In this prospective, randomized, multicenter, open-label, parallel group study conducted with 29 subjects from 8 clinical study sites, study candidates with open chronic wounds of the foot were assessed for eligibility as listed in Table 1. The study period consisted of a 2-week screening period, the baseline visit with randomization of qualified subjects, and a treatment period of 6 weeks, a timeframe modeled after Zelen et al.6,8 During each weekly study visit, the ulcer bed was assessed for epithelialization, granulation, and necrosis as well as any clinical signs of infection, the ulcers were photographed and measured, and all adverse events collected. Data were recorded in a web-based electronic case report form and stored in an electronic database used to perform all the statistical assessments (X Trials Research, Somerset, NJ).
Standard of care for all subjects. All subjects enrolled in this study received SOC throughout the trial, which included debridement of necrotic/nonviable tissue and hemostasis (no silver nitrate sticks or styptic pencils were permitted), moist wound dressings, offloading where appropriate with a DH Walker boot (Össur, Foothill Ranch, CA), and infection surveillance and management. All subjects returned to the clinic every week for dressing changes, wound inspection, debridement, and application of DAMA (as per randomization allocation and per the investigator’s discretion).
Screening period. After eligible candidates provided informed consent, target DFUs were cleaned, debrided, photographed, and measured. Candidates were provided with dressing materials and an offloading device and were instructed to return to the clinic in 2 weeks for assessment. If, upon return, the target DFU had closed less than 30% in area during the 2-week screening period, the subject was randomized (1:1) to 1 of 2 treatment groups: DAMA+SOC or SOC alone. Randomization occurred through a module within the electronic case report form and was stratified by ulcer area (1 cm2-10 cm2 vs 10.1 cm2-25 cm2) and clinical site.
Standard of care alone cohort. For subjects randomized to receive SOC alone, in addition to the SOC outlined above in “Standard of care for all subjects,” XTRASORB Foam Non-Adhesive Dressing (Derma Sciences, Princeton, NJ) was applied to the ulcer after debridement (when necessary) and, once hemostasis was achieved, the wound was wrapped with Duform Synthetic Conforming Bandage (Derma Sciences, Princeton, NJ) and lightly secured. A compression dressing of Duban Cohesive Bandage (Derma Sciences, Princeton, NJ) wrap was applied as a cover dressing.
Dehydrated amniotic membrane allograft + standard of care cohort. For subjects randomized to receive DAMA in addition to SOC as outlined above (n = 15), the ulcer was debrided, hemostasis achieved, and DAMA that had been cut to fit the wound bed was applied. The ulcer was dressed with Adaptic (Systagenix, Gatwick, UK) and covered with the foam nonadhesive dressing. The area was wrapped with the conforming bandage and lightly secured. A compression dressing of the cohesive bandage wrap was applied as a cover dressing. Subjects were instructed not to change their dressings. Reapplication of DAMA could occur as often as once per week, based upon the physician’s judgment.
Primary endpoint and statistical analyses. The primary endpoint of the study was the proportion of subjects with complete wound closure prior to or on week 6 after initiation of treatment. Complete wound closure was defined as 100% complete skin reepithelialization without drainage or dressing requirements.
The proportion of subjects with complete wound closure at or before 6 weeks was analyzed using Fisher’s Exact test, and Kaplan-Meier methodology was used for time-to-event analyses. Data were, at a minimum, summarized using mean, standard deviation, medians, and/or proportions, as appropriate.
The protocol, informed consent form, and any appropriate related documents were reviewed and approved by the following Institutional Review Boards (IRB): Western IRB, Beth Israel Deaconess-Plymouth IRB, Duke University Health System IRB, and Wayne Memorial Hospital IRB. The study was conducted in adherence to Good Clinical Practice guidelines as required by the Principles of the World Medical Association Declaration of Helsinki 2013; the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E6 Guideline for Good Manufacturing Practice (Committee for Proprietary Medicinal Products/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products; and the US Food and Drug Administration CFR Title 21 regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and IRB regulations and applicable sections of US 21 CFR Parts 312 and 1271.