TCO2-2012-01 A Prospective, Randomized, Double-Blind Multicenter Study Comparing Continuous Diffusion of Oxygen (CDO) Therapy to Standard Moist Wound Therapy (MWT) in the Treatment of Diabetic Foot Ulcers

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.