Evaluation of Safety and Efficacy of Barrier Foam Dressing in Patients with Exuding Wounds

Objective : The study was conducted to evaluate the safety, efficacy and tolerability of Barrier Foam Dressing (BFD) combined with ammonium Polyquaternary compound-poly(DADMAC) with regard to effect on wound characteristics i.e., size, discharge, granulation; extent of dressing breakthrough in exuding wounds, pain and time to wound closure by epithelization or readiness for secondary suturing or skin grafting. Material and Methods : The study was an open labeled single center trial of 30 patients with wound or wounds of different etiologies. The patients satisfying inclusion and exclusion criteria as specified in the protocol approved by the Ethical Committee, were enrolled. The wound was evaluated on the basis of size, discharge and granulation at baseline and on every 8th day along with wound photograph till the end point. Microbial analysis of the wound swab and pain score (using Visual Analog Scale - VAS) was recorded at baseline and at the end point of study. Improvement in wound healing was observed by contraction of wound, reduction in exudate, wound debridement and as wound epithelisation, or granulation tissue formation that makes the wound ready to receive a skin graft. Results : BFD was observed to have good ability to absorb wound exudate, help separation of necrotic tissue making debridement easier. Minimal adherence was noticed while removing the dressing. There was no need of any topical antimicrobial along with this dressing. Biochemical and microbiological variables also exhibited the safety and efficacy of this dressing. Its application on skin surface was well tolerated without side effects or local reaction by all except one of the patients. Conclusion : The BFD can be used as a primary dressing for various types of wounds and has favorable influence on wound healing process with good tolerance. Dressing in Patients with Exuding Wounds.

Southern India was found to be 41% [8]. Barrier wound dressings such as foam and gauze are the most commonly used dressings for the prevention of cross contamination and to provide the proper wound healing environment. In India many types of wound dressings are available for example traditional wound dressing (such as gauze, film, bandages, lint), modern wound dressing (including film, foam, hydro gel, hydrocolloids), semi-permeable film dressing, semi-permeable foam dressing, Alginate dressing, Bioactive wound dressings, Tissue engineered skin substitutes, Medicated dressings, Composite dressing [9]. The dressings are either without any antimicrobial or with embedded antimicrobial that forms an active layer between wound and dressing. In these drug eluting dressings, the antimicrobial leaches out of the dressing and into the wound environment.
Barrier Foam Dressing (BFD) is based on the patented NIMBUS ® Technology. BFD is a highly absorbent polyurethane foam specially treated with quaternary ammonium compound poly(DADMAC)). It has long chain polymers (molecular weights of greater than 100,000 Da) with high densities of quaternary amines poly(DADMAC) attached to its surface so that it does not permit leaching of polymer from the dressing into the wound.
Such polymeric quaternary amines have shown to play a vital role as a surface-active agent [10]. The current study aims to evaluate the efficacy, tolerability and safety of BFD in the management of exuding wounds and ulcers.

Study Design
An open labeled study was conducted to evaluate the efficacy, tolerability and safety of BFD in the treatment of exuding wounds and ulcers. Approval was obtained from Independent Ethics Committee (Intersystem BioMedica Ethics Committee, Mumbai, India) before study initiation and was registered with CTRI (CTRI/2012/09/002996). Informed consent was obtained from the patients either examined or admitted at Joy Hospital, Chembur, Mumbai, India before screening and enrollment in the trial.

Primary Outcomes:
The primary objective of this study was to evaluate BFD with regard to: Effect on wound characteristics i.e., size, discharge, granulation, incidence of breakthrough in exuding wounds and microbiology of wound. The end point was assessed as the time to wound closure by epithelization or readiness for secondary suturing or split thickness skin grafting (STSG).

Statistical Analysis:
The test used to calculate statistical analysis was students t-test by using Graph pad prism 5.

Methodology
In this open labeled trial 30 eligible patients were subjected to laboratory screening tests for inclusion after obtaining the written informed consent. Patients meeting the inclusion criteria were enrolled in the study. Detailed case history was recorded.
This included medical history, physical examination, vital signs and medication history. ABI was noted along with the physical examination. Swab for microbial analysis (for Staphylococcus aureas, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa) was obtained. One clinical photograph of the wound site was taken at enrollment. In addition, a regional photograph was also taken that indicated the location of the ulcer on the body. The wound was evaluated for size, discharge, granulation and peri wound skin status, and a wound size tracing was made. Surgical wound debridement was performed as appropriate before enrollment.
Pain score was evaluated based on Visual Analog Scale (VAS) during every visit. Clinical assessment for pain, tenderness, erythema, and edema was done. During the intermediate visits (every alternate day e.g., day 2, day 4…) the dressing was changed. The breakthrough i.e., permeation of discharge through the dressing was evaluated as complete, incomplete, and partial followed by physical examination along with vital signs and medication history.
Surgical debridement was carried out if required. During the weekly visits (day 8, day 16, etc. ± 1 day) the same protocol as at intermediate visits was implemented. One photograph of the wound was taken before debridement if debridement was needed.
Wound size was traced at each weekly visit. Viridis Biopharma Pvt.
Ltd. supplied BFD (size of 10 x10 cm) under licensing from Quick-Med Technologies, Inc. packed in alu-pet. In all the subjects, the BFD was removed every alternate day. The end point was defined as the day the wound was epithelised or was ready for secondary suturing or STSG. At the end point all the procedures performed during weekly visits were repeated. Extent of reduction in wound size was calculated. The wound care protocol followed for all the wounds was uniform. The steps were: Wound cleaning with saline, Debridement if needed after photograph, Application of BFD cut to size, Secondary dressing of sterile gamjee-single pad and fixation of dressing with Tape or bandage.

Results
Out of the 30 screened subjects, 1 was screen failure (individuals who undergo screening but are not enrolled in a clinical trial). Out of 29 enrolled patients 5 were females. Three patients had to be excluded from the analysis due to the reasons detailed below. Hence 26 out of 29 enrolled patients have been considered for analysis. Table 1   The reasons for declaring failure and hence trial termination after more than 3 visits was decided in 3 patients for following reasons       The average reduction in wound size at end point was 60 % in CSSTI while it was observed to be 38 % in patients with diabetic foot ulcer ( Table 2). The average reduction in wound size at end point was 60 % in CSSTI while it was observed to be 38 % in patients with diabetic foot ulcer which was statistically significant (Table 2). Maximum wound size reduction was observed to be 98 % in a sacral bed sore. Table 3

METHOD:
Specimen received in a sterile container was cultured on blood, MacConkey's & specialized media.

COMMON ORGANISMS ISOLATED:
(At the end of 24 hours of incubation at 370C)

METHOD:
Specimen received in a sterile container was cultured on blood, MacConkey's & specialized media.

SMEAR EXAMINATION:
Gram's Stain: No or Occasional Gram-negative bacilli detected

COMMON ORGANISMS ISOLATED:
(At the end of 24 hours of incubation at 370C)

Discussion
The common problem with majority of currently available dressings is they cannot be used as a primary dressing. They need application of one of the topical antimicrobial agent or hydro gels beneath the primary dressing. It is now known that most of the primary antimicrobial impregnated dressings which are applied with the secondary barrier dressing loose their effectiveness over a period due to leaching and hence make the dressing ineffective, wound healing more difficult and prolonged. The persistent inflammatory response contributes to delayed healing of wound and increase in bioburden [11][12][13][14]. Commonly used antimicrobial agents have been found to be ineffective in reducing this bioburden [15][16][17]. Hence there is a need of effective antimicrobial barrier dressing which can be used as a Primary dressing but will not leach out of the dressing. Gauze Woven dressings are the most widely used wound dressing primarily due to their high absorptive capacity, easy availability, and low cost. However, due to their woven structure as well as absorptive nature it is possible for microorganisms, more importantly nosocomial pathogens, to utilize the gauze characteristics and infect wounds. Hence it is necessary to block such bacterial biofilm formation in these wounds [18][19][20][21]. It has also been shown that these dressings can shed bacteria into the wound and can play a role in cross contamination [19].
Aerosolization of the bacteria on such dressings can contaminate the wards, operating theatres, and burn unit thus playing a role in spreading nosocomial infections [20,21]. So, there is a need for dressing that can prevent or minimize this possibility.
The caregiver also needs to consider adherence of the dressing Various studies conducted on BFD demonstrated the inhibition of bacterial growth under the dressing. In a study by Trans PL, et al. [22], pDADMAC-PU dressing produced more than 8 log reduction in biofilm formation by pathogens suggesting pDADMAC-PU to be an effective wound dressing that inhibits the growth of wound pathogens both within the wound and in the wound dressing [22]. Similar results were observed in a in vivo mouse model [23].
Another study conducted by Mikhaylova et al. [24]

Conclusion
On completion of the study, the Investigators are of the opinion that BFD is eminently suitable for exuding wounds and ulcers considering its safety, tolerability, and efficacy. It is very convenient to use and it is easy to train the patient or relative to use it at home for wound care. This is a very valuable quality in view of large number of patients especially with diabetic foot and CSSTIs in India and the long duration needed for wound healing in these patients. However controlled studies in larger population will help in comparing efficacy and probably establishing superiority of BFD for wound management in comparison with presently available drug eluting dressings.

Declaration of Interest
This study was sponsored by Viridis BioPharma Pvt. Ltd., Mumbai, India by providing the dressing material including the dressing under trial, proformas, wound size measurement sheets.