Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Dermagraft applied weekly promoted healing in diabetic foot ulcers

ACP J Club. 1996 Sept-Oct;125:42. doi:10.7326/ACPJC-1996-125-2-042


Source Citation

Gentzkow GD, Iwasaki SD, Hershon KS, et al. Use of Dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care. 1996 Apr;19:350-4. [PubMed ID: 8729158]


Abstract

Objective

To determine the effectiveness of Dermagraft (Advanced Tissue Sciences, La Jolla, California), a cultured human dermis, in the healing of diabetic foot ulcers.

Design

12-week randomized controlled trial.

Setting

5 institutions in the United States.

Patients

50 patients (mean age 61 y, 70% men) who had non-insulin-dependent diabetes mellitus (15 patients) or insulin-dependent diabetes mellitus (35 patients) under reasonable control. Inclusion criteria were ≤ 1 hospitalization in the previous 6 months for hyperglycemia, hypoglycemia, or ketoacidosis; a full-thickness (> 1 cm2) plantar foot ulcer; a wound bed free of necrotic debris and infection and suitable for skin graft; and adequate circulation in the foot. Exclusion criteria were nondiabetic ulcers, medications adverse to healing, or pregnancy. All patients completed the 12-week study period.

Intervention

All patients received therapeutic shoes and were advised to avoid bearing weight on the treated foot; ulcers were sharply debrided. Patients were allocated to 1 of 4 groups: Group A received 1 piece of Dermagraft per week for 8 weeks plus standard care (n = 12), group B received 2 pieces every other week for 8 weeks plus standard care (n = 14), group C received 1 piece every other week for 8 weeks plus standard care (n = 11), and group D received standard care for 12 weeks (n = 13).

Main outcome measures

Rates of complete and 50% wound closure.

Main results

Analysis was by intention to treat. Complete closure by week 12 was achieved by more patients in group A than in groups B, C, and D (50%, 21%, 18%, and 8%, respectively; P = 0.03 for group A compared with group D) (Table). The percentages of patients who achieved 50% wound closure in groups A, B, C, and D were 75%, 50%, 18%, and 23%, respectively; P = 0.02 for group A compared with group D. No adverse effects occurred with Dermagraft.

Conclusion

Dermagraft, a cultured human dermis, applied for 8 weeks to diabetic foot ulcers was more effective than standard care in achieving wound closure.

Source of funding: Advanced Tissue Sciences, Inc.

For article reprint: Dr. G.D. Gentzkow, Advanced Tissue Sciences, Inc., 10933 North Torrey Pines Road, La Jolla, CA 92037, USA. FAX 858-713-7400.


Table. Dermagraft vs standard care in diabetic foot ulcers*

Outcomes at 12 wk Dermagraft Standard care RBI (95% CI) NNT (CI)
Complete wound closure 50% 8% 550% (275 to 3747) 2 (1 to 13)
50% wound closure 75% 23% 225% (30 to 850) 2 (1 to 8)

*Abbreviations defined in Glossary. RBI, NNT, and CI calculated from data in article.


Updated Commentary

The study by Gentzkow and colleagues on the use of Dermagraft addresses the recalcitrance of diabetic foot ulcers to heal quickly and remain closed. Clinical protocols subsequent to this pilot study (1, 2) have substantiated the efficacy of this novel approach for the healing of diabetic foot wounds.

The pilot data reported and the follow-up studies showed improvement in healing rates, time to healing, and reduction in ulcer volume and surface area. The methodology in each study was complete with the exception of quantification of neuropathy status and biomechanical parameters. Patients were asked in each case to refrain from weight bearing on the treated foot and were provided special shoes for pressure reduction. More specific information on these 2 elements of the study would have provided readers with a more exacting perspective on the possible confounding effects these 2 risk factors surely contribute to the cause of a diabetic foot ulcer.

The cause of diabetic foot ulcers is an amalgam of programs with glycemic control, vascularity, neurologic integrity, and the biomechanics of gait. Treatment decisions aim to forestall the occurrence of limb loss. Epidemiologic studies are beginning to map the interactive nature of diabetic foot ulceration and limb loss (3), but much remains to be learned. Mechanical stress and neuropathy are receiving increased attention as the precipitating factors in the onset of ulceration (4). Clinical studies suggest that Dermagraft will become an important adjunct in the care of diabetic ulceration. Nevertheless, more studies are needed to further define the interactive effects of abnormal foot pressure and neurological status.

Marvin H. Waldman, DPM, MPH, MS
Department of Veterans Affairs Medical CenterDetroit, Michigan, USA


References

1. Pollak RA, Edington E, Jensen JL, Kroeker RD, Gentzkow GD. A human dermal replacement for the treatment of diabetic foot ulcers. Wounds: a compendium of clinical research and practice. 1997;9:175-83.

2. Genzkow GD, Jensen JL, Pollak RA, et al. Improved healing of diabetic foot ulcers after grafting with a living human dermal replacement. Wounds 1999;11:77-84.

3. Reiber GE. Who is at risk of limb loss and what to do about it. J Rehabil Res Dev 1994;31:357-62.

4. Caputo GM, Cavanaugh PR, Ulbrecht JS, Gibbons GW, Karchmer AW. Assessment and management of foot disease in patients with diabetes. N Engl J Med 1994;331:854-60.