The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial

OBJECTIVE: To determine if a human fibroblast-derived dermal substitute could promote the healing of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A randomized, controlled, multicenter study was undertaken at 35 centers throughout the U.S. and enrolled 314 patients to evaluate complete wound closure by 12 weeks. Patients were randomized to either the Dermagraft treatment group or control (conventional therapy). Except for the application of Dermagraft, treatment of study ulcers was identical for patients in both groups. All patients received pressure-reducing footwear and were allowed to be ambulatory during the study. RESULTS: The results demonstrated that patients with chronic diabetic foot ulcers of >6 weeks duration experienced a significant clinical benefit when treated with Dermagraft versus patients treated with conventional therapy alone. With regard to complete wound closure by week 12, 30.0% (39 of 130) of Dermagraft patients healed compared with 18.3% (21 of 115) of control patients (P = 0.023). The overall incidence of adverse events was similar for both the Dermagraft and control groups, but the Dermagraft group experienced significantly fewer ulcer-related adverse events. CONCLUSIONS: The data from this study show that Dermagraft is a safe and effective treatment for chronic diabetic foot ulcers.     

Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective,randomized, double-blind,placebo-controlled study

OBJECTIVE: Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers. RESEARCH DESIGN AND METHODS: A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1). who healed with intact skin; 2). in whom the study ulcer was improved, unchanged, or impaired; or 3). who were amputated above or below the ankle level, as compared with control subjects. RESULTS: Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided chi(2) test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area >or=50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased >or=50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 +/- 8 weeks in the dalteparin group compared with 16 +/- 7 weeks in placebo group (NS). CONCLUSIONS: The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.     

糖尿病足创面处理研究进展

本文系统阐述了糖尿病足创面修复的机制和意义、时机把握、治疗原则、方法选择原则和技巧。特别强调要以糖尿病足清创和感染处理为基础,阐述了创面修复的方式和方法。针对不同阶段的创面,对遵循相应处理原则做出诠释。列举了近年来一些在创面的不同治疗阶段促愈合所应用的新技术、新方法。同时将糖尿病足创面修复的根本目标是功能康复的观念贯穿文章始终。为临床糖尿病足创面的预防及修复提供有效的治疗方案,进行了经验总结。     

Effects of vacuum-compression therapy on healing of diabetic foot ulcers: randomized controlled trial

A single-blind, randomized controlled trial was conducted to evaluate vacuum-compression therapy (VCT) for the healing of diabetic foot ulcers. Eighteen diabetic patients with foot ulcers were recruited through simple nonprobability sampling. Subjects were randomly assigned to either an experimental or a control group. Before and after intervention, the foot ulcer surface area was estimated stereologically, based on Cavalieri's principle. The experimental group was treated with VCT in addition to conventional therapy for 10 sessions. The control group received only conventional therapy, including debridement, blood glucose control agents, systemic antibiotics, wound cleaning with normal saline, offloading (pressure relief), and daily wound dressings. The mean foot ulcer surface area decreased from 46.88 +/- 9.28 mm(2) to 35.09 +/- 4.09 mm(2) in the experimental group (p = 0.006) and from 46.62 +/- 10.03 mm(2) to 42.89 +/- 8.1 mm(2) in the control group (p = 0.01). After treatment, the experimental group significantly improved in measures of foot ulcer surface area compared with the control group (p = 0.024). VCT enhances diabetic foot ulcer healing when combined with appropriate wound care.     

Human epidermal growth factor enhances healing of diabetic foot ulcers

OBJECTIVE: To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks. RESULTS: Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P = 0.0003). CONCLUSIONS: Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time.     

Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo.

OBJECTIVE--To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS--Thirteen patients entered a randomized, double-blind trial of topically applied CT-102 APST vs. placebo (normal saline) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers. CT-102 APST (Curative Technologies, Setauket, NY) was prepared from homologous platelets and contained multiple growth factors including PDGF, PDAF, EGF, PF-4, TGF-beta, aFGF, and bFGF. Inclusion criteria for subjects included diabetes, ulcer of > 8 wk duration, peri-wound transcutaneous oxygen tension > 30 mmHg, platelet count > 100,000/mm3, and no wound infection. Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume, < 100 cm2 in area, and involved subcutaneous tissue. RESULTS--In the CT-102 group, 5 of 7 ulcers were healed (100% epithelialized) by 15 wk, but only 1 of 6 ulcers was healed by 20 wk with placebo (P < 0.05). Average percent reduction in ulcer area at 20 wk was 94% for CT-102 vs. 73% for placebo. Daily reduction in ulcer volume was 73.8 +/- 42.4 mm3/day (mean +/- SE) for CT-102 vs. 21.8 +/- 8.1 mm3/day for placebo (P < 0.05). Daily reduction in ulcer area was 6.2 +/- 1.8 mm2/day for CT-102 vs. 1.8 +/- 0.4 mm2/day for placebo (P < 0.05). CONCLUSIONS--CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers.     

The role of foot self-care behavior on developing foot ulcers in diabetic patients with peripheral neuropathy: A prospective study

BackgroundAlthough foot self-care behavior is viewed as beneficial for the prevention of diabetic foot ulceration, the effect of foot self-care behavior on the development of diabetic foot ulcer has received little empirical investigation.ObjectiveTo explore the relationship between foot self-care practice and the development of diabetic foot ulcers among diabetic neuropathy patients in northern Taiwan.MethodsA longitudinal study was conducted at one medical center and one teaching hospital in northern Taiwan.ParticipantsA total of 295 diabetic patients who lacked sensitivity to a monofilament were recruited. Five subjects did not provide follow-up data; thus, only the data of 290 subjects were analyzed. The mean age was 67.0 years, and 72.1% had six or fewer years of education.MethodsData were collected by a modified version of the physical assessment portion of the Michigan Neuropathy Screening Instrument and the Diabetes Foot Self-Care Behavior Scale. Cox regression was used to analyze the predictive power of foot self-care behaviors.ResultsA total of 29.3% (n = 85) of diabetic neuropathy patients developed a diabetic foot ulcer by the one-year follow-up. The total score on the Diabetes Foot Self-Care Behavior Scale was significantly associated with the risk of developing foot ulcers (HR = 1.04, 95% CI = 1.01–1.07, p = 0.004). After controlling for the demographic variables and the number of diabetic foot ulcer hospitalizations, however, the effect was non-significant (HR = 1.03, 95% CI = 1.00–1.06, p = 0.061). Among the foot self-care behaviors, lotion-applying behavior was the only variable that significantly predicted the occurrence of diabetic foot ulcer, even after controlling for demographic variables and diabetic foot ulcer predictors (neuropathy severity, number of diabetic foot ulcer hospitalizations, insulin treatment, and peripheral vascular disease; HR = 1.19, 95% CI = 1.04–1.36, p = 0.012).ConclusionsAmong patients with diabetic neuropathy, foot self-care practice may be insufficient to prevent the occurrence of diabetic foot ulcer. Instead, lotion-applying behavior predicted the occurrence of diabetic foot ulcers in diabetic patients with neuropathy. Further studies are needed to explore the mechanism of lotion-applying behavior as it relates to the occurrence of diabetic foot ulcer.     

Electric stimulation as an adjunct to heal diabetic foot ulcers: a randomized clinical trial

OBJECTIVE: To evaluate high-voltage, pulse-galvanic electric stimulation as an adjunct to healing diabetic foot ulcers. DESIGN: Randomized, double-blind, placebo-controlled pilot trial. SETTING: University medical center. PATIENTS: Forty patients with diabetic foot ulcers, consecutively sampled. Twenty patients each assigned to treatment and placebo groups. Five patients (2 treated, 3 placebo) withdrew because of severe infection. INTERVENTIONS: Electric stimulation through a microcomputer every night for 8 hours. The placebo group used identical functioning units that delivered no current. Additional wound care consisted of weekly débridements, topical hydrogel, and off-loading with removable cast walkers. Patients were followed for 12 weeks or until healing, whichever occurred first. MAIN OUTCOME MEASURES: Proportion of wounds that healed during the study period. Compliance with use of device (in hr/wk), rate of wound healing, and time until healing. RESULTS: Sixty-five percent of the patients healed in the group treated with stimulation, whereas 35% healed with placebo (p = .058). After stratification by compliance, a significant difference was identified among compliant patients in the treatment group (71% healed), noncompliant patients in the treatment group (50% healed), compliant patients in the placebo group (39% healed), and noncompliant patients in the placebo group (29% healed, linear-by-linear association = 4.32, p = .038). There was no significant difference in compliance between the 2 groups. CONCLUSION: Electric simulation enhances wound healing when used in conjunction with appropriate off-loading and local wound care.     

Becaplermin: recombinant platelet derived growth factor,a new treatment for healing diabetic foot ulcers

Chronic or non-healing lower extremity ulcerations in diabetics are a significant cause of morbidity and mortality, and account for a large proportion of the financial burden related to the care of diabetics. Lower extremity ulcerations develop primarily as a consequence of neuropathy and the goal in addressing any wound is to re-establish tissue integrity as soon as possible. The healing of wounds is a complex procedure involving multiple growth factors, some of which have multiple effects on different cell types, in particular, platelet derived growth factor (PDGF) is a prominent agent, active in all stages of the healing process. Becaplermin (0.01% Regranex^® gel) is a homodimeric protein produced by recombinant DNA technology through the insertion of the gene for the B chain PDGF into the yeast Saccharomyces cerevisiae. The biological activity of becaplermin is similar to that of indigenous PDGF-BB, specifically, the promotion of chemotactic recruitment and the proliferation of cells involved in wound repair. Becaplermin has undergone extensive animal and human studies, demonstrating that it is highly effective as an adjunctive measure for the healing of ulcerations in the feet of diabetics when used in conjunction with standard wound healing practices. Specifically these practices include the provision of a moist environment free of debris and necrotic tissue, control of infection and optimal weight displacement from the affected area. Becaplermin is safe and easy to use, being applied once-daily and at present, becaplermin is the only growth factor licensed for use in wound healing.     

Becaplermin: recombinant platelet derived growth factor, a new treatment for healing diabetic foot ulcers

Chronic or non-healing lower extremity ulcerations in diabetics are a significant cause of morbidity and mortality, and account for a large proportion of the financial burden related to the care of diabetics. Lower extremity ulcerations develop primarily as a consequence of neuropathy and the goal in addressing any wound is to re-establish tissue integrity as soon as possible. The healing of wounds is a complex procedure involving multiple growth factors, some of which have multiple effects on different cell types, in particular, platelet derived growth factor (PDGF) is a prominent agent, active in all stages of the healing process. Becaplermin (0.01% Regranex gel) is a homodimeric protein produced by recombinant DNA technology through the insertion of the gene for the B chain PDGF into the yeast Saccharomyces cerevisiae. The biological activity of becaplermin is similar to that of indigenous PDGF-BB, specifically, the promotion of chemotactic recruitment and the proliferation of cells involved in wound repair. Becaplermin has undergone extensive animal and human studies, demonstrating that it is highly effective as an adjunctive measure for the healing of ulcerations in the feet of diabetics when used in conjunction with standard wound healing practices. Specifically these practices include the provision of a moist environment free of debris and necrotic tissue, control of infection and optimal weight displacement from the affected area. Becaplermin is safe and easy to use, being applied once-daily and at present, becaplermin is the only growth factor licensed for use in wound healing.     

Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial

OBJECTIVE: We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers. RESEARCH DESIGN AND METHODS: In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit. RESULTS: At the 12-week follow-up visit, 63 (56%) Graftskin-treated patients achieved complete wound healing compared with 36 (38%) in the control group (P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group (P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group. CONCLUSIONS: Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care.     

Long-term outcome and disability of diabetic patients hospitalized for diabetic foot ulcers: a 6.5-year follow-up study

OBJECTIVE—The long-term outcome and functional status of subjects hospitalized for diabetic foot ulcers have been poorly studied and thus are the topics of this study.RESEARCH DESIGN AND METHODS—Ninety-four consecutive diabetic subjects hospitalized for diabetic foot ulcers between January 1998 and December 2000 were prospectively followed for mean ± SD 79.5 ± 13.3 months. We calculated rates of primary healing, new ulcers, amputations, mortality, and disability and evaluated the global therapeutic success (GTS) of foot care management as defined by the association of primary healing without recurrence or disability at the end of follow-up.RESULTS—Follow-up was successful in 89 of 94 subjects (63 men and 31 women; age 63.7 ± 10.8 years). Of these, 69 (77.5%) experienced primary healing without major amputation, 39 (43.8%) underwent amputation (24 minor and 15 major), and 46 died (51.7%), including 23 from cardiovascular events. Forty-two of 69 patients who experienced primary healing (60.9%) had ulcer recurrence. At the end of the follow-up period, 25 patients (28.1%) were dependent and 40 subjects (44.9%) had achieved GTS. Multivariate analysis showed the role of age as an independent predictor of GTS (P < 0.05) and of impaired renal function/albuminuria as independent predictors of healing failure, first amputation, and mortality (P < 0.01).CONCLUSIONS—Despite a satisfactory initial healing rate, the global long-term outcome of patients hospitalized for diabetic foot ulcers was poor. Nephropathy appears to be an important predictor of long-term outcome. Further studies are needed to establish recognized criteria for therapeutic success going beyond just the evaluation of healing rate in the management of diabetic foot ulcers.Diabetic foot ulcers represent a major public health concern (1) and are commonly viewed as a lower-extremity disease associated with a high amputation rate (2). They are generally associated with advanced micro- and macroangiopathy, resulting in excessively high morbidity and mortality (3).Pathogenic mechanisms and therapeutic options for foot ulcers have been extensively studied, leading to an international consensus in 1999 (4). However, most studies have focused on ulcer-related outcomes over short periods of time (healing, change in area, or amputations), rather than evaluation of long-term patient-related outcomes (5–7). Recently, Jeffcoate et al. (8) used the association of survival, absence of any amputation, and freedom from ulcers as an estimate of patient-related outcomes, showing that ulcer-related outcomes may extensively underestimate the true morbidity and mortality associated with diabetic foot disease. However, these authors did not evaluate functional outcome, and their measurements were confined to the first year after initial registration in their clinic. The aim of the present study was to analyze the long-term outcome of diabetic patients after hospitalization for foot ulcers using a scale for disability (9) and to investigate possible prognostic factors.     

Off-loading the diabetic foot wound: a randomized clinical trial

OBJECTIVE--To compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes. RESEARCH DESIGN AND METHODS--In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day). RESULTS--The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1-26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW (P = 0.033) and half-shoe (P = 0.012). Patients were significantly less active in the TCC (600.1 +/- 320.0 daily steps) compared with the half-shoe (1,461.8 +/- 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 +/- 563.3 daily steps, P = 0.67) or the RCW and the half-shoe (P = 0.15). CONCLUSIONS--The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe.     

湿性愈合疗法联合高压氧治疗糖尿病足溃疡的效果

目的 探讨湿性愈合疗法联合高压氧治疗糖尿病足溃疡的应用.方法 通过在临床实践中以传统换药为基础,再使用湿性愈合疗法联合高压氧治疗糖尿病足溃疡,评价患者对该疗法的满意度、切口愈合率、愈合时间、换药次数,并与单独使用传统换药相比较,进行两者之间的差异分析.结果 实验组显效18例（85.7％）,有效3例（14.3％）,对照组显效10例（47.6％）,有效6例（28.6％）,无效5例（23.8％）,两组比较差异有统计学意义（x2=5.68,P＜0.05）;愈合时间实验组需要（27.8±3.75）d,对照组需要（38.6±3.81）d,两组比较差异有统计学意义（t=9.2,P＜0.05）;换药次数实验组需要（15.6±3.45）次,对照组需要（24.8±3.62）次,两组比较差异有统计学意义（t=8.4,P＜0.05）;患者满意度实验组为95.4％优于对照组的68.9％,两组比较差异有统计学意义（t=5.15,P＜0.05）.结论 采用以传统换药为基础,再使用湿性愈合疗法联合高压氧治疗糖尿病足溃疡能明显提高创面愈合率,减少换药次数,减轻护士工作量,其结果可为合理应用该疗法促进糖尿病足溃疡愈合又可减少患者的痛苦提供临床依据.     

Total contact casting of the diabetic foot in daily practice: a prospective follow-up study

OBJECTIVE: A limited number of clinical trials have shown that the total contact cast (TCC) is an effective treatment in neuropathic, noninfected, and nonischemic foot ulcers. In this prospective data collection study, we assessed outcome and complications of TCC treatment in neuropathic patients with and without peripheral arterial disease (PAD) or (superficial) infection. RESEARCH DESIGN AND METHODS: Ninety-eight consecutive patients selected for casting were followed until healing; all had polyneuropathy, 44% had PAD, and 29% had infection. Primary outcomes were percentage healed with a cast, time to heal, and number of complications. RESULTS: Ninety percent of all nonischemic ulcers without infection and 87% with infection healed in the cast (NS). In patients with PAD but without critical limb ischemia, 69% of the ulcers without infection and 36% with infection healed (P < 0.01). In multivariate analyses, PAD, infection, and heel ulcers were associated with a lower percentage healed (all P < 0.05). Median duration of cast treatment was 34 days. New ulcers, all superficial, developed in 9% and preulcerative lesions in 28% of the patients; these skin lesions healed in the cast within a maximum of 13 days. CONCLUSIONS: In comparison to pure neuropathic ulcers, ulcers with moderate ischemia or infection can be treated effectively with casting. However, when both PAD and infection are present or the patient has a heel ulcer, outcome is poor and alternative strategies should be sought. The high rate of preulcerative lesions stresses the importance of close monitoring during TCC treatment.     

Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a removable cast walker (RCW) and an "instant" total contact cast (iTCC) in healing neuropathic diabetic foot ulcerations. RESEARCH DESIGN AND METHODS: We randomly assigned 50 patients with University of Texas grade 1A diabetic foot ulcerations into one of two off-loading treatment groups: an RCW or the same RCW wrapped with a cohesive bandage (iTCC) so patients could not easily remove the device. Subjects were evaluated weekly for 12 weeks or until wound healing. RESULTS: An intent-to-treat analysis showed that a higher proportion of patients had ulcers that were healed at 12 weeks in the iTCC group than in the RCW group (82.6 vs. 51.9%, P = 0.02, odds ratio 1.8 [95% CI 1.1-2.9]). Of the patients with ulcers that healed, those treated with an iTCC healed significantly sooner (41.6 +/- 18.7 vs. 58.0 +/- 15.2 days, P = 0.02). CONCLUSIONS: Modification of a standard RCW to increase patient adherence to pressure off-loading may increase both the proportion of ulcers that heal and the rate of healing of diabetic neuropathic wounds.