Effectiveness of Bilayered Cellular Matrix in Healing of Neuropathic Diabetic Foot Ulcers: Results of a Multicenter Pilot Trial
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Film was processed at a central facility and read in randomized order by two separate wound care experts who were blinded to specific protocol, patient, and visit date. Wounds were classified as unepithelialized, completely epithelialized, or “cannot evaluate” (if precluded by a technical reason). Investigator-assessed wound healing was defined as 100-percent epithelization with no drainage or need for absorbent dressing.
Efficacy was measured as the proportion of ulcers in each treatment group that showed complete healing at the end of active treatment, the mean rate of wound closure from visit to visit for each treatment group, and the cumulative proportion of patients in each treatment group showing complete wound closure over time.
Safety. Incidence of adverse events, withdrawals due to adverse event, incidence of infection at wound site, and vital signs were monitored.
Data analysis. For the continuous variable of wound size, the t-test was used to evaluate the rate of wound closure. Time to healing was evaluated from the Cox Regression Model or Log-Rank Test. For comparison of proportion healed, the Chi-square was used.
Patient demographics and baseline characteristics. The two treatment groups showed similar demographics (Table 1). Descriptive statistics of baseline ulcer characteristics are shown in Table 2. Ulcers were stratified into two categories based on wound area: ulcers of less than or equal to 6cm2 and those > 6cm2. Approximately 70 percent of the ulcers were < 6cm2 in size.
Proportion of ulcers healed at endpoint of study. Within the 12-week study period, 35 percent of all ulcers in the BCM treatment group were completely healed, compared with 20 percent of ulcers in the control treatment group (Figure 2). Examining the stratum of ulcers with baseline size less than or equal to 6cm2 showed that 47 percent of ulcers in the BCM treatment group were completely healed (7/15), compared with 23 percent (3/13) of those in the control treatment group. Ulcers with a baseline area of greater than or equal to 6cm2 showed that none of the ulcers in the BCM group were completely healed (0/5), while 14.3 percent of the wounds receiving standard care alone healed by the 12 week endpoint (1/7).
Rate of reepithelization. The rate of wound closure was calculated based on planimetrically measured total epithelialized area at each visit. The mean rate of wound closure per day was higher for the BCM treatment group (1.8 ± 2.5% per day) than for the control treatment group (1.1 ± 1.9% per day) over the 12-week treatment period (p = 0.0087).
The mean rate of wound closure per day in BCM-treated wounds was 2.2 ± 2.8 percent per day (Table 3) compared to 1.1 ± 1.9 percent per day in those wounds receiving standard care alone (p = .001). Figure 3 illustrates the rates of closure of wounds that were of less than or equal to 6cm2 at baseline. The mean rate of wound closure of the BCM-treated group was significantly higher than that of the standard treatment group during the initial three weeks of treatment, gradually declining to approximately 1.4 percent per day by week 5. The mean rate of healing of wounds in the standard-care treatment group showed an approximately steady rate of 1.1 percent per day during the 12 weeks of treatment.
Safety. There were no treatment-related adverse events in either treatment group. In the BCM treatment group, two patients had infections associated with the study ulcer compared with four patients in the standard treatment group. None of the infections in the BCM treatment group were serious compared with one serious infection in the standard treatment group. Two patients in the BCM treatment group were withdrawn prior to the end of treatment. One patient had an adverse event unrelated to the study treatment, and the second was withdrawn due to treatment failure.
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