The efficacy and safety of Grafix(®) for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial

Lawrence A Lavery, James Fulmer, Karry Ann Shebetka, Matthew Regulski, Dean Vayser, David Fried, Howard Kashefsky, Tammy M Owings, Janaki Nadarajah, Grafix Diabetic Foot Ulcer Study Group, Duncan Grant, Michael Lowhorn, Thomas Hendrick, Dan Streja, Gary Friedlander, Daniel Goldman, Adam Budny, Terry Treadwell, David Ware, Michael Kerzner, Ian Gordon, Lawrence A Lavery, James Fulmer, Karry Ann Shebetka, Matthew Regulski, Dean Vayser, David Fried, Howard Kashefsky, Tammy M Owings, Janaki Nadarajah, Grafix Diabetic Foot Ulcer Study Group, Duncan Grant, Michael Lowhorn, Thomas Hendrick, Dan Streja, Gary Friedlander, Daniel Goldman, Adam Budny, Terry Treadwell, David Ware, Michael Kerzner, Ian Gordon

Abstract

In a randomised, controlled study, we compared the efficacy of Grafix(®) , a human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of patients with complete wound closure by 12 weeks. Secondary endpoints included the time to wound closure, adverse events and wound closure in the crossover phase. The proportion of patients who achieved complete wound closure was significantly higher in patients who received Grafix (62%) compared with controls (21%, P = 0·0001). The median time to healing was 42 days in Grafix patients compared with 69·5 days in controls (P = 0·019). There were fewer Grafix patients with adverse events (44% versus 66%, P = 0·031) and fewer Grafix patients with wound-related infections (18% versus 36·2%, P = 0·044). Among the study subjects that healed, ulcers remained closed in 82·1% of patients (23 of 28 patients) in the Grafix group versus 70% (7 of 10 patients) in the control group (P = 0·419). Treatment with Grafix significantly improved DFU healing compared with standard wound therapy. Importantly, Grafix also reduced DFU-related complications. The results of this well-controlled study showed that Grafix is a safe and more effective therapy for treating DFUs than standard wound therapy.

Keywords: Diabetes; Infection; Stem cells; Ulcer.

© 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Kaplan–Meier analysis of probability of 100% closure for Grafix versus control.

References

    1. Guariguata L, Whiting D, Weil C, Unwin N. The International Diabetes Federation diabetes atlas methodology for estimating global and national prevalence of diabetes in adults. Diabetes Res Clin Pract 2011;94:322–32.
    1. Centers for Disease Control and Prevention (CDC) . 2007 National Diabetes Fact Sheet. Atlanta: CDC, 2008.
    1. American Diabetes A. Economic costs of diabetes in the U.S. in 2012. Diabetes Care 2013;36:1033–46.
    1. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005;293:217–28.
    1. Kantor J, Margolis DJ. Treatment options for diabetic neuropathic foot ulcers: a cost‐effectiveness analysis. Dermatol Surg 2001;27:347–51.
    1. Morbach S, Furchert H, Groblinghoff U, Hoffmeier H, Kersten K, Klauke GT, Klemp U, Roden T, Icks A, Haastert B, Rumenapf G, Abbas ZG, Brarara M, Armstrong DG. Long‐term prognosis of diabetic foot patients and their limbs: amputation and death over the course of a decade. Diabetes Care 2012;35:2021–7.
    1. Markowitz JS, Gutterman EM, Magee G, Margolis DJ. Risk of amputation in patients with diabetic foot ulcers: a claims‐based study. Wound Repair Regen 2006;14:11–7.
    1. Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta‐analysis. Diabetes Care 1999;22:692–5.
    1. Marston WA, Hanft J, Norwood P, Pollak R, Dermagraft Diabetic Foot Ulcer Study Group . The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care 2003;26:1701–5.
    1. Veves A, Falanga V, Armstrong DG, Sabolinski ML, Apilgraft Diabetic Foot Ulcer Study . Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001;24:290–5.
    1. Hanson SE, Bentz ML, Hematti P. Mesenchymal stem cell therapy for nonhealing cutaneous wounds. Plast Reconstr Surg 2010;125:510–6.
    1. Maxson S, Lopez EA, Yoo D, Danilkovitch‐Miagkova A, Leroux MA. Concise review: role of mesenchymal stem cells in wound repair. Stem Cells Transl Med 2012;1:142–9.
    1. Emerson SS, Fleming TR. Symmetric group sequential test designs. Biometrics 1989;45:905–23.
    1. Reyzelman A, Crews RT, Moore JC, Moore L, Mukker JS, Offutt S, Tallis A, Turner WB, Vayser D, Winters C, Armstrong DG. Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study. Int Wound J 2009;6:196–208.
    1. Regulski M, Jacobstein DA, Petranto RD, Migliori VJ, Nair G, Pfeiffer D. A retrospective analysis of a human cellular repair matrix for the treatment of chronic wounds. Ostomy Wound Manage 2013;59:38–43.
    1. Armstrong DG, Lavery LA, Bushman TR. Peak foot pressures influence the healing time of diabetic foot ulcers treated with total contact casts. J Rehabil Res Dev 1998;35:1–5.
    1. Cavanagh PR, Bus SA. Off‐loading the diabetic foot for ulcer prevention and healing. Plast Reconstr Surg 2011;127(Suppl 1):248S–56S.
    1. Lavery LA, Vela SA, Lavery DC, Quebedeaux TL. Reducing dynamic foot pressures in high‐risk diabetic subjects with foot ulcerations. A comparison of treatments. Diabetes Care 1996;19:818–21.
    1. Armstrong DG, Lavery LA, Wu S, Boulton AJ. Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial. Diabetes Care 2005;28:551–4.
    1. Katz IA, Harlan A, Miranda‐Palma B, Prieto‐Sanchez L, Armstrong DG, Bowker JH, Mizel MS, Boulton AJ. A randomized trial of two irremovable off‐loading devices in the management of plantar neuropathic diabetic foot ulcers. Diabetes Care 2005;28:555–9.
    1. Armstrong DG, Nguyen HC, Lavery LA, van Schie CH, Boulton AJ, Harkless LB. Off‐loading the diabetic foot wound: a randomized clinical trial. Diabetes Care 2001;24:1019–22.
    1. Wu SC, Jensen JL, Weber AK, Robinson DE, Armstrong DG. Use of pressure offloading devices in diabetic foot ulcers: do we practice what we preach? Diabetes Care 2008;31:2118–9.
    1. Morona JK, Buckley ES, Jones S, Reddin EA, Merlin TL. Comparison of the clinical effectiveness of different off‐loading devices for the treatment of neuropathic foot ulcers in patients with diabetes: a systematic review and meta‐analysis. Diabetes Metab Res Rev 2013;29:183–93.
    1. Mueller MJ, Diamond JE, Sinacore DR, Delitto A, Blair VP 3rd, Drury DA, Rose SJ. Total contact casting in treatment of diabetic plantar ulcers. Controlled clinical trial. Diabetes Care 1989;12:384–8.
    1. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. J Am Coll Surg 1996;183:61–4.
    1. Saap LJ, Falanga V. Debridement performance index and its correlation with complete closure of diabetic foot ulcers. Wound Repair Regen 2002;10:354–9.
    1. Lavery LA, Peters EJ, Armstrong DG, Wendel CS, Murdoch DP, Lipsky BA. Risk factors for developing osteomyelitis in patients with diabetic foot wounds. Diabetes Res Clin Pract 2009;83:347–52.
    1. Lavery LA, Armstrong DG, Wunderlich RP, Mohler MJ, Wendel CS, Lipsky BA. Risk factors for foot infections in individuals with diabetes. Diabetes Care 2006;29:1288–93.
    1. Lavery LA, Peters EJ, Williams JR, Murdoch DP, Hudson A, Lavery DC, International Working Group on the Diabetic Foot . Reevaluating the way we classify the diabetic foot: restructuring the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care 2008;31:154–6.
    1. Davis J. Skin transplantation with a review of 550 cases at the Johns Hopkins Hospital. John Hopkins Med J 1910;15:307–96.
    1. Sabella N. Use of fetal membranes in skin grafting. Med Records NY 1913;83:478–80.
    1. Stern M. The grafting of unpreserved amniotic membrane to burned and ulcerated skin surfaces substituting skin graft. JAMA 1913;60:973–4.
    1. Arnold Y, Leroux JD, Williams M, Danilkovitch A. A comparison study of the anti‐oxidant effects of cellular versus acellular human repair matrices. In: Symposium on Advanced Wound Care; 2013 May 2–5; Las Vegas (NV).
    1. Arnold Y, Leroux JD, Williams M, Danilkovitch A. A comparison study of the angiogenic effect of cellular versus acellular human repair matrices. In: Symposium on Advanced Wound Care; 2013 May 2–5; Las Vegas (NV).
    1. Arnold Y, Leroux JD, Williams M, Danilkovitch A. A comparison study of the anti‐inflammatory effects of cellular versus acellular human repair matrices. In: Symposium on Advanced Wound Care; 2013 May 2–5; Las Vegas (NV).

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren