Intact Fish Skin Graft vs. Standard of Care in Patients with Neuroischaemic Diabetic Foot Ulcers (KereFish Study): An International, Multicentre, Double-Blind, Randomised, Controlled Trial Study Design and Rationale

Abstract

Background: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. Method: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with Kerecis® Omega3 Wound™ than with standard of care. Conclusion: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.

The Use of Intact Fish Skin Grafts in the Treatment of Necrotizing Fasciitis of the Leg: Early Clinical Experience and Literature Review on Indications for Intact Fish Skin Grafts

“…Apart from NF therapy, iFSGs have already been used in a broad spectrum of clinical situations. Typical and commonly reported indications for iFSGs involve chronic wounds caused by peripheral arterial occlusive disease, chronic venous insufficiency or diabetes mellitus [ 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 38 ]. These reports also describe its successful use in uncovered tendons or bones, as in our second patient.…”

“…Most of these experiences were published as case reports or series. However, one randomized-controlled trial comparing iFSGs versus the standard of care (SOC) in diabetic foot ulcers was recently published, while others are ongoing [ 20 , 21 , 22 , 47 ]. The multi-center RCT by Lantis and colleagues involving 102 patients has shown superior wound healing rates and wound area reduction over the SOC for diabetic foot ulcers treated with iFSGs ( p = 0.0163) at 12 weeks [ 47 ].…”

“…The results of the European Horizon-funded multi-national, multi-center RCT (Odin trial; H2020-EU.3. ; H2020-EU.2.1) and its French subgroup, the KereFish study, are anticipated to be published within this year [ 22 ]. Aside from the typical etiologies of chronic wounds, atypical wounds were successfully treated with iFSGs [ 15 , 33 , 34 , 35 ].…”

“…Diabetes mellitus / Diabetic foot syndrome [15,[17][18][19][20][21][22][23][24]36]; • Chronic Venous Insufficiency / Venous ulcers [15,17,23,24,37];…”

“…The iFSGs are available in several sizes, shapes and variations, including pre-meshed or granulated products in the U.S. market, while the European CE certification of those pre-meshed and granulated products, as well as of larger fish skin grafts, is still pending. The clinical spectrum of iFSGs has been reported in several case reports up to prospective randomized-controlled trials and involves typical and atypical chronic wounds and traumatic wounds, including burns in adult and pediatric patients [ 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”