A Prospective, Randomized, Double-Blind Multicenter Study Comparing CDO Therapy to Standard MWT in the Treatment of DFUs

Not Applicable

Completed

Conditions: Diabetic Foot Ulcer

Interventions: Device: CDO electrochemical tissue oxygenation system
Device: Moist Wound Therapy

Registration Number: NCT01645891

Lead Sponsor: Electrochemical Oxygen Concepts, Inc.

Brief Summary: The purpose of this study was to evaluate the safety and effectiveness of Continuous Diffusion of Oxygen (CDO) therapy for the treatment of Diabetic Foot Ulcers. The primary objective of this study is to evaluate the effectiveness of CDO in combination with standard moist wound therapy (MWT) on wound healing as compared to standard MWT alone.

Detailed Description: This study was a 12-week, randomized, fully blinded, placebo-controlled, parallel group clinical trial evaluating the use of the CDO device for DFUs. The CDO device used was the TransCu O2 System. The study was approved by the Schulman Associates Institutional Review Board (Cincinnati, OH, IRB No. 201202439). Randomisation lists were made by the statistician for each clinical site in blocks of size four with SAS. Devices were labelled by the statistician before shipping to the sites. The sites assigned devices to patients sequentially at randomisation. Both arms received identical treatment (device, dressings, etc.) and the devices were functional in both arms with the exception that the oxygen did not flow to the ulcer in the placebo arm. All devices were functional in that they produced oxygen and displayed the oxygen flow rate. This had the effect that the devices appeared identical, including battery drain and oxygen flow display. The only difference was that the placebo devices did not have any oxygen flowing out of the oxygen supply port. Since the oxygen flow rate (3ml/ hour) is low enough that it cannot be felt by the subjects or physicians, the devices all appeared identical. Similarly, the dressings and offloading boots in each arm were limited and identical. The result was that the patients, doctors, evaluators, sponsor and statistician were all fully-blinded to the treatment arms until the data had been collected and verified, thereby eliminating the placebo effect.

Before assignment of a device, all patients were subjected to a run-in period during which they received standard of care dressings, debridement and off-loading to ensure that the wounds were indeed chronic in nature. There were two inclusion criteria essential to the design of the study to ensure that only chronic wounds were being included: initial or baseline wound size and initial or run-in rate of wound closure. These were defined as: 1) baseline DFU size: the ulcer area as determined by independently-verified digital planimetric analysis during screening through the randomization visit, and 2) run-in ulcer closure rate: the percentage of ulcer closure (percentage wound area reduction, or PWAR) during the run-in period before the placement of the device. All subjects received MWT during the run-in period.

The intent was to find a balance between a short run-in period and robust screening criteria to help ensure that non-chronic wounds were not included in the study. Since the PWAR assessment relied on independently-verified planimetric analysis of wound photos, some subjects were initially placed on a device at the conclusion of the run-in period and subsequently found to be not eligible for failing study inclusion/ exclusion criteria. These subjects were removed as not eligible.

The primary efficacy outcome was complete wound closure, defined as complete re-epithelialization with no drainage as assessed by the treating clinician and confirmed by a blinded observer.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 146

Inclusion Criteria

Subjects 30-90 years of age at the time of Informed Consent
Subjects with type 1 or type 2 Diabetes Mellitus with a non-healing, full-thickness, University of Texas Classification of Diabetic Foot Ulcers Class IA diabetic foot ulcers
Subjects who have an ulcer with a duration of at least 4 weeks, but not greater than 52 weeks at time of screening
Subjects with an index ulcer measuring between 1.5 - 10 cm2 in area after debridement (Area = length x width) at time of Screening 1 and Screening 2, as measured using digital photography & computerized planimetric analysis by Centralized Wound Measuring Center (CWMC)
Subjects with a diabetic foot ulcer(s) at or below the malleoli
Subjects who demonstrates adequate arterial perfusion defined as either:
- transcutaneous oxygen measurements of the dorsum of the foot > 30 mm Hg with a skin perfusion pressure > 30 mm Hg, or an ankle/brachial index (ABI) above 0.7, with documented confirmation of adequate arterial perfusion, or
- a Doppler waveform consistent with adequate flow in the foot (biphasic or triphasic waveforms) at screening, or
- absolute toe pressure of > 30 mm Hg
Subject and/or caregiver must be able and willing to learn and perform the duties of dressing changes
Subjects are able and willing to comply with standardized off-loading regimen (such as a fixed ankle walker)

Exclusion Criteria

Subjects < 30 or > 90 years of age at the time of Informed Consent
- Subjects with Target Ulcers with a duration < 4 weeks or > 52 weeks
- Subjects with ulcers measuring less than 1.5 cm2 or greater than 10 cm2 in area (Area = length x width) after debridement at the time of Screening 1 and Screening 2 to Randomization) or > 50% during the 2 week screening period, as measured using digital photography & computerized planimetric analysis's determined by CWMC.
- Subjects whose ulcer decreased in area by > 30 % during the 1 week screening period
- Subjects with evidence of gangrene on any part of affected limb
- Subjects with active Charcot's foot on the study limb
- Subjects scheduled to undergo vascular surgery, angioplasty or thrombolysis at the time of enrollment
- Subjects with active infection at the time of screening
- Subjects with a target ulcer which has exposed tendons, ligaments, muscle, or bone
- Subjects with active malignancy, excluding non-melanoma skin cancer
- Subjects with a history of malignancy on study limb
- Subjects in whom oral, or IV antibiotic/antimicrobial agents or medications have been used within 2 days (48 hours) of baseline
- Subjects who are currently receiving or has received radiation or chemotherapy within 3 months of randomization
- Subjects who have received growth factor therapy (e.g., autologous platelet-rich plasma gel, becaplermin, bilayered cell therapy, dermal substitute, extracellular matrix) within two weeks of screening
- Subjects who are pregnant at the time of screening
- Subjects who are undergoing active renal dialysis
- Subjects who have a known immune insufficiency, excluding Diabetes Mellitus
- Subjects with a history of peripheral vascular repair within 14 days of screening
- Subjects with a current deep vein thrombosis (DVT)
- Subjects with ulcers due to Raynaud's disease
- Subjects with and ulcer due to acute thrombophlebitis
- Subjects with inadequate perfusion to support healing
- Subjects with necrotic wounds covered with eschar or slough
- Subjects with wounds with fistulae or deep sinus tracts of unknown depth
- Subjects who are receiving palliative care
- Subjects who have a HbA1c > 12% (uncontrolled hyperglycemia)
- Subjects whose target ulcer has a known etiology of: malignancy, burn, collagen vascular disease, sickle cell, vasculopathy, or pyoderma gangrenosum
- Subjects with a documented history of alcohol or substance abuse within 6 months of screening
- Subjects who are currently enrolled or who have participated, within 30 days of screening, in another investigational device, drug or biological trial that may interfere with study results
- Subjects with a known allergy to dressing materials, including occlusive dressings and the adhesives on such dressings

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CDO with standard MWT	CDO electrochemical tissue oxygenation system	CDO (continuously supply pure oxygen) with standard Moist Wound Therapy
Moist Wound Therapy	Moist Wound Therapy	Moist Wound Therapy. De-activated Sham device placed to wound in order to blind patient and study staff.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Complete (100%) Wound Closure Defined as Complete Re-epithelialization Without Drainage	12 weeks or wound closure	Number of Participants with complete (100%) wound closure defined as complete re-epithelialization without drainage before or at week 12

Secondary Outcome Measures

Name	Time	Method
Time to 50% Wound Closure	12 weeks or wound closure	Time to 50% wound closure by using digital photography \& computerized planimetric analysis
Time to 75% Wound Closure	12 weeks or wound closure	Time to 75% wound closure by using digital photography \& computerized planimetric analysis
Time to 100% Wound Closure	12 weeks or wound closure	Time to 100% wound closure by using digital photography \& computerized planimetric analysis

Trial Locations

Locations (29): Premier Foot & Ankle Surgeons
🇺🇸
Tucson, Arizona, United States
Weil Foot & Ankle Institute
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Des Plaines, Illinois, United States
Impact Clinical Trials
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Las Vegas, Nevada, United States
PMG Research of Salisbury
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Salisbury, North Carolina, United States
Foot and Ankle Center
🇺🇸
Haverford, Pennsylvania, United States
Integrated Clinical Research
🇺🇸
Abilene, Texas, United States
Clinical Trials of Texas, Inc., dba Clinical Trials of Arizona, Inc.
🇺🇸
Glendale, Arizona, United States
Associated Foot and Ankle Specialists
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Phoenix, Arizona, United States
Southern Arizona VA Health Care System
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Tucson, Arizona, United States
Sacramento Foot & Ankle Center
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Fair Oaks, California, United States
Roy O. Kroeker, DPM , Inc.
🇺🇸
Fresno, California, United States
Limb Preservation Platform
🇺🇸
Fresno, California, United States
Center for Clinical Research, Inc
🇺🇸
San Francisco, California, United States
The Research Center
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Hialeah, Florida, United States
Phoenix Medical Research
🇺🇸
Miami, Florida, United States
Doctors Research Network
🇺🇸
South Miami, Florida, United States
Orthopedic Research Institute
🇺🇸
West Palm Beach, Florida, United States
Aiyan Diabetes Center
🇺🇸
Martinez, Georgia, United States
Foot and Ankle Specialists of the Mid-Atlantic
🇺🇸
Pasadena, Maryland, United States
Clinical Research Medical Center
🇺🇸
Salt Lake City, Utah, United States
PMG Research of Wilmington, LLC
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Wilmington, North Carolina, United States
Clinical Research Associates of Central PA
🇺🇸
Altoona, Pennsylvania, United States
Richard C. Galperin, DPM, PA
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Dallas, Texas, United States
William Blake Partners, LLC
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Grapevine, Texas, United States
Houston Foot & Ankle
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Houston, Texas, United States
Complete Family Foot Care
🇺🇸
McAllen, Texas, United States
Alamo Clinical Research
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San Antonio, Texas, United States
Clinical Trials of Texas
🇺🇸
San Antonio, Texas, United States
The University of Texas Health Science Center at San Antonio
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San Antonio, Texas, United States