A multicenter, randomized, single‐blind trial comparing the efficacy of viable cryopreserved placental membrane to human fibroblast‐derived dermal substitute for the treatment of chronic diabetic foot ulcers

Abstract

Randomized controlled clinical trials, the gold standard to determine treatment efficacy against control, have demonstrated advantages of skin substitutes for the treatment of chronic diabetic foot ulcers in comparison to standard of care. However, randomized controlled clinical trials comparing efficacy between two or more skin substitutes are very limited. With growing numbers of new skin substitutes, such studies are essential for treatment and policy-making decisions by wound care providers and payers. In this study, we analyzed clinical outcomes and product cost between a viable cryopreserved placental membrane (vCPM) and a human fibroblast-derived dermal substitute (hFDS) for the treatment of chronic diabetic foot ulcers in a prospective, multicenter, single-blind study. The outcomes of 62 patients were analyzed: 31 patients in the vCPM treatment group and 31 patients in the hFDS treatment group. Utilizing a non-inferiority trial design and the established treatment regimen of 8 applications for hFDS, we demonstrated that vCPM was not inferior to hFDS for the proportion of patients achieving complete wound closure (9.68, 90% CI: [10.67, 28.94]). However, preliminary findings show that vCPM may have better outcomes for wounds ≤ 5 cm : 81.3% (13/16) of wounds in the vCPM group vs. 37.5% (6/16) of wounds in the hFDS group reached complete closure at the end of treatment (p = 0.0118). A preliminary product cost analysis for wounds ≤ 5 cm may show significant savings for patients treated with vCPM. Average per-patient costs during the course of treatment were $3,846 and $7,968 (p < 0.0001) for vCPM and hFDS patients, respectively. These results may be used as guidance to wound care providers and payers.

Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update)

“…These interesting early data need confirming in a further independent RCT. A further study designed to show non‐inferiority of a placental product compared with a human fibroblast‐derived dermal substitute was also found, however, the significance of this finding is unclear given the comparator …”

“…The previous review reported a single study of an amniotic membrane wound graft but commented that the study was of high risk of bias and the conclusions marred by the low rate of healing in the comparator group . In the relatively short period of time since that study, interest in this type of therapy has developed rapidly as shown by the number of new placental‐derived products available and the publication of eight RCTs and a cohort registry study …”

“…64 In the relatively short period of time since that study, interest in this type of therapy has developed rapidly as shown by the number of new placental-derived products available and the publication of eight RCTs and a cohort registry study. [64][65][66][67][68][69][70][71][72][73][74] The effect of an amniotic membrane allograft was compared with standard care in a well-designed RCT. 65 The incidence of ulcer closure was greater, as was median time to ulcer closure in those receiving the amniotic membrane allograft.…”

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: a systematic review

“…These interesting early data therefore need confirming in a further blinded RCT. A further study designed to show noninferiority of a placental product compared with a human fibroblast‐derived dermal substitute was also found; however, the significance of this finding is unclear given the comparator …”

“…The previous review reported a single study of a cryopreserved amniotic membrane ulcer graft but commented that the study was at high risk of bias and the conclusions marred by the low rate of healing in the comparator group . In the relatively short period of time since that study, interest in this type of therapy has developed rapidly with the publication of eight RCTs and a cohort registry study …”