Effectiveness of Bilayered Cellular Matrix in Healing of Neuropathic Diabetic Foot Ulcers: Results of a Multicenter Pilot Trial
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If a patient had more than one ulcer, the study ulcer had to be at least 2cm away from any other ulcer and could not have healed more than 30 percent during the two-week screening period.
Study design. This study was an open-label, multicenter (eight centers in the US), controlled, randomized, parallel-group pilot study of patients with diabetes with neuropathic foot ulcers. The study protocol and written consent form were approved by an independent Institutional Review Board, and the trial was conducted in accordance with the ethical principals originating from the Declaration of Helsinki and in compliance with US and local regulatory requirements. All patients gave written informed consent before study entry.
Patients meeting entrance criteria were enrolled in a two-week screening period, during which protocol-defined standard care treatment was initiated with the study ulcer. Standard care consisted of sharp wound debridement as necessary and a covering of moist saline gauze with a layer of transparent adhesive dressing (OpSite™ Transparent Adhesive Film Dressing, Smith & Nephew Inc., Largo, Florida) and gauze wrap; this dressing was changed twice daily. Sharp debridement of devitalized tissue utilizing a scalpel, tissue nipper, and forceps was performed in the clinic by the investigator. All patients were provided with a pressure relief walker (DH Pressure Relief Walker®, Centec Orthopaedics, Camarillo, California) and encouraged to limit mobility. Activity levels were monitored by reviewing a patient diary at each weekly clinic visit.
At a second visit after 14 days, those patients who continued to meet eligibility criteria were individually assigned to the BCM treatment group or to the control group according to a computer-generated randomization code (Figure 1). Patients in the control treatment group continued with standard therapy for up to 12 weeks or until the ulcer was 100-percent reepithelialized with no drainage or need for protective dressings. Patients in the BCM treatment group received standard therapy plus an application of fresh BCM, which was then covered with a nonadherent dressing and gauze wrap (Adaptic®, Johnson & Johnson Wound Management Worldwide, Somerville, New Jersey). The gauze wrap was changed every 48 to 72 hours as required. Patients in the BCM treatment group received standard therapy plus a new BCM application at each weekly visit for up to six total applications until the ulcer was 100-percent epithelialized (complete healing). If healing had not occurred after six applications, standard care was given to the ulcer for an additional six weeks or until complete healing.
Patients were evaluated weekly for up to 12 weeks until the study ulcer was 100-percent reepithelialized. At each visit, vital signs were taken, ulcer debridement was performed if needed, and the ulcer was assessed. Healing was measured by photography and sterile tracing for planimetry. The investigator also measured wound dimensions and assessed wound drainage, infection, and degree of healing.
Efficacy. The primary measure for ulcer healing was planimetric analysis. Measurements were also made by photographic analysis and direct investigator assessment. Data from all patients who were randomized for the study (intent-to-treat population) were included in the analysis.
For planimetric analysis, the investigator made sterile wound tracings of the open, unepithelialized regions of each ulcer at each visit. Calculation of the perimeter and area of the unhealed regions was made from the tracings by digital scanning and computerized planimetric analysis at a central facility. Personnel performing the measurements were blinded to treatment group assignments. Percentage wound closure over time was calculated based on planimetric measurements.
Ulcers were photographed using a uniform protocol with identical equipment, film, and training at each site.
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