Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo‐controlled trial

Abstract

Several small studies have indicated that the systemic administration of pentoxifylline may accelerate healing of venous leg ulcers. The goal of this study was to further evaluate these findings in a larger scale placebo controlled trial and to explore the effect of the dose of pentoxifylline on healing. The study used a prospective, randomized, double-blind, parallel group placebo controlled design in a multicenter outpatient setting. Patients with one or more venous ulcer were enrolled, with all patients receiving standardized compression bandaging for treatment for their ulcers. Patients were also randomized to receive either pentoxifylline 400 mg, pentoxifylline 800 mg (two 400 mg tablets), or placebo tablets three times a day for up to 24 weeks. The main outcome measure was time to complete healing of all leg ulcers, using life table analysis. The study was completed as planned in 131 patients. Patients receiving 800 mg three times a day of pentoxifylline healed faster than placebo (p = 0.043, Wilcoxon test). The median time to complete healing was 100, 83, and 71 days for placebo, pentoxifylline 400 mg, and pentoxifylline 800 mg three times a day, respectively. Over half of all patients were ulcer free at week 16 (placebo) and at week 12 in both pentoxifylline groups. Whereas the placebo group had only achieved complete healing in half of the cases by week 16, all of the subjects remaining in the group receiving the high dose of pentoxifylline had healed completely. Treatment with pentoxifylline was well tolerated with similar drop-out rates in all three treatment groups. Complete wound closure occurred at least 4 weeks earlier in the majority of patients treated with pentoxifylline by comparison to placebo. A higher dose of pentoxifylline (800 mg three times a day) was more effective than the lower dose. We conclude that pentoxifylline is effective in accelerating healing of leg ulcers.

Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy

“…It has been demonstrated that pentoxifylline, an oral methylated xanthine derivative, improves blood flow by decreasing blood viscosity and may be effective in accelerating healing of venous leg ulcers. 80 Faster healing with combined pentoxifylline and compression therapy was shown in a 2014 Cochrane systematic review.…”

Treatment of venous ulcers

“…Most medications employed as adjuvant therapy possess mechanisms of action that may ameliorate factors identified as abnormal and related to the pathophysiology of venous ulceration such as abnormal fibrinolysis [4]. • Pentoxifylline, a methylxantine derivative, is a promising agent in the treatment of venous ulcers, due to its fibrinolytic properties, its ability to reduce leukocyte adhesion to the vascular endothelium, and its antithrombotic effects [4,10]. In the past, the indication for the use of pentoxifylline has been controversial.…”

“…However, it has currently been reconsidered as an adjuvant agent to be used in addition to limb compression therapy, as it is suggested by a recent review of five studies performed by the Cochrane Collaboration [4,11]. Additionally, although several small studies have suggested a beneficial effect of the regimen of 400 mg of pentoxyphylline three times a day, Falanga et al [10] have demonstrated a greater statistically significant effect on time to complete wound healing when 800 mg was administered three times daily as opposed to 400 mg and placebo [4]. Contraindications to its use include allergy or tolerance to methylxanthines.…”

Venöz Ülser Tedavisinde Venoaktif İlaçlar

“…Previously in venous ulcer therapy venoactive medications such as pentoxifylline, prostaglandin, acetylsalicylic acid and sulodexide had been used. (10)(11)(12)(13)(14)(15)(16)(17). In this document, we discuss the scientific evidence on efficacy of venoactive drug therapy on treatment of venous ulcer.…”

“…Hyperglycaemia and consumption of glucose within the cell cause changes in intracellular and extracellular concentrations of Na + ions directly and Ca ++ ions indirectly (7), and hence it may be implied that the Na + -K + ATPase and Ca ++ ATPase enzyme activities could be affected by these changes. In previous studies, it has been indicated that impaired sodium transport and Na + -K + ATPase activity in the erythrocyte membrane possibly have prominent roles in the pathophysiology of chronic complications of diabetes mellitus (8)(9)(10)(11). Furthermore, it has been reported in several studies conducted in vivo and in vitro conditions that there are changes in the Na + -K + ATPase and Ca…”