Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial.


Journal

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
ISSN: 1524-475X
Titre abrégé: Wound Repair Regen
Pays: United States
ID NLM: 9310939

Informations de publication

Date de publication:
11 2021
Historique:
revised: 01 06 2021
received: 17 10 2020
accepted: 15 06 2021
pubmed: 8 7 2021
medline: 1 2 2022
entrez: 7 7 2021
Statut: ppublish

Résumé

Chronic wounds are estimated to affect over 6 million people annually in the United States with an estimated annual cost of $25 billion. Debridement represents a key step in their management and is considered a basic necessity to induce the functional process of tissue repair. However, there is an unmet need for an efficient rapid acting non-surgical debridement agent. Bromelain-based enzymatic debridement has been proven to provide an effective, selective and safe non-surgical debridement in deep burns. EscharEx (MediWound Ltd, Yavne, Israel), is a bromelain-based enzymatic debridement agent currently in development for chronic wounds. The aim of this study was to assess its safety and efficacy in chronic wounds. Seventy-three patients suffering from a lower extremity ulcer of diabetic/venous insufficiency/post-surgical/traumatic aetiology were enrolled in a multicentre, assessor blinded, randomized controlled trial. Patients were randomized to topical treatment by either EscharEx or its gel vehicle for up to 10 daily 4 hour applications, and then continued follow-up for up to 6 months. The EscharEx arm achieved a significantly higher incidence of complete debridement compared to the gel vehicle arm; 55 versus 29% (p = .047), thus meeting the primary endpoint of this study. The EscharEx and gel vehicle arms achieved similar reductions in wound area, non-viable tissue area and wound healing scores during the debridement period. There were no significant differences between the arms in the incidence of complete wound closure (41% in the EsxcharEx arm vs. 53% in the gel vehicle arm) and in the mean time to complete wound closure (70.0 ± 32.8 days in the EsxcharEx arm vs. 65.7 ± 38.4 days in gel vehicle arm). There were no significant safety issues and EscharEx demonstrated a favourable benefit to risk profile.

Identifiants

pubmed: 34231281
doi: 10.1111/wrr.12958
doi:

Substances chimiques

Bromelains 9001-00-7

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

899-907

Informations de copyright

© 2021 The Wound Healing Society.

Références

Järbrink K, Ni G, Sönnergren H, et al. Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review. Syst Rev. 2016;5(1):152.
Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763-771.
Hajhosseini B, Chiou GJ, Dori G, et al. Er:YAG laser vs. sharp debridement in management of chronic wounds: effects on pain and bacterial load. Wound Repair Regen. 2020;28(1):118-125.
Brem H, Stojadinovic O, Diegelmann RF, et al. Molecular markers in patients with chronic wounds to guide surgical debridement. Mol Med. 2007;13(1-2):30-39.
Wicke C, Bachinger A, Coerper S, Beckert S, Witte MB, Königsrainer A. Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized Wound Care Center. Wound Repair Regen. 2009;17(1):25-33.
Bradley M, Cullum N, Sheldon T. The debridement of chronic wounds: a systematic review. Health Technol Assess. 1999;3(17 Pt 1):iii-iv. 1-78.
Cardinal M, Eisenbud DE, Armstrong DG, et al. Serial surgical debridement: a retrospective study on clinical outcomes in chronic lower extremity wounds. Wound Repair Regen. 2009;17(3):306-311.
Doerler M, Reich-Schupke S, Altmeyer P, Stücker M. Impact on wound healing and efficacy of various leg ulcer debridement techniques. J Dtsch Dermatol Ges. 2012;10(9):624-632.
Gethin G, Cowman S, Kolbach DN. Debridement for venous leg ulcers. Cochrane Database Syst Rev. 2015;2015(9):CD008599.
Rosenberg L, Krieger Y, Bogdanov-Berezovski A, Silberstein E, Shoham Y, Singer AJ. A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT. Burns. 2014;40(3):466-474.
Rosenberg L, Shoham Y, Krieger Y, et al. Minimally invasive burn care: a review of seven clinical studies of rapid and selective debridement using a bromelain-based debriding enzyme (Nexobrid). Ann Burns Fire Disasters. 2015;28(4):264-274.
Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004;30(8):843-850.
Rosenberg L, Krieger Y, Silberstein E, et al. Selectivity of a bromelain based enzymatic debridement agent: a porcine study. Burns. 2012;38(7):1035-1040.
Singer AJ, McClain SA, Taira BR, Rooney J, Steinhauff N, Rosenberg L. Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis. J Burn Care Res. 2010;31(2):304-309.
Krieger Y, Bogdanov-Berezovsky A, Gurfinkel R, Silberstein E, Sagi A, Rosenberg L. Efficacy of enzymatic debridement of deeply burned hands. Burns. 2012;38(1):108-112.
Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy using an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model. J Trauma. 2005;58(6):1259-1264.
Schulz A, Fuchs PC, Rothermundt I, et al. Enzymatic debridement of deeply burned faces: healing and early scarring based on tissue preservation compared to traditional surgical debridement. Burns. 2017;43(6):1233-1243.
Schulz A, Perbix W, Shoham Y, et al. Our initial learning curve in the enzymatic debridement of severely burned hands-management and pit falls of initial treatments and our development of a post debridement wound treatment algorithm. Burns. 2017;43(2):326-336.
Singer AJ, Taira BR, Anderson R, McClain SA, Rosenberg L. The effects of rapid enzymatic debridement of deep partial-thickness burns with Debrase on wound reepithelialization in swine. J Burn Care Res. 2010;31(5):795-802.
Hirche C, Citterio A, Hoeksema H, et al. Eschar removal by bromelain based enzymatic debridement (Nexobrid) in burns: an European consensus. Burns. 2017;43(8):1640-1653.
Shoham Y, Krieger Y, Tamir E, et al. Bromelain-based enzymatic debridement of chronic wounds: a preliminary report. Int Wound J. 2018;15(5):769-775.
Gould L, Li WW. Defining complete wound closure: closing the gap in clinical trials and practice. Wound Repair Regen. 2019;27(3):201-224.
Woodbury MG, Houghton PE, Campbell KE, Keast DH. Development, validity, reliability, and responsiveness of a new leg ulcer measurement tool. Adv Skin Wound Care. 2004;17(4 Pt 1):187-196.
Strohal R, Dissemond J, Jordan O'Brien J, et al. EWMA document: debridement. An updated overview and clarification of the principle role of debridement. J Wound Care. 2013;22(1):5.
Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther. 2017;34(3):599-610.
Milne CT, Ciccarelli A, Lassy M. A comparison of collagenase to hydrogel dressings in maintenance debridement and wound closure. Wounds. 2012;24(11):317-322.
Roberts C, Torgerson DJ. Understanding controlled trials: baseline imbalance in randomised controlled trials. BMJ. 1999;319(7203):185.
Margolis DJ, Berlin JA, Strom BL. Risk factors associated with the failure of a venous leg ulcer to heal. Arch Dermatol. 1999;135(8):920-926.
Harding KG, Moore K, Phillips TJ. Wound chronicity and fibroblast senescence-implications for treatment. Int Wound J. 2005;2(4):364-368.
Briggs M, Nelson EA. Local interventions for pain in venous leg ulcers. J Tissue Viability. 1999;9(4):139.
Hofman D, Ryan TJ, Arnold F, et al. Pain in venous leg ulcers. J Wound Care. 1997;6(5):222-224.
Docking R, Boateng J, Catanzano O, Schofield P. A preliminary study of pain relieving dressings for older adults with chronic leg ulcers from the provider's perspective: a qualitative study. J Pain Palliat Care Pharmacother. 2018;32(2-3):71-81.
König M, Vanscheidt W, Augustin M, Kapp H. Enzymatic versus autolytic debridement of chronic leg ulcers: a prospective randomised trial. J Wound Care. 2005;14(7):320-323.
Milne CT, Ciccarelli AO, Lassy M. A comparison of collagenase to hydrogel dressings in wound debridement. Wounds. 2010;22(11):270-274.
Jimenez JC, Agnew PS, Mayer P, et al. Enzymatic debridement of chronic nonischemic diabetic foot ulcers: results of a randomized, controlled trial. Wounds. 2017;29(5):133-139.
Motley TA, Caporusso JM, Lange DL, Eichelkraut RA, Cargill DI, Dickerson JE Jr. Clinical outcomes for diabetic foot ulcers treated with clostridial collagenase ointment or with a product containing silver. Adv Wound Care (New Rochelle). 2018;7(10):339-348.

Auteurs

Yaron Shoham (Y)

Plastic and Reconstructive Surgery Department and Burn Unit, Soroka University Medical Center, Beer Sheba, Israel.
Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheba, Israel.

Eyal Shapira (E)

Plastic and Reconstructive Surgery Department, Shamir Medical Center, Zerifin, Israel.

Josef Haik (J)

Plastic and Reconstructive Surgery Department and Burn Center, Sheba Medical Center, Tel Hashomer, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Moti Harats (M)

Plastic and Reconstructive Surgery Department and Burn Center, Sheba Medical Center, Tel Hashomer, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Talpiot Leadership Program, Shamir Medical Center, Tel Hashomer, Israel.
Institute for Health Research, University of Notre Dame, Fremantle, Western Australia, Australia.

Dana Egozi (D)

Plastic and Reconstructive Surgery Department, Kaplan Medical Center, Rehovot, Israel.
Hebrew University Medical School, Jerusalem, Israel.

Dror Robinson (D)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Orthopedic Surgery Department, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel.

Leonid Kogan (L)

Plastic Surgery and Burns Department, Galilee Medical Center, Naharia, Israel.

Rania Elkhatib (R)

Plastic and Reconstructive Surgery Department, Rambam Health Care Campus, Haifa, Israel.

Geza Telek (G)

Surgery Department, South Pest Central Hospital, National Institute of Hematology and Infectious Diseases, and 1st. Department of Surgery and Interventional Gastroenterology (DPC Surgical Department Group), Faculty of Medicine, Faculty of Dentistry, Semmelweis University, Budapest, Hungary.

Avshalom Shalom (A)

Plastic and Reconstructive Surgery Department, Meir Medical Center, Kfar Saba, Israel.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH