Dardari D, Piaggesi A, Potier L, Sultan A, Diener H, Francois M, Dorweiler B, Bouillet B, M'Bemba J, Chaillous L, Clerici G, Kessler L, Wetzel-Roth W, Storck M, Davidsson OB, Baldursson B, Kjartansson H, Lantis JC, Charpentier G, et al.
NEJM evidence. Date of publication 2024 Dec 1;volume 3(12):EVIDoa2400171.
1. NEJM Evid. 2024 Dec;3(12):EVIDoa2400171. doi: 10.1056/EVIDoa2400171. Epub 2024
Oct 4.
Intact Fish Skin Graft to Treat Deep Diabetic Foot Ulcers.
Dardari D(1)(2), Piaggesi A(3), Potier L(4)(5), Sultan A(6)(7), Diener H(8),
Francois M(9), Dorweiler B(10), Bouillet B(11)(12), M'Bemba J(13), Chaillous
L(14), Clerici G(15)(16), Kessler L(17), Wetzel-Roth W(18), Storck M(19),
Davidsson OB(20), Baldursson B(21), Kjartansson H(21), Lantis JC(22),
Charpentier G(23).
Author information:
(1)Diabetology Department, Center Hopitalier Sud Francilien, Corbeil-Essonnes,
France.
(2)LBEPS, Université d'Evry, IRBA, Université Paris Saclay, 91025 Evry, France.
(3)Diabetic Foot Section, Department of Endocrinology and Metabolism, University
Hospital Pisa, Pisa, Italy.
(4)Diabetology Department, Hôpital Bichat - Claude Bernard, AP-HP, 75018 Paris,
France.
(5)Institut Necker Enfants Malades, Université Paris Cité, INSERM U1151, CNRS
UMR-S8253, F-75015 Paris, France.
(6)Diabetology Nutrition Department, CHU Montpelier, Université de Montpellier,
34090 Montpellier, France.
(7)Inserm, CNRS, Phymedexp, CHU de Montpellier, 34090 Montpellier, France.
(8)Department of Vascular and Endovascular Surgery, Wound Competence Center,
Krankenhaus Bucholz, Buchholz, Germany.
(9)Diabetology Department, CHU de Reims Hôpital Robert Debré, 51100 Reims,
France.
(10)Department of Vascular and Endovascular Surgery, University of Cologne,
Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
(11)Department of Endocrinology, Diabetology and Nutrition, Dijon Bourgogne
University Hospital, 21000 Dijon, France.
(12)INSERM Research Center U1231 CMT, University of Burgundy, 21000 Dijon,
France.
(13)Department of Diabetology, CHU Cochin, Hôpital Cochin, 75000 Paris, France.
(14)Department of Endocrinology-Diabetology-Nutrition, L'Institut du Thorax, CHU
de Nantes, University Hospital of Nantes, 44000 Nantes, France.
(15)San Carlo Hospital, Paderno-Dugnano, Italy.
(16)Gruppo Ospedaliero Leonardo Abano Terme (Padua).
(17)Department of Endocrinology, Diabetes and Nutrition, University Hospital of
Strasbourg, UMR Inserm 1260, Regenerative Nanomedicine, University of Strasbourg
67000 Strasbourg, France.
(18)Belegarzt Wertachkliniken, Munich, Germany.
(19)Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.
(20)Frameshift, Richard Mortensens Vej, DK-2300 Copenhagen, Denmark.
(21)National University Hospital, Reykjavik, Iceland.
(22)Mount Sinai Hospital, New York, New York, USA.
(23)CERITD (Center for Study and Research for Improvement of the Treatment of
Diabetes), Bioparc-Genopole Evry-Corbeil, 91042 Evry, France.
Comment in
NEJM Evid. 2024 Dec;3(12):EVIDe2400373. doi: 10.1056/EVIDe2400373.
BACKGROUND: Diabetic foot ulcers are chronic, difficult to heal, and potentially
life-threatening. Few medical devices have been studied in diabetic ulcers
penetrating to bone or tendon.
METHODS: We conducted an international, open-label randomized controlled trial,
randomly assigning patients with diabetic ulcers penetrating to bone, joint, or
tendon 1:1 to intact fish skin graft or standard wound care, with assigned
treatment applied through 14 weeks. The primary end point was the proportion of
ulcers healed at 16 weeks, defined as reepithelization as identified by the
investigator, and confirmed 14 days later. A blinded adjudication committee
confirmed healing at both time points. Healing was also assessed at 20 and 24
weeks.
RESULTS: Between July 2020 and November 2022, 255 patients were randomly
assigned to intact fish skin graft (n=129) or standard of care (n=126). Healing
was achieved in 44% of patients at 16 weeks with intact fish skin graft compared
with 26% for standard of care (P<0.001, unadjusted), with additional healing at
20 weeks (46% vs. 32%) and 24 weeks (55% vs. 38%). Mean (SD) time to healing was
17.3 (0.69) weeks (95% confidence interval [CI], 15.5 to 18.7) for the intact
fish skin graft group and 19.4 (0.66) weeks (95% CI, 18.1 to 20.7) for the
standard of care group. In a Cox regression, intact fish skin graft was
associated with faster time to healing (hazard ratio, 1.59; 95% CI, 1.07 to
2.36). Primary wound infections were the most common adverse event, occurring in
39 (30.2%) of patients in the intact fish skin graft group and 31 (24.6%) of
patients in the standard of care group.
CONCLUSIONS: Among patients with deep diabetic foot ulcers, treatment with
intact fish skin graft was superior to standard of care in proportion of wounds
healed at 16 weeks and was associated with faster time to healing. (Funded by
European Commission Fast Track to Innovation Horizon 2020, and Kerecis Ltd.
ClinicalTrials.gov NCT04257370.).
DOI: 10.1056/EVIDoa2400171
PMID: 39365895 [Indexed for MEDLINE]
