MIST Therapy's Effectiveness in Wound Bed Preparation and Role of Bacterial Biofilm in Chronic, Non-healing Wounds

The trial is designed as an investigator-initiated prospective, randomized, controlled single blinded study, at a single study center, of persons presenting with a chronic, non-healing wound the knee with a potential for rapid deterioration, leading to limb loss. Chronic wounds defined as, having been present longer than 30 days and have failed to demonstrate greater than about a 50% reduction in surface area in the previous 30 days despite the administration of appropriate and standard wound care as well as cases presenting with acute gangrene or massive tissue loss that do not meet the 30 day criteria will be included. All wounds must be at least 5 cm2. A SOC Doppler assessment will be performed to ensure that the wound is adequately vascularized.

For subjects who present with multiple chronic, non-healing wounds, only the largest wound meeting the entrance criteria will be enrolled in the study. This will be referred to as the patient's "index wound." Once a wound is designated as the "index wound," that wound will remain the index wound for the duration of the patient's study participation.

Adult patients with ESRD and who have a chronic, non-healing wound consenting to the study will be screened for eligibility and if subjects meet all the inclusion and none of the exclusion criteria, they will be enrolled for study participation. Enrolled patients will then be randomized to receive one of two treatment courses: a) MIST Therapy in conjunction with Standard of Care (SOC) (treatment group) or, b) SOC only using a Sham device (control group). The Sham device is a nebulizer compressor designed to deliver a continuous saline mist to a MIST Therapy System, but without the ultrasound waves. Both groups will have a primary closure (ie. split thickness skin graft or delayed primary closure) as part of the eventual treatment plan. Both groups will undergo up to 5 SOC surgical debridements in the OR setting, with each debridement immediately followed by the subject's assigned study treatment.

Prior to initiating the assigned study treatment, a randomized patient will be required to undergo a Baseline Evaluation. The Baseline Evaluation will include: wound area measurement, wound bed evaluation, and digital photograph. Following the Baseline Evaluation, a study patient will undergo surgical debridement of the index wound in the operating room setting. During this time, a tissue sample will be obtained prior to debridement in both study groups. A second tissue sample will be obtained from both study groups immediately following debridement (either SOC debridement or MIST therapy, depending on which group the patient was randomized into). These tissue samples will be utilized to assess the presence of biofilm in the wound prior to and following the assigned study treatment. A tissue sample will be taken in the form of a 2mm punch biopsy that will be obtained from the center of the wound as well as the wound margin in both study groups prior to debridement and immediately following debridement (either SOC debridement or MIST therapy, depending on which group the patient was randomized into). Along with SOC wound cultures, a swab of the wound will be taken before and after the treatment at the first OR visit and be sent to the Georgetown University lab for quantitative analysis of the bacteria present.

Following the Baseline evaluation and surgical debridement, study subjects will undergo up to 4 subsequent Interim Study Evaluations. The Interim Study Evaluations will include a wound assessment, wound measurements, digital photographs, and an adverse event assessment, and will be conducted at a frequency determined appropriate by the Principal Investigator until the wound bed appears appropriate for primary closure. As part of each Interim Study Evaluation, study subjects will undergo a subsequent surgical debridement in the OR setting, immediately followed by the assigned study treatment, (i.e., sham device with saline rinse or MIST therapy). Prior to each subsequent surgical debridement, a SOC wound culture and quantitative wound culture will be obtained for analysis.

Final tissue biopsies, from the wound center and wound margin, will be obtained prior to the primary closure procedure. Following definitive wound closure procedure, split thickness skin graft or delayed primary wound closure, the subject will undergo Bi-Monthly Wound Assessment, being followed for a maximum of 20 weeks from the date of his/her first surgical debridement. A Bi-Monthly Wound Assessment will include an assessment of maintained wound closure and an adverse event assessment.

SOC post-operative dressings may include Moist Wound Therapy and the use of Negative Pressure Wound Therapy. NOTE: No impregnated dressings will be allowed during the study period. No topical antibiotics or antibiotic dressings, topical antiseptics (silver, iodine, etc.), or antimicrobials will be allowed. The use of EMLA Cream is not allowed.