Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: A phase III multicenter, double-blind, randomized, placebo-controlled trial

Park, Kwang Hwan; Han, Seung Hwan; Hong, Joon Pio; Han, Seung Kyu; Lee, Doo‐Hyung; Kim, Bom Soo; Ahn, Jae Hoon; Lee, Jin Woo

doi:10.1016/j.diabres.2018.06.002

Cited by 81 publications

(91 citation statements)

References 37 publications

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“…This is the key highlight of our study. In this study, the follow-up duration was 12 weeks because many previous similar clinical trials for diabetic wound healing also used 12 weeks for the follow-up duration (13,14,18,(32)(33)(34)(35). For precise assessment of the efficacy of the allogeneic ASC treatment, we excluded external confounding factors that could have affected the treatment such as vascular insufficiency and infection.…”

Section: Discussionmentioning

confidence: 99%

Potential of Allogeneic Adipose-Derived Stem Cell–Hydrogel Complex for Treating Diabetic Foot Ulcers

et al. 2019

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Mesenchymal stem cells (MSCs) may hold great promise for treating diabetic wounds. However, it is difficult for a clinician to use MSCs because they have not been commercialized. Meanwhile, a new commercial drug that contains adipose-derived stem cells (ASCs) has been developed. The purpose of this study was to examine the potential of allogeneic ASC sheets for treating diabetic foot ulcers. Fifty-nine patients with diabetic foot ulcers were randomized to either the ASC treatment group (n = 30) or a control group treated with polyurethane film (n = 29). Either an allogeneic ASC sheet or polyurethane film was applied on diabetic wounds weekly. These wounds were evaluated for a maximum of 12 weeks. Complete wound closure was achieved for 73% in the treatment group and 47% in the control group at week 8. Complete wound closure was achieved for 82% in the treatment group and 53% in the control group at week 12. The Kaplan-Meier median times to complete closure were 28.5 and 63.0 days for the treatment group and the control group, respectively. There were no serious adverse events related to allogeneic ASC treatment. Thus, allogeneic ASCs might be effective and safe to treat diabetic foot ulcers.

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Section: Discussionmentioning

confidence: 99%

Potential of Allogeneic Adipose-Derived Stem Cell–Hydrogel Complex for Treating Diabetic Foot Ulcers

et al. 2019

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“…Both intralesional injections and sprays decrease the transmission time of growth factor into the wound tissue. Recently, a randomized, double-blinded, placebo-controlled, multi-center clinical study assessing efficiency of an EGF spray applied topically twice a day to DFUs showed increased healing compared to control treated with saline spray, with complete healing rates of 73.2% and 50.6% respectively [69]. In two phase III clinical trials, a spray containing 0.01% bFGF was used to treat DFU, but failed to meet the primary outcome of difference in complete healing over 12 weeks compared to the control group (NCT01217476 and NCT01217463).…”

Section: Growth Factorsmentioning

confidence: 99%

The discovery and development of topical medicines for wound healing

Öhnstedt

Tomenius

Vågesjö

et al. 2019

Expert Opinion on Drug Discovery

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Introduction: Chronic, nonhealing skin wounds claim >3% of the health-care budget in industrialized countries, and the incidence is rising. Currently, two parallel trends influence innovations within the field of wound healing: the need to reduce spread of antibiotic resistance and the emerging use of health economy and value-based models. Areas covered: This review focuses on the discovery of drug candidates and development of treatments aiming to enhance wound healing in the heterogeneous group of patients with nonhealing wounds. Expert opinion: Nonhealing wounds are multifaceted and recognized as difficult indications. The majority of products currently in use are medical device dressings, or concepts of negative pressure or hyperbaric oxygen treatment. Global best practice guidelines for the treatment of diabetic foot ulcers recommend debridement, redressing, as well as infection control, and are critical to the lack of coherent clinical evidence for many approved products in active wound care. To accelerate wound healing, there is an emerging trend toward biologics, gene therapy, and novel concepts for drug delivery in research and in the pipeline for clinical trials. Scientific delineation of the therapeutic mechanism of action is, in our opinion, vital for clinical trial success and for an increased fraction of medical products in the pharmaceutical pipeline.

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“…In a large RCT of 167 patients, topical spray treatment with 0.005% rhEGF was found to significantly improve complete ulcer healing at 12 weeks (I: 73.2% vs C: 50.6%, P = .001) and the time required to achieve 50% ulcer area reduction. 101 We also found a small cohort study from 2012, deemed to be at a high risk of bias, which found no difference in healing at 8 weeks following weekly application of topical EGF compared with salinemoistened gauze. 102 One three-arm cohort study reported a higher wound closure index at 6 weeks with the use of EGF or platelet-derived growth factor when compared with placebo but was at a high risk of bias with incomplete reporting of results, and the duration of ulcers, at a mean of 8.9 days at inclusion, was relatively short.…”

Section: Epidermal Growth Factormentioning

confidence: 62%

“…Unfortunately, this latter study was marred by switching those in the control group to the intervention arm after the first 2 weeks. In a large RCT of 167 patients, topical spray treatment with 0.005% rhEGF was found to significantly improve complete ulcer healing at 12 weeks (I: 73.2% vs C: 50.6%, P = .001) and the time required to achieve 50% ulcer area reduction . We also found a small cohort study from 2012, deemed to be at a high risk of bias, which found no difference in healing at 8 weeks following weekly application of topical EGF compared with saline‐moistened gauze .…”

Section: Growth Factors Cellular Products and Cellsmentioning

confidence: 67%

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: a systematic review

Vas

Rayman

Dhatariya

et al. 2020

Diabetes Metabolism Res

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The management of diabetic foot ulcers (DFU) remains a challenge, and there is continuing uncertainty concerning optimal approaches to wound healing. The International Working Group of the Diabetic Foot (IWGDF) working group on wound healing has previously published systematic reviews of the evidence in 2008, 2012 and 2016 to inform protocols for routine care and to highlight areas which should be considered for further study. The working group has now updated this review by considering papers on the interventions to improve the healing of DFU's published between June 2014 and August 2018. Methodological quality of selected studies was independently assessed by a minimum of two reviewers using the recently published 21‐point questionnaire as recommended by IWGDF/European Wound Management Association, as well as the previously incorporated Scottish Intercollegiate Guidelines Network criteria. Of the 2275 papers identified, 97 were finally selected for grading following full text review. Overall, there has been an improvement in study design and a significant rise in the number of published studies. While previous systematic reviews did not find any evidence to justify the use of newer therapies, except for negative pressure wound therapy in post‐surgical wounds, in this review we found additional evidence to support some interventions including a sucrose‐octasulfate dressing, the combined leucocyte, fibrin and platelet patch as well as topical application of some placental membrane products, all when used in addition to usual best care. Nonetheless, the assessment and comparison of published trials remains difficult with marked clinical heterogeneity between studies: in patient selection, study duration, standard of usual care provision and the timing and description of the clinical endpoints.

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Topical epidermal growth factor spray for the treatment of chronic diabetic foot ulcers: A phase III multicenter, double-blind, randomized, placebo-controlled trial

Cited by 81 publications

References 37 publications

Potential of Allogeneic Adipose-Derived Stem Cell–Hydrogel Complex for Treating Diabetic Foot Ulcers

Potential of Allogeneic Adipose-Derived Stem Cell–Hydrogel Complex for Treating Diabetic Foot Ulcers

The discovery and development of topical medicines for wound healing

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: a systematic review

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