Alexander M. Reyzelman

Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study

This 12‐week, prospective, randomised, controlled multi‐centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix (AM) (study group) and standard of care (control group) therapies. Eighty‐six patients were randomised into study (47 patients) and control (39 patients) groups. No significant differences in demographics or pre‐treatment ulcer data were calculated. Complete healing and mean healing time were 69·6% and 5·7 weeks, respectively, for the study group and 46·2% and 6·8 weeks, respectively, for the control group. The proportion of healed ulcers between the groups was statistically significant (P = 0·0289), with odds of healing in the study group 2·7 times higher than in the control group. Kaplan–Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate (P = 0·015) for the control group (53·9%) compared with the study group (30·4%). After adjusting for ulcer size at presentation, which was a statistically significant covariate (P = 0·0194), a statistically significant difference in non healing rate between groups was calculated (P = 0·0233), with odds of healing 2·0 times higher in the study versus control group. This study supports the use of single‐application AM therapy as an effective treatment of diabetic, neuropathic ulcers.

A clinical trial of Integra Template for diabetic foot ulcer treatment

Individuals with diabetes mellitus are at an increased risk of developing a diabetic foot ulcer (DFU). This study evaluated the safety and efficacy of Integra Dermal Regeneration Template (IDRT) for the treatment of nonhealing DFUs. The Foot Ulcer New Dermal Replacement Study was a multicenter, randomized, controlled, parallel group clinical trial conducted under an Investigational Device Exemption. Thirty‐two sites enrolled and randomized 307 subjects with at least one DFU. Consented patients were entered into the 14‐day run‐in phase where they were treated with the standard of care (0.9% sodium chloride gel) plus a secondary dressing and an offloading/protective device. Patients with less than 30% reepithelialization of the study ulcer after the run‐in phase were randomized into the treatment phase. The subjects were randomized to the control treatment group (0.9% sodium chloride gel; n = 153) or the active treatment group (IDRT, n = 154). The treatment phase was 16 weeks or until confirmation of complete wound closure (100% reepithelialization of the wound surface), whichever occurred first. Following the treatment phase, all subjects were followed for 12 weeks. Complete DFU closure during the treatment phase was significantly greater with IDRT treatment (51%) than control treatment (32%; p = 0.001) at sixteen weeks. The median time to complete DFU closure was 43 days for IDRT subjects and 78 days for control subjects in wounds that healed. The rate of wound size reduction was 7.2% per week for IDRT subjects vs. 4.8% per week for control subjects (p = 0.012). For the treatment of chronic DFUs, IDRT treatment decreased the time to complete wound closure, increased the rate of wound closure, improved components of quality of life and had less adverse events compared with the standard of care treatment. IDRT could greatly enhance the treatment of nonhealing DFUs.

A randomised controlled 8-week crossover clinical evaluation of the 3M™ Coban™ 2 Layer Compression System versus Profore™ to evaluate the product performance in patients with venous leg ulcers

This study compared a two‐layer (Coban™ 2 Layer) and a four‐layer (Profore™) compression bandage system in venous leg ulcer patients. Participants (n = 81) were enrolled into an 8‐week, randomised, open‐label, ten‐centre, crossover clinical trial. The primary endpoint was bandage slippage measured at each dressing change. Secondary endpoints included wound healing, health‐related quality of life (HRQoL) and patient preference. Mean slippage estimated from a mixed analysis of variance model (697 visits) was 2·48 cm for the two‐layer system and 4·17 cm for the four‐layer system (P < 0·001). There were no significant differences in percent of wounds that healed (Fisher’s exact test, P = 0·30), in wound area reduction (Wilcoxon rank‐sum test, P = 0·88) or in linear healing rate (Wilcoxon rank‐sum test, P = 0·94). The HRQoL Physical Symptoms and Daily Living scores were significantly higher with the two‐layer system (pooled two‐sample t‐test, P < 0·05). Patients had a strong preference for the two‐layer system (72%) than the four‐layer system (22%), with 6% having no preference. In conclusion, the two‐layer system exhibited significantly less bandage slippage than the four‐layer system. While less bandage slippage did not appear to impact wound healing, there was indication that it may have influenced patient preference in favour of the two‐layer system and potentially impacted patients’ HRQoL.

Limb salvage with Chopart's amputation and tendon balancing

For several decades, Choparts amputation has met with some skepticism owing to reports of significant equinus deformity developing soon after the procedure is performed. However, with appropriate tendon balancing, which generally includes anterior tibial tendon transfer and tendo Achillis lengthening, this level of amputation is often more functional than slightly more distal amputations, such as Lisfranc or short transmetatarsal amputations. The authors offer a rationale for this observation, which includes a discussion of the longitudinal and transverse arch concept of the foot. This concept dictates that the shorter the midfoot-level amputation, the more likely the patient is to develop an equinovarus deformity, thus exposing the fifth metatarsal base and cuboid to weightbearing stress and a high risk of ulceration. Choparts amputation, in eliminating the cuboid, often obviates the potential varus deformity and thus can have a more acceptable long-term result.

NorLeu3‐A(1–7) stimulation of diabetic foot ulcer healing: Results of a randomized, parallel‐group, double‐blind, placebo‐controlled phase 2 clinical trial

This randomized, double‐blind, placebo‐controlled Phase 2 clinical trial explored NorLeu3‐A(1–7) (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks’ once‐daily topical treatment with 0.03% DSC127 (n = 26), 0.01% DSC127 (n = 27), or Placebo (n = 24), followed by 20 weeks’ standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent‐to‐treat groups and were comparable. Dose‐response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log‐linear pattern for both intent‐to‐treat and per‐protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo‐treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03%DSC127 (p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers.

Comparative effectiveness of mechanically and electrically powered negative pressure wound therapy devices: A multicenter randomized controlled trial

This study was designed to compare the ultraportable mechanically powered Smart Negative Pressure (SNaP) Wound Care System (Spiracur, Sunnyvale, CA) with the electrically powered Vacuum‐Assisted Closure (VAC) Therapy System (Kinetic Concepts, Inc. [KCI], San Antonio, TX) in a multicenter, comparative efficacy, noninferiority‐powered, randomized controlled trial. We enrolled 132 people with noninfected, nonischemic, nonplantar lower extremity diabetic and venous wounds. Each subject was randomly assigned (1:1) to treatment with either system in conjunction with appropriate off‐loading and compression therapy. The trial evaluated treatment for up to 16 weeks or complete wound closure (defined as complete reepithelialization without drainage). Primary end point analysis of wound size reduction found that SNaP‐treated subjects demonstrated noninferiority to the VAC‐treated subjects at 4, 8, 12, and 16 weeks (p = 0.0030, 0.0130, 0.0051, and 0.0044, respectively). Kaplan–Meier analysis showed no significant difference in complete wound closure between SNaP‐ and VAC‐treated subjects at all time points. Device related adverse events and complications such as infection were also similar between treatment groups. These data support similar wound healing outcomes between the SNaP system and the VAC system in the population studied.

Topical Application of a Gentamicin-Collagen Sponge Combined with Systemic Antibiotic Therapy for the Treatment of Diabetic Foot Infections of Moderate Severity A Randomized, Controlled, Multicenter Clinical Trial

BACKGROUND The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity. METHODS We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n = 38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped. RESULTS On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P = .017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P =.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P ≤ .038) and a reduced time to pathogen eradication (P < .001). Safety data were similar for both groups. CONCLUSIONS Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted.

The Role of Revascularization in Transmetatarsal Amputations

Data from 37 patients who underwent a transmetatarsal amputation from January 1993 to April 1996 were reviewed. The mean age and diabetes duration of the subjects were 54.9 (+/- 13.2) years and 16.6 (+/- 8.9) years, respectively. The follow-up period averaged 42.1 (+/- 11.2) months. At the time of follow-up, 29 (78.4%) of the 37 patients still had foot salvage, 8 (21.6%) had progressed to below-the-knee amputation, and 15 (40.5%) had undergone lower-extremity revascularization. Twelve (80%) of the 15 revascularized patients preserved their transmetatarsal amputation level at a follow-up of 36.4 months. The authors concluded that at a maximum of 3 years follow-up after initial amputation, transmetatarsal amputation was a successful amputation level.

Outcomes of Neuroischemic Wounds Treated by a Multidisciplinary Amputation Prevention Service

BACKGROUND Multidisciplinary amputation prevention teams decrease the frequency of major amputations by increasing the use of revascularization procedures and minor amputations. The outcomes of wound healing, wound recurrence, and ambulatory status are assumed to be improved but are not routinely reported. This study investigates the midterm outcomes of neuroischemic wounds treated by our multidisciplinary team. METHODS A retrospective review of patients with neuroischemic wounds treated at a single institution amputation prevention clinic from March 2012 to July 2013. Patient demographics, wound characteristics, procedural details, and clinical and functional outcomes were reviewed. Clinical end points under study included time to wound healing, reulceration rate, and ambulatory status. RESULTS Over 16 months, there were 202 new patients and 1,355 clinic visits. Ninety-one limbs from 89 patients were treated for complex neuroischemic wounds. In 67% (61 of 91) of limbs, wounds were present for >6 weeks before referral. A history of previous revascularization was present in 39% (31 of 91), and 28% (22 of 91) had a previous minor amputation. Forty-one percent of wounds (38 of 91) were limited to the toes or the forefoot whereas 24% (22 of 91) involved the hindfoot or ankle. A total of 151 podiatric and 86 vascular interventions were performed, with an equal distribution of endovascular and open revascularizations. Complete healing was observed for 59% of wounds (54 of 91) over the observation period (median follow up, 207 days; range 56-561 days), and the average time to full healing was 12 weeks. Hindfoot wounds were predictive of failure to heal (odds ratio, 0.21; P < 0.01; 95% confidence interval, 0.06-0.68). Nineteen percent of patients (17 of 91) developed a new wound in the ipsilateral leg during follow-up. Three major amputations were performed (2 below-knee amputation and 1 above-knee amputation) for a major/minor amputation ratio of 0.06. Ambulatory status was preserved or improved in 74% (67 of 91) of patients. The 30-day readmission rate was 11%, which was lower than that observed (21%) in a contemporaneous but all-inclusive population of lower extremity revascularization procedures performed at our institution. CONCLUSIONS Multidisciplinary limb salvage teams effectively heal wounds and maintain ambulatory status in patients with limb-threatening neuroischemic wounds. Patient specific factors, such as hindfoot or ankle wounds, can adversely influence the outcome. Even with aggressive care, healing can be prolonged and a substantial proportion of patients can be expected to have a recurrence, making subsequent surveillance mandatory. Our data also suggest that a coordinated amputation prevention program may help to minimize hospital readmissions in this high-risk population.

Comparison of negative pressure wound therapy with an ultraportable mechanically powered device vs. traditional electrically powered device for the treatment of chronic lower extremity ulcers: A multicenter randomized-controlled trial

The purpose of this study was to compare the ultraportable mechanically powered Smart Negative Pressure (SNaP®) Wound Care System to the traditional electrically powered Vacuum‐Assisted Closure (VAC®) Therapy System in the treatment of chronic lower extremity wounds. This 12‐center randomized‐controlled trial of patients with noninfected, nonischemic, nonplantar lower extremity wounds had enrolled 65 patients, as of January 5, 2010, at the time of a planned interim analysis. Subjects were randomly assigned to treatment with either the SNaP® or VAC® Systems. The trial evaluated treatment for up to 16 weeks or till complete closure was achieved. Fifty‐three patients (N=27 SNaP®, N=26 VAC®) completed at least 4 weeks of therapy. Thirty‐three patients (N=18 SNaP®, N=15 VAC®) completed the study with either healing or 16 weeks of therapy. At the time of planned interim analysis, no significant differences (p=0.99) in the proportion of subjects healed between the two devices evaluated were found. In addition, the percent wound size reduction between treatment groups was not significantly different at 4, 8, 12, and 16 weeks, with noninferiority analysis at 4 weeks of treatment reaching the p‐value <0.05 significance level (*p=0.019). These interim data suggest no difference in wound closure between the SNaP® System and the VAC® System in the population studied. We look forward to the final analysis results.