A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics.
ABSTRACT: A randomised, controlled multicentre clinical trial was conducted at 14 wound care centres in the United States to confirm the efficacy of dehydrated human amnion/chorion membrane allograft (dHACM) for the treatment of chronic lower extremity ulcers in persons with diabetes. Patients with a lower extremity ulcer of at least 4 weeks duration were entered into a 2-week study run-in phase and treated with alginate wound dressings and appropriate offloading. Those with less than or equal to 25% wound closure after run-in were randomly assigned to receive weekly dHACM application in addition to offloading or standard of care with alginate wound dressings, for 12?weeks. A total of 110 patients were included in the intent-to-treat (ITT) analysis, with n =?54 in the dHACM group and n =?56 in the no-dHACM group. Of the participants, 98 completed the study per protocol, with 47 receiving dHACM and 51 not receiving dHACM. The primary study outcome was percentage of study ulcers completely healed in 12?weeks, with both ITT and per-protocol participants receiving weekly dHACM significantly more likely to completely heal than those not receiving dHACM (ITT-70% versus 50%, P = 0.0338, per-protocol-81% versus 55%, P = 0.0093). A Kaplan-Meier analysis was performed to compare the time-to-healing performance with/without dHACM, showing a significantly improved time to healing with the use of allograft, log-rank P < 0.0187. Cox regression analysis showed that dHACM-treated subjects were more than twice as likely to heal completely within 12?weeks than no-dHACM subjects (HR: 2.15, 95% confidence interval 1.30-3.57, P = 0.003). At the final follow up at 16?weeks, 95% of dHACM-healed ulcers and 86% of healed ulcers in the no-dHACM group remained closed. These results confirm that dHACM is an efficacious treatment for lower extremity ulcers in a heterogeneous patient population.
Project description:The aim of this study was to determine the safety and effectiveness of dehydrated human umbilical cord allograft (EpiCord) compared with alginate wound dressings for the treatment of chronic, non-healing diabetic foot ulcers (DFU). A multicentre, randomised, controlled, clinical trial was conducted at 11 centres in the United States. Individuals with a confirmed diagnosis of Type 1 or Type 2 diabetes presenting with a 1 to 15?cm2 ulcer located below the ankle that had been persisting for at least 30?days were eligible for the 14-day study run-in phase. After 14?days of weekly debridement, moist wound therapy, and off-loading, those with ?30% wound area reduction post-debridement (n?=?155) were randomised in a 2:1 ratio to receive a weekly application of EpiCord (n?=?101) or standardised therapy with alginate wound dressing, non-adherent silicone dressing, absorbent non-adhesive hydropolymer secondary dressing, and gauze bandage roll (n?=?54). All wounds continued to have appropriate off-loading during the treatment phase of the study. Study visits were conducted for 12?weeks. At each weekly visit, the DFU was cleaned and debrided as necessary, with the wound photographed pre- and post-debridement and measured before the application of treatment group-specific dressings. A follow-up visit was performed at week 16. The primary study end point was the percentage of complete closure of the study ulcer within 12?weeks, as assessed by Silhouette camera. Data for randomised subjects meeting study inclusion criteria were included in an intent-to-treat (ITT) analysis. Additional analysis was conducted on a group of subjects (n?=?134) who completed the study per protocol (PP) (EpiCord, n?=?86, alginate, n?=?48) and for those subjects receiving adequate debridement (EpiCord, n?=?67, alginate, n?=?40). ITT analysis showed that DFUs treated with EpiCord were more likely to heal within 12?weeks than those receiving alginate dressings, 71 of 101 (70%) vs 26 of 54 (48%) for EpiCord and alginate dressings, respectively, P = 0.0089. Healing rates at 12?weeks for subjects treated PP were 70 of 86 (81%) for EpiCord-treated and 26 of 48 (54%) for alginate-treated DFUs, P = 0.0013. For those DFUs that received adequate debridement (n?=?107, ITT population), 64 of 67 (96%) of the EpiCord-treated ulcers healed completely within 12?weeks, compared with 26 of 40 (65%) of adequately debrided alginate-treated ulcers, P < 0.0001. Seventy-five subjects experienced at least one adverse event, with a total of 160 adverse events recorded. There were no adverse events related to either EpiCord or alginate dressings. These results demonstrate the safety and efficacy of EpiCord as a treatment for non-healing DFUs.
Project description:Statistical interpretation of data collected in a randomised controlled trial (RCT) is conducted on the intention-to-treat (ITT) and/or the per-protocol (PP) study populations. ITT analysis is a comparison of treatment groups including all patients as originally allocated after randomisation regardless if treatment was initiated or completed. PP analysis is a comparison of treatment groups including only those patients who completed the treatment as originally allocated, although it is often criticised because of its potential to instil bias. A previous report from an RCT conducted to evaluate the efficacy of dehydrated human amnion/chorion membrane allograft (EpiFix) as an adjunct to standard comprehensive wound therapy consisting of moist dressings and multi-layer compression in the healing of venous leg ulcers (VLUs) only reported PP study results (n?=?109, 52 EpiFix and 57 standard care patients), although there were 128 patients randomised: 64 to the EpiFix group and 64 to the standard care group. Primary study outcome was the incidence of healing at 12?weeks. The purpose of the present study is to report ITT results on all 128 randomised subjects and assess if both ITT and PP data analyses arrive at the same conclusion of the efficacy of EpiFix as a treatment for VLU. Rates of healing for the ITT and PP populations were, respectively, 50% and 60% for those receiving EpiFix and 31% and 35% for those in the standard care cohort. Within both ITT and PP analyses, these differences were statistically significant; P = 0.0473, ITT and P = 0.0128, PP. The Kaplan-Meier plot of time to heal within 12?weeks for the ITT and PP populations demonstrated a superior wound-healing trajectory for EpiFix compared with VLUs treated with standard care alone. These data provide clinicians and health policymakers an additional level of assurance regarding the effectiveness of EpiFix.
Project description:BACKGROUND:Over the past generation, preclinical data have suggested that there is a potential physiologic benefit to applying oxygen topically to wounds. However, we are unaware of any studies in the literature that have robustly assessed whether this would lead to a higher proportion of healing in similarly treated people without oxygen. Therefore, the purpose of this study was to assess this in people being treated for chronic diabetic foot ulcers (DFUs). METHODS:We enrolled and randomized 100 subjects with DFUs (79% male, aged 58.3 ± 12.1 years) to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed until closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up. RESULTS:There were no significant differences in assessed descriptive characteristics between the treatment arms ( P > .05 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = .02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = .006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham ( P < .001). CONCLUSIONS:The results of this study suggest that continuously diffused oxygen over a wound leads to significantly higher rates of closure, and faster time to closure, compared to similarly treated patients receiving standard therapy coupled with a sham device. Furthermore, the relative efficacy appears to improve the more the therapy may be needed (more chronic and larger wounds).
Project description:BACKGROUND:Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. METHODS/DESIGN:This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. DISCUSSION:This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. TRIAL REGISTRATION:This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14.
Project description:BACKGROUND:Disease of the pilonidal sinus is a common condition that affects mainly young adults. Options for management include excision of the sinus tracts, leaving the wound open to heal by secondary intention. The aim of this study was to compare wound healing with dialkylcarbamoyl chloride (DACC)-coated dressings versus alginate dressings. METHODS:This multicentre trial randomized consecutive patients undergoing surgery for pilonidal disease to postoperative wound care with either DACC-coated or alginate dressings. The primary outcome was the proportion of wounds healed after 75?days. Secondary outcomes were the local status of wounds during the healing process, the quality assessment of the dressings by the patient, and the time needed to return to usual activities. RESULTS:A total of 246 patients were included: 120 in the DACC-coated group and 126 in the alginate group. In per-protocol analysis, there were significantly more patients with completely healed wounds after 75?days in the DACC group than in the alginate group: 78 of 103 (75·7 per cent) versus 58 of 97 (60 per cent) respectively (odds ratio 2·55, 95 per cent c.i. 1·12 to 5·92; P = 0·023). During follow-up, wounds with alginate dressings had more fibrin than those with DACC-coated dressings, but the difference was not significant (P = 0·079). There was no difference between the two arms in patients' assessment of the dressings. CONCLUSION:The number of wounds completely healed at 75?days was significantly higher for DACC-coated compared with alginate dressings. However, the preplanned, clinically significant improvement in healing of 20 per cent was not reached. Registration number: NCT02011802 ( https://clinicaltrials.gov/).
Project description:Foot ulcers in people with diabetes are a common and serious global health issue. Dressings form a key part of ulcer treatment. Existing systematic reviews are limited by the lack of head-to-head comparisons of alternative dressings in a field where there are several different dressing options. We aimed to determine the relative effects of alternative wound dressings on the healing of diabetic foot ulcers.This study was a systematic review involving Bayesian mixed treatment comparison. We included randomised controlled trials evaluating the effects on diabetic foot ulcer healing of one or more wound dressings. There were no restrictions based on language or publication status.Fifteen eligible studies, evaluating nine dressing types, were included. Ten direct treatment comparisons were made. Whilst there was increased healing associated with hydrogel and foam dressings compared with basic wound contact materials, these findings were based on data from small studies at unclear or high risk of bias. The mixed treatment comparison suggested that hydrocolloid-matrix dressings were associated with higher odds of ulcer healing than all other dressing types; there was a high degree of uncertainty around these estimates, which were deemed to be of very low quality.These findings summarise all available trial evidence regarding the use of dressings to heal diabetic foot ulcers. More expensive dressings may offer no advantages in terms of healing than cheaper basic dressings. In addition, evidence pointing to a difference in favour of 'advanced' dressing types over basic wound contact materials is of low or very low quality.
Project description:Diabetic foot ulcers are frequently related to elevated pressure under a bony prominence. Conservative treatment includes offloading with orthopaedic shoes and custom made orthotics or plaster casts. While casting in plaster is usually effective in achieving primary closure of foot ulcers, recurrence rates are high. Minimally invasive surgical offloading that includes correction of foot deformities has good short and long term results. The surgery alleviates the pressure under the bony prominence, thus enabling prompt ulcer healing, negating the patient's dependence on expensive shoes and orthotics, with a lower chance of recurrence. The purpose of this protocol is to compare offloading surgery (percutaneous flexor tenotomy, mini-invasive floating metatarsal osteotomy or Keller arthroplasty) to non-surgical treatment for patients with diabetic foot ulcers in a semi-crossover designed RCT.One hundred patients with diabetic neuropathy related foot ulcers (tip of toe ulcers, ulcers under metatarsal heads and ulcers under the hallux interphalangeal joint) will be randomized (2:3) to a surgical offloading procedure or best available non-surgical treatment. Group 1 (surgery) will have surgery within 1 week. Group 2 (controls) will be prescribed an offloading cast applied for up to 12 weeks (based on clinical considerations). Following successful offloading treatment (ulcer closure with complete epithelization) patients will be prescribed orthopaedic shoes and custom made orthotics. If offloading by cast for at least 6 weeks fails, or the ulcer recurs, patients will be offered surgical offloading. Follow-up will take place till 2 years following randomization. Outcome criteria will be time to healing of the primary ulcer (complete epithelization), time to healing of surgical wound, recurrence of ulcer, time to recurrence and complications.The high recurrence rate of foot ulcers and their dire consequences justify attempts to find better solutions than the non-surgical options available at present. To promote surgery, RCT level evidence of efficacy is necessary.Israel MOH_2017-08-10_000719. NIH: NCT03414216.
Project description:Objective: To develop a venous leg ulcer (VLU) risk stratification system for use in research and clinical practice.Approach: U.S. Wound Registry data were examined retrospectively and assigned an outcome. Bivariate analysis identified significant variables (p?<?0.05) that were used to create a multivariable logistic regression model. Ulcers with data for wound area at the first visit before debridement were included in regression analysis, which was based on a 90% development sample. The model was validated on a hold-out 10% data sample.Results: The original dataset included 26,713 VLUs, of which 11,773 ulcers were eligible for preliminary analysis and 10,942 ulcers were eligible for regression analysis. The 90% development model included 9,898 ulcers, of which 7,498 healed (75.8%). The 10% validation sample included 1,044 ulcers, of which 809 healed (77.5%). The following variables significantly predicted healing: number of concurrent wounds of any etiology, wound size, wound age (in days), evidence of bioburden/infection, being nonambulatory, and hospitalization for any reason.Innovation: The VLU Wound Healing Index (WHI) is a comprehensive, validated risk stratification model for predicting VLU healing that incorporates patient- and wound-specific variables.Conclusions: The WHI can identify which VLUs most likely require adjunctive therapies to heal, prioritize referral to venous experts, risk-stratify ulcers to create more generalizable clinical trials and understand the impact of clinical interventions. The Centers for Medicare and Medicaid Services accepts this method for reporting VLU outcome under the Quality Payment Program.
Project description:Aim:To describe differences in healing time of diabetic foot ulcers for patients treated at the Copenhagen Wound Healing Center, Bispebjerg Hospital, between the years 1999/2000 and 2011/2012. The Center is highly specialized and receives diabetes patients with hard-to-heal foot ulcers. A further aim is to attempt to find predictors of healing time of diabetic foot ulcers. Methods:A retrospective descriptive study of records from patients with diabetic foot ulcer treated at the Copenhagen Wound Healing Center in 1999, 2000, 2011, or 2012. Follow-up data was collected until the 3rd of August 2018. Results:Median time (range) to healing was 6 (61.3) months in 1999/2000 and 6.6 (67.8) in 2011/2012 (p = 0.2). About 33% of ulcers were healed, 17% were minor or major amputated, and 1.5% were dead within one year in 1999/2000, whereas 30% of ulcers were healed (p = 0.6), 14% were amputated (p = 0.2), and 12.8% were dead within one year in 2011/2012 (p < 0.001). The single factor found significantly associated with longer ulcer duration was infection. Related to shorter ulcer duration were toe localization of the ulcer and good glycemic control. Conclusion:The median time to healing of a diabetic foot ulcer was long, around 6 months and with a high recurrence rate in 1999/2000 as well as in 2011/2012. Some factors were found to be significantly related to healing time, and intervention addressing these may improve the time to heal, although such interpretations must be taken with precaution from the present study and should be proven in randomized prospective intervention trials.
Project description:There are many factors involved in wound healing, and the healing process is not static. The therapeutic effect of modern wound dressings in the clinical management of wounds is documented. However, there are few reports regarding the reasonable selection of dressings for certain types of wounds in the clinic. In this article, we retrospect the history of wound dressing development and the classification of modern wound dressings. In addition, the pros and cons of mainstream modern wound dressings for the healing of different wounds, such as diabetic foot ulcers, pressure ulcers, burns and scalds, and chronic leg ulcers, as well as the physiological mechanisms involved in wound healing are summarized. This article provides a clinical guideline for selecting suitable wound dressings according to the types of wounds.