Evidence Corner
- Thu, 9/4/08 - 11:52am
- 0 Comments
- 2200 reads
Dear Readers:
Healing the foot or leg ulcer (DU) of a patient with diabetes lowers his or her risk of lower-extremity amputation, a frequent precursor of morbidity and mortality.1 Evidence-based management requires
consistent offloading or protection of the DU site, metabolic control, and a moist wound environment1,2 in addition to careful debridement.2,3 Clinicians may choose from a variety of topical modalities. Despite evidence of improved healing relative to placebo or gauze5–7 none of these seem widely accepted. The search for improved topical DU management continues. This month’s Evidence Corner describes recent research on further options to manage these challenging wounds—a thrombin peptide and a silver dressing.
Laura Bolton, PhD, FAPWCA
Adjunct Associate Professor
Department of Surgery, UMDNJ
WOUNDS Editorial Advisory Board Member and Department Editor
Thrombin Peptide Stimulates Diabetic Ulcer Repair
Reference: Fife C, Mader JT, Stone J, et al. Thrombin peptide Chrysalin® stimulates healing of diabetic foot ulcers in a placebo-controlled phase I/II study. Wound Repair Regen. 2007;15(1):23–24.
Rationale: Diabetic ulcers pose a significant healthcare challenge. Advanced therapeutic options for DU, such as bilayered skin equivalents or growth factors cleared by the FDA, do not appear to be widely accepted as standards of care.
Objective: Explore pilot clinical efficacy and safety of a thrombin peptide topically applied to noninfected chronic DUs on the leg, ankle or foot.
Methods: A 4-center, prospective, randomized, double-blind, placebo-controlled pilot study enrolled 60 noninfected patients with metabolically controlled diabetes, a Wagner Grade I-III (without eroded tendon or bone) below-the-knee DU 1–7 cm in diameter, and a wound TcPO2 > 20 mmHg. The study DU in 20 patients in each treatment group received sharp debridement as needed, saline irrigation, and 100 µL of saline containing either 0 (placebo), 1, or 10 µg of the thrombin peptide topically applied twice weekly under a foam dressing for up to 20 weeks. A walker boot with evidence of efficacy was used to offload pressure-bearing ulcers, except for a few patients who used crutches or wheelchairs. Subjects were removed from the study and were deemed “nonhealed” if a clinical infection developed or the study DU condition significantly worsened. The primary healing efficacy endpoint was the percentage of wounds completely closed during 20 weeks, with secondary measures of time to 80% or 100% closure. The primary safety outcomes included adverse events (eg, erythema, edema, pain, and overall condition) assessed biweekly. Hematological assays, wound cultures, and radiographs were obtained and analyzed at weeks 5, 10, 15, and 20.
Results: There were no statistically significant effects of the thrombin peptide on safety or primary or secondary healing end points, with or without excluding patients inadvertently enrolled whose ulcers did not meet the enrollment criteria. Subjects and ulcers were initially comparable in all 3 groups, including subsets of < 10/group in a post-hoc analysis of study foot ulcers (DFU) in which the thrombin peptide increased the percent healed and decreased median healing time (P < 0.05).
Conclusion: Significant data obtained in this pilot study suggest that topical application of the thrombin peptide may benefit DFUs.
Silver Dressing Reduces Diabetic Foot Ulcer Depth
1. American Diabetes Association. Consensus development conference on diabetic foot wound care. Diabetes Care. 1999;22(8):1354–1360.
2. Cavorsi J, Vicari F, Wirthlin DJ, et al. Best-practice algorithms for the use of a bilayered living cell therapy (Apligraf) in the treatment of lower-extremity ulcers. Wound Repair Regen. 2006;14(2):102–109.
3. 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(1):61–64.
4. Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. Diabetes Care. 1999;22(5):692–695.
5. Marston WA, Hanft J, Norwood P, Pollak R for the Dermagraft Diabetic Foot Ulcer Study Group. The efficacy and safety of dermagraft in improving the healing of chronic diabetic foot ulcers. Diabetes Care. 2003;26(6):1701–1705.
6. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care. 1998;21(5):822–827.
7. Veves A, Sheehan P, Pham HT; for the Promogran Diabetic Foot Ulcer Study. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg. 2002;137(7):822–827.
