Comparative Effectiveness of Two Collagen-containing Dressings: Oxidized Regenerated Cellulose (ORC)/Collagen/Silver-ORC Dressing Versus Ovine Collagen Extracellular Matrix

Introduction. Chronic wounds are characterized by impaired tissue physiology that stalls healing. The prevalence of wound chronicity presents challenges in wound management and health care cost-containment. Objective. This comparative effectiveness study evaluates the value proposition of 2 collagen-containing wound dressings — oxidized regenerated cellulose (ORC)/collagen/silver-ORC dressing and ovine collagen extracellular matrix (ECM) — in matched cohorts of patients undergoing treatment for diabetic foot ulcers (DFUs). Materials and Methods. Data extracted from the US Wound Registry identified DFUs treated with either dressing and included wounds with complete data records (n = 3230). Thirty-seven variables were considered in propensity score matching to develop a case-matched cohort of 844 DFUs (n = 422 DFUs/group). Results. The ORC/collagen/silver-ORC dressing group yielded a significantly higher percentage of DFUs that healed or improved (82% vs. 74.6%; P = .0096). The ovine collagen ECM dressing group yielded a significantly higher percentage of DFUs that worsened (15.2% vs. 23.9%; P = .0013). The ORC/collagen/silver-ORC dressing group demonstrated a higher percentage of DFUs that attained 75% to 100% granulation at zero depth at 4, 8, 12, and 16 weeks. Median time to 75% to 100% granulation was 42 days for the ORC/collagen/silver-ORC dressing group versus 60 days for the ovine collagen ECM dressing group (P = .0109). Conclusions. According to this comparative effectiveness study using real world data, ORC/collagen/silver-ORC dressing appears to afford improved healing and reduced time to granulation relative to ovine collagen ECM dressing.

Chronic wounds are characterized by impaired tissue physiology that stalls healing.¹ The prevalence of wound chronicity presents various challenges in wound management and health care cost-containment. Patients with diabetic foot ulcers (DFUs) have more hospital days, emergency room visits, home health care, and outpatient/physician visits, and cost an additional $9 billion to $13 billion to private and public payers when compared with matched cohorts.² Here, the authors present a comparative effectiveness study to evaluate the value proposition of 2 collagen-containing wound dressings — oxidized regenerated cellulose (ORC)/collagen/silver-ORC dressing (PROMOGRAN PRISMA Matrix; Systagenix Wound Management Ltd., Gargrave, UK) and ovine collagen extracellular matrix (ECM; ENDOFORM Natural Dermal Template; Aroa Biosurgery Limited, Auckland, New Zealand) — in matched cohorts of patients undergoing treatment for DFUs. 

Wound Registry [USWR]) was used to identify DFUs with complete data records that were treated with either ORC/collagen/silver-ORC or ovine collagen ECM. Propensity score matching across 37 variables was performed to construct a case-matched cohort. Standardized mean differences were used to compare balance between ORC/collagen/silver-ORC and ovine collagen ECM. Two-sample t tests were used for continuous variables, and chi-squared or Fisher’s exact test was used for categorical variables to compare ORC/collagen/silver-ORC and ovine collagen ECM post-matching.

Data extracted from the USWR identified DFUs (n = 3230) treated with either ovine collagen ECM (n = 422) or ORC/collagen/silver-ORC (n = 2808). Propensity score matching generated a case-matched cohort of 844 DFUs (n = 422 DFUs/product group). There were no statistical differences in the patient demographics and select comorbidities (Table 1), ulcer demographics (Table 2), or in the distribution of additional treatment types (Table 3) between cohorts. In both cohorts, the median initial area of the DFU was 1.5 cm² and median time to the first collagen dressing application was 14 days for both cohorts. The ORC/collagen/silver-ORC dressing group yielded a significantly higher percentage of DFUs that healed or improved (82% vs. 74.6%; P = .0096) (Figure 1). The ovine collagen ECM dressing group yielded a significantly higher percentage of patients with DFUs that worsened (15.2% vs. 23.9%; P = .0013) (Figure 2). The ORC/collagen/silver-ORC dressing group demonstrated a higher percentage of DFUs that attained 75% to 100% granulation at zero depth at 4, 8, 12, and 16 weeks, with significantly higher rates at 12 weeks (59.7% vs. 50.2%; P = .0225) and 16 weeks (63.6% vs. 54.8%; P = .0325) (Figure 3). In a time-to-event analysis, median time to 75% to 100% granulation was 42 days for the ORC/collagen/silver-ORC dressing group versus 60 days for the ovine collagen ECM dressing group (P = .0109).

Diabetic foot ulcers are a common complication of diabetes. It is estimated that up to 4% of those with diabetes suffer from a DFU annually, and about 25% of patients with diabetes will experience a DFU during their lifetime.³ 

A 2014 study by Rice et al² noted that patients with DFUs increased health care utilization, resulting in those patients having $11 710 in incremental health care costs for Medicare and $16 833 for private insurance. This results in a burden on public and private payers, ranging from $9 billion to $13 billion in additional costs.² In addition, annual Medicare spending for DFUs has an estimated range of $6.2 billion to $18.7 billion.⁴ 

Early use of ORC/collagen/silver-ORC may assist in optimizing the wound environment, which may help to promote granulation tissue formation.¹ Ulrich et al⁵ evaluated the effect of ORC/collagen/silver-ORC on proteases in DFUs in which 22 patients receiving ORC/collagen/silver-ORC were compared with 10 patients receiving standard hydrocolloid dressings. The study found DFUs treated with ORC/collagen/silver-ORC showed a significant reduction in the levels of all evaluated proteases as well as a significantly greater reduction in ulcer size at 14 and 28 days.⁵ 

In a randomized controlled trial,⁶ 24 patients with a DFU receiving ORC/collagen/silver-ORC were compared with 15 patients with a DFU receiving standard of care (SOC). At weeks 4, 8, and 10, significantly more DFUs in the ORC/collagen/silver-ORC cohort had at least 50% ulcer area reduction compared with the SOC group. At the end of the study, 91% of the DFUs treated with ORC/collagen/silver-ORC healed or showed an ulcer area reduction of at least 50% compared with 69% of DFUs enrolled in the SOC cohort. At week 14, 52% of DFUs in the ORC/collagen/silver-ORC cohort healed versus 31% of DFUs in the control group.⁶ In the present study, a higher proportion of ulcers in the ORC/collagen/silver-ORC cohort attained 75% to 100% granulation at 12 weeks (59.7% vs. 50.2%) and at 16 weeks (63.6% vs. 54.8%) relative to the control collagen dressing cohort. These data report 74.6% (315/422) versus 82.0% (346/422) of DFUs healed or improved. 

One limitation is that the matching and analyses were done at the level of the wound. Many of the patients represented within the dataset have multiple wounds. Current literature in this area of research generally performs analyses on the wound level and does not consider the patient within these models. Therefore, treating wounds as independent in the analyses may be problematic if there are any within patient correlations. Secondly, the present analysis did not adjust for covariates. Propensity score matching merely generated a set for analysis that reflected patient balance based upon background covariates. In order to increase precision while estimating treatment effects, adjusted models would need to be fit.

According to the results of this comparative effectiveness study using real world data, ORC/collagen/silver-ORC dressing appears to afford improved healing rates and reduced time to granulation in comparison to ovine collagen ECM dressing.

Authors: Leah Griffin, MS¹; Marissa J. Carter, PhD, MA, MAPWCA²; Ralph D’Agostino, Jr, PhD³; and Lucy D’Agostino McGowan, PhD⁴

Affiliations: ¹KCI, San Antonio, TX; ²Strategic Solutions, Inc, Cody, WY; ³Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC; and ⁴Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Correspondence: Leah Griffin, MS, KCI, 12930 W Interstate 10, San Antonio, TX 78249; Leah.Griffin@Acelity.com

Disclosure: Financial support for this research was provided by KCI, San Antonio, TX. Willie M. Heard III, PhD, (KCI) provided medical writing support.