recurrence

Number of diabetic foot ulcers with recurrence at 12 months

Patient with closed diabetic foot ulcers

Posted

Number

Count of wounds with recurrence

12 months

ID	Title	Description
OG000	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 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.
OG001	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. 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.

Units

Secondary

Number of Amputation Events

Number of amputation events during interventional period of the study.

Patients with Index limb amputations

Posted

Number

Count of events

12 weeks

ID	Title	Description
OG000	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 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.
OG001	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. 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.

Units

Secondary

Incidence of Adverse Events

Incidence of serious adverse events and adverse events

Patients with diabetic foot ulcers

Posted

Number

Count of events

54 weeks

ID	Title	Description
OG000	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 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.
OG001	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. 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.

Units

Secondary

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.

Study participants with open and healed ulcers.

Posted

Median

Standard Deviation

units on a scale

12 weeks

ID	Title	Description
OG000	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 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.
OG001	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. 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.

Secondary

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.

Patients with diabetic foot ulcers

Posted

12 weeks

ID	Title	Description
OG000	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 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.
OG001	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. 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.

Secondary

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 to complete wound closure, weeks.

Posted

Mean

Standard Deviation

Weeks

12 weeks or wound closure

ID	Title	Description
OG000	Topical Wound Oxygen Device	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.
OG001	Placebo	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.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 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.	2	36	6	36	6	36
EG001	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. 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.	2	37	7	37	7	37

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Wound Infection	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0003 events3 affected36 at risk EG0012 events2 affected37 at risk
Osteomyelitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events2 affected36 at risk EG0015 events5 affected37 at risk
Hyperglycemic event	Endocrine disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk
Urinary Tract Infection	Renal and urinary disorders	Systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected37 at risk
Necrotic Tissue	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk
Cardiovascular Event	Cardiac disorders	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected37 at risk
UTC Grade II Ulceration	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected37 at risk
Severe Maceration	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected37 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
UTC Grade I Ulcer	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0003 events3 affected36 at risk EG0010 events0 affected37 at risk
Ulcer Decline	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected37 at risk
Minor Infection	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected37 at risk
Minor Osteomyelitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected37 at risk
Minor Necrotic Tissue	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk
Cellulitis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk
Edema	Vascular disorders	Systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected37 at risk
Maceration	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected37 at risk
Deramatitis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk
Contusion	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected37 at risk

ID	Term
D003925	Diabetic Angiopathies
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D016523	Foot Ulcer
D007871	Leg Ulcer
D012883	Skin Ulcer
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D048909	Diabetes Complications
D003920	Diabetes Mellitus
D004700	Endocrine System Diseases
D003929	Diabetic Neuropathies