Randomised, Double Blind, Multicentre, Placebo Controlled Study of Sulodexide in the Treatment of Venous Leg Ulcers

Summary

Sulodexide, a highly purified glycosaminoglycan, was investigated for treatment of venous leg ulcers. Patients (n = 235) undergoing local treatment including wound care and compression bandaging, were randomised to receive either sulodexide or matching placebo for three months. Primary study endpoint was complete ulcer healing after 2 months; secondary endpoints were ulcer healing at 3 months and the time-course changes of ulcer areas.

The proportion of patients with complete ulcer healing was higher with sulodexide at 2 months (p = 0.018) and 3 months. The “number needed to treat” to obtain one additional patient healed with sulodexide was 7 at 2 months and 5 at 3 months. The changes in ulcer surface area with time were significant for sulodexide only (p = 0.004). Fibrinogen significantly decreased in sulodexide patients (p = 0.006).

In conclusion, sulodexide associated with local treatment proved to be effective and well tolerated in the management of venous leg ulcers.

Keywords

Sulodexide - chronic venous insufficiency - venous leg ulcer - glycosaminoglycans

• References

• 1 Nicolaides AN. Investigation of chronic venous insufficiency: A consensus statement. Circulation 2000; 102: e126-63.
• 2 Kurz X, Kahn SR, Abenhaim L, Clement D, Norgren L, Baccaglini U, Berard A, Cooke JP, Cornu-Thenard A, Depairon M, Dormandy JA, Durand-Zaleski I, Fowkes GR, Lamping DL, Partsch H, Scurr JH, Zuccarelli F. Chronic venous disorders of the leg: epidemiology, outcomes, diagnosis and management. Consensus Statement. Intern Angiol 1999; 18: 83-102.
• 3 Ruckley CV. Socioeconomic impact of chronic venous insufficiency and leg ulcers. Angiology 1997; 48: 67-9.
• 4 Dormandy JA. Pathophysiology of venous leg ulceration – an update. Angiology 1997; 48: 71-5.
• 5 Fletcher A, Cullum N, Sheldon TA. A systemic review of compression treatment for venous leg ulcers. BMJ 1997; 315: 576-80.
• 6 Gallenkemper G, Schultz-Ehrenburg U. Adjuvant systemic drug therapy in venous ulcers. Curr Probl Dermatol 1999; 27: 153-60.
• 7 Ofosu FA. Pharmacological actions of sulodexide. Semin Thromb Hemost 1998; 24: 127-38.
• 8 Harenberg J. Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev 1998; 18: 1-20.
• 9 Ceriello A, Quatraro A, Marchi E, Barbanti M, Giugliano D. Glycosaminoglycans administration decreases high fibrinogen plasma levels in diabetic patients. Diab Nutr Metab 1993; 06: 1-4.
• 10 Milani MR, Busutti L, Breccia A. Pharmacokinetics of sulodexide evaluated from 131I-labelled fast-moving heparin after single intravenous and oral administration on man at different doses. Brit J Clin Res 1992; 03: 161-78.
• 11 Saviano M, Maleti O, Liguori L. Double-blind, double-dummy, randomized, multicentre clinical assessment of the efficacy, tolerability and doseeffect relationship of sulodexide in chronic venous insufficiency. Curr Med Res Opin 1993; 13: 96-108.
• 12 Scondotto G, Aloisi D, Ferrari P, Martini L. Treatment of venous ulcers with sulodexide. Angiology 1999; 50: 883-9.
• 13 Vanscheidt W, Heidrich H, Junger M, Rabe E. Guidelines for testing drugs for chronic venous insufficiency. Vasa 2000; 29: 274-8.
• 14 Guilhou JJ, Dereure O, Marzin L, Ouvry P, Zuccarelli F, Debure C, Van Landuyt H, Gillet-Terver MN, Guillot B, Levesque H, Mignot J, Pillion G, Fevrier B, Dubeaux D. Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology 1997; 48: 77-85.
• 15 Glinski W, Chodynicka B, Roszkiewicz J, Bogdanowski T. The beneficial augmentative effect of micronised purified flavonoid fraction (MPFF) on the healing of leg ulcers: an open, multicentre, controlled, randomised study. Phlebology 1999; 14: 151-7.
• 16 Jull AB, Waters J, Arrol B. Oral pentoxifylline for treatment of venous leg ulcers (Cochrane Review). In: The Cochrane Library. Issue 02 2000. Oxford: Update Software; CD001733.
• 17 Dale JJ, Ruckley CV, Harper DR, Nelson EA, Prescott RJ. Randomised, double blind placebo controlled trial of pentoxifylline in the treatment of venous ulcers. BMJ 1999; 319: 875-8.
• 18 Layton AM, Ibbotson SH, Davies JA, Goodfield MJ. Randomised trial of oral aspirin for chronic venous leg ulcers. Lancet 1994; 344: 164-5.
• 19 Belcaro G, Marelli C. Treatment of venous lipodermatosclerosis and ulceration in venous hypertension by elastic compression and fibrinolytic enhancement with defibrotide. Phlebology 1989; 04: 91-106.
• 20 Rajtar G, Marchi E, De Gaetano G, Cerletti C. Effects of glycosaminoglycans on platelet and leucocyte function: role of N-sulfation. Biochem Pharmacol 1993; 46: 958-60.