A prospective, double-blind, randomized, controlled clinical trial comparing standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care only for the treatment of chronic, non-healing ulcers of the lower limb in patients with diabetes mellitus: a study protocol

Daria O'Reilly, Ron Linden, Ludwik Fedorko, Jean-Eric Tarride, Wilhelmine Giffening Jones, James M Bowen, Ron Goeree, Daria O'Reilly, Ron Linden, Ludwik Fedorko, Jean-Eric Tarride, Wilhelmine Giffening Jones, James M Bowen, Ron Goeree

Abstract

Background: It has been suggested that the use of adjunctive hyperbaric oxygen therapy improves the healing of diabetic foot ulcers, and decreases the risk of lower extremity amputations. A limited number of studies have used a double blind approach to evaluate the efficacy of hyperbaric oxygen therapy in the treatment of diabetic ulcers. The primary aim of this study is to assess the efficacy of hyperbaric oxygen therapy plus standard wound care compared with standard wound care alone in preventing the need for major amputation in patients with diabetes mellitus and chronic ulcers of the lower limb.

Methods/design: One hundred and eighteen (59 patients per arm) patients with non-healing diabetic ulcers of the lower limb, referred to the Judy Dan Research and Treatment Centre are being recruited if they are at least 18 years of age, have either Type 1 or 2 diabetes with a Wagner grading of foot lesions 2, 3 or 4 on lower limb not healing for at least 4 weeks. Patients receive hyperbaric oxygen therapy every day for 6 weeks during the treatment phase and are provided ongoing wound care and weekly assessments. Patients are required to return to the study centre every week for an additional 6 weeks of follow-up for wound evaluation and management. The primary outcome is freedom from having, or meeting the criteria for, a major amputation (below knee amputation, or metatarsal level) up to 12 weeks after randomization. The decision to amputate is made by a vascular surgeon. Other outcomes include wound healing, effectiveness, safety, healthcare resource utilization, quality of life, and cost-effectiveness. The study will run for a total of about 3 years.

Discussion: The results of this study will provide detailed information on the efficacy of hyperbaric oxygen therapy for the treatment of non-healing ulcers of the lower limb. This will be the first double-blind randomized controlled trial for this health technology which evaluates the efficacy of hyperbaric oxygen therapy in prevention of amputations in diabetic patients.

Trial registration: ClinicalTrials.gov Identifier: NCT00621608.

Figures

Figure 1
Figure 1
Study Schema.

References

    1. Moss SE, Klein R, Klein BE. Long-term incidence of lower-extremity amputations in a diabetic population. Arch Fam Med. 1996;5(7):391–8. doi: 10.1001/archfami.5.7.391.
    1. Bild DE, Selby JV, Sinnock P, Browner WS, Braveman P, Showstack JA. Lower-extremity amputation in people with diabetes. Epidemiology and prevention. Diabetes Care. 1989;12(1):24–31.
    1. Humphrey AR, Dowse GK, Thoma K, Zimmet PZ. Diabetes and nontraumatic lower extremity amputations. Incidence, risk factors, and prevention--a 12-year follow-up study in Nauru. Diabetes Care. 1996;19(7):710–4. doi: 10.2337/diacare.19.7.710.
    1. Lehto S, Ronnemaa T, Pyorala K, Laakso M. Risk factors predicting lower extremity amputations in patients with NIDDM. Diabetes Care. 1996;19(6):607–12. doi: 10.2337/diacare.19.6.607.
    1. Brauchle M, Funk JO, Kind P, Werner S. Ultraviolet B and H2O2 are potent inducers of vascular endothelial growth factor expression in cultured keratinocytes. J Biol Chem. 1996;271(36):21793–7. doi: 10.1074/jbc.271.36.21793.
    1. Faglia E, Mantero M, Caminiti M, Caravaggi C, De GR, Pritelli C, Clerici G, Fratino P, De CP, Dalla PL, Mariani G, Poli M, Settembrini PG, Sciangula L, Morabito A, Graziani L. Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers: clinical results of a multicentric study of 221 consecutive diabetic subjects. J Intern Med. 2002;252(3):225–32. doi: 10.1046/j.1365-2796.2002.01015.x.
    1. Faglia E, Favales F, Quarantiello A, Calia P, Clelia P, Brambilla G, Rampoldi A, Morabito A. Angiographic evaluation of peripheral arterial occlusive disease and its role as a prognostic determinant for major amputation in diabetic subjects with foot ulcers. Diabetes Care. 1998;21(4):625–30. doi: 10.2337/diacare.21.4.625.
    1. Ramsey SD, Newton K, Blough D, McCulloch DK, Sandhu N, Reiber GE, Wagner EH. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999;22(3):382–7. doi: 10.2337/diacare.22.3.382.
    1. Valensi P, Girod I, Baron F, Moreau-Defarges T, Guillon P. Quality of life and clinical correlates in patients with diabetic foot ulcers. Diabetes Metab. 2005;31(3 Pt 1):263–71. doi: 10.1016/S1262-3636(07)70193-3.
    1. Muller IS, de Grauw WJ, van Gerwen WH, Bartelink ML, van Den Hoogen HJ, Rutten GE. Foot ulceration and lower limb amputation in type 2 diabetic patients in dutch primary health care. Diabetes Care. 2002;25(3):570–4. doi: 10.2337/diacare.25.3.570.
    1. Faglia E, Favales F, Aldeghi A, Calia P, Quarantiello A, Barbano P, Puttini M, Palmieri B, Brambilla G, Rampoldi A, Mazzola E, Valenti L, Fattori G, Rega V, Cristalli A, Oriani G, Michael M, Morabito A. Change in major amputation rate in a center dedicated to diabetic foot care during the 1980s: prognostic determinants for major amputation. Journal of Diabetes & its Complications. 1998;12(2):96–102.
    1. National Diabetes Education Program. Foot health and diabetes: prevalence of foot symptoms and complications. National Diabetes Education ProgramBethesda (MD) National Insitutes of Health; 2004.
    1. Abbott CA, Carrington AL, Ashe H, Bath S, Every LC, Griffiths J, Hann AW, Hussein A, Jackson N, Johnson KE, Ryder CH, Torkington R, Van Ross ER, Whalley AM, Widdows P, Williamson S, Boulton AJ. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med. 2002;19(5):377–84. doi: 10.1046/j.1464-5491.2002.00698.x.
    1. Cianci P, Petrone GJ, Shapiro RL, Ross J, Lueders HW. Proceedings of IXth International Symposium on Underwater and Hyperbaric Physiology. Bethesda, MD: Undersea and Hyperbaric Medical Society; 1987. Economic considerations on the impact of adjunctive hyperbaric oxygen in potential amputees; pp. 1075–9.
    1. Kalani M, Jorneskog G, Naderi N, Lind F, Brismar K. Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot ulcers. Long-term follow-up. Journal of Diabetes & its Complications. 2002;16(2):153–8.
    1. Faglia E, Favales F, Aldeghi A, Calia P, Quarantiello A, Oriani G, Michael M, Campagnoli P, Morabito A. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. Diabetes Care. 1996;19(12):1338–43. doi: 10.2337/diacare.19.12.1338.
    1. Doctor N, Pandya S, Supe A. Hyperbaric oxygen therapy in diabetic foot. J Postgrad Med. 1992;38(3):112–4. 111.
    1. Baroni G, Porro T, Faglia E, Pizzi G, Mastropasqua A, Oriani G, Pedesini G, Favales F. Hyperbaric oxygen in diabetic gangrene treatment. Diabetes Care. 1987;10(1):81–6. doi: 10.2337/diacare.10.1.81.
    1. Abidia A, Laden G, Kuhan G, Johnson BF, Wilkinson AR, Renwick PM, Masson EA, McCollum PT. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg. 2003;25(6):513–8. doi: 10.1053/ejvs.2002.1911.
    1. Kessler L, Bilbault P, Ortega F, Grasso C, Passemard R, Stephan D, Pinget M, Schneider F. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care. 2003;26(8):2378–82. doi: 10.2337/diacare.26.8.2378.
    1. Grim PS, Gottlieb LJ, Boddie A, Batson E. Hyperbaric oxygen therapy. Journal of the American Medical Association. 1990;263(16):2216–20. doi: 10.1001/jama.263.16.2216.
    1. Warriner RA, III, Hopf HW. In: Hyperbaric Oxygen 2003: Indications and Results: The Hyperbaric Oxygen Therapy Committee Report. J. J. Feldmeier, editor. Dunkirk; 2003. Enhancement of healing in selected problem wounds; pp. 41–55.
    1. Clark J. In: Hyperbaric Oxygen 2003: Indications and Results: The Hyperbaric Oxygen Therapy Committee Report. J. J. Feldmeier, editor. Dunkirk; 2007. Side effects and complications; pp. 137–41.
    1. Londahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care. 2010;33(5):998–1003. doi: 10.2337/dc09-1754.
    1. Zamboni WA, Wong HP, Stephenson LL, Pfeifer MA. Evaluation of hyperbaric oxygen for diabetic wounds: a prospective study. Undersea Hyperb Med. 1997;24(3):175–9.
    1. Cianci PE, Petrone GJ, Drager S, Lueders HW. Salvage of the problem wound and potential amputation wiht wound care and adjunctive hyperbaric oxygen therapy. J Hyperb Med. 1988;3:127–41.
    1. Oriani G, Meazza D, Favales F, Pizzi G, Aldeghi A, Faglia E. Hyperbaric oxygen therapy in diabetic gangrene. J Hyperb Med. 1990;5:171–5.
    1. Oriani G, Michael M, Meazza D, Sacchi C, Ronzio A, Montino O, Sala G, Campagnoli P. Diabetic foot and hyperbaric oxygen therapy: a ten-year experience. J Hyperb Med. 1992;7:213–21.
    1. Mitton C, Hailey D. Health technology assessment and policy decisions on hyperbaric oxygen treatment. Int J Technol Assess Health Care. 1999;15(4):661–70.
    1. Wang C, Lau J, New England Medical Center EPC. Technology assessments for hyperbaric oxygen therapy for hypoxic wounds and diabetic wounds of the lower extremities (CAG-00060N) Boston: Agency for Healthcare Research and Quality (AHRQ); 2001.
    1. Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS) Hyperbaric oxygen therapy in Quebec. Montreal: L'Agence; 2000.
    1. Medical Services Advisory Committee. Hyperbaric oxygen therapy. 2001.
    1. Medical Advisory Secretariat. Hyperbaric oxygen therapy for non-healing ulcers in diabetes mellitus. Ontario Ministry of Health and Long-Term Care; 2005.
    1. Hailey D, Jacobs P, Perry DC, Chuck A, Morrison A, Boudreau R. Adjunctive Hyperbaric Oxygen Therapy for Diabetic Foot Ulcer: An Economic Analysis. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2007.
    1. Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2004. p. CD004123.
    1. Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg. 2005;92(1):24–32. doi: 10.1002/bjs.4863.
    1. Wang C, Schwaitzberg S, Berliner E, Zarin DA, Lau J. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg. 2003;138(3):272–9. doi: 10.1001/archsurg.138.3.272.
    1. Wagner FW Jr. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle. 1981;2(2):64–122.
    1. Borun Center for Gerontological Research. Pressure Ulcer Prevention Training Module. Anna and Harry Borun Center for Gerontological Research. 2004.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010;152(11):726–32.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться