Proof of concept study of RECCE®327 topical anti-infective therapy for mild skin and soft tissue diabetes foot infections (DFIs)

The topical "spray-on" formulation of RECCE®327 solution is a pale-yellow colour, has a pH of 7.1 and contains polyacrolein polyethene glycol oligomers 4.76% [polyethylene glycol (PEG) 200 (56.20%), water (39%), the active oligomer (4.76%; 7.80% TM001), acrolein monomer (0.189ppm) and conjugated carbonyls (1.15 ABS @ 230 nm, & 0.75 ANS @ 272nm). The technique for topical delivery of RECCE®327 solution is quick, simple and does not require hospitalisation. It is anticipated that less than 1mL of RECCE®327 solution will be required to saturate the wound bed. The number on mL (to 1 decimal place) will be recorded. We do not envisage that there will be ulcers of significant size requiring the dispensing of >1mL of RECCE®327 solution. The wound will be left open until visibly dry for at least 5 minutes (whichever is first) before it is covered with a standard foam dressing. This is to ensure that there is adequate absorption of the topical preparation into the wound bed and to prevent immediate uptake into dressings. Cohort 1 (16 participants) will receive spray-on RECCE®327 daily over a 14-day study period whilst Cohort 2 (16 participants) will receive spray-on RECCE®327 every two days during a 14-day study period. Appropriate participants will be identified in the High Risk Foot Clinic by the research podiatrist and other members of the study team. This will be their initial appointment or "day 0". Procedures including the removal of dressings, irrigation, debridement, preparation, and application of the topical RECCE®327 and re-dressing will occur and should take approximately 30 minutes. This represents a typical consultation time for HRFS patients, however the number of visits required over the study duration are more than "standard care" (i.e. removal of dressings, wound cleansing, conservative sharps debridement of non-viable wound bed tissue and periwound tissue, appropriate selection of dressings and pressure offloading with chairside devices, prefabricated foot orthoses, post-operative wound shoes, knee-high walkers etc.) The study team will dispense a weeks' supply of RECCE®327 solution in a cooler bag with a temperature tracker on the day of recruitment and day 7 or the midpoint of the study. The amount dispensed will depend on treatment cohort allocation: - Baseline - Daily application cohort: 5x 10mL vials of topical RECCE®327 solution. - Baseline - Second-daily application cohort: 2x 10mL vials of topical RECCE®327 solution. - Day 7/ midpoint - Daily application cohort: 6x 10mL vials of topical RECCE®327 solution. - Day 7/ midpoint - Second-daily application cohort: 3x 10mL vials of topical RECCE®327 solution. Vials must then be refrigerated by the participant in their home between 2°C-8°C. A study nurse will attend the patient's home for daily or second daily application of topical RECCE®327 solution, depending on treatment cohort allocation. They will perform the following procedures: - Removal of dressings and irrigation of wound with sodium chloride 0.9% - Application of the topical RECCE®327 and re-dressing of wound - Record keeping for study and medicolegal purposes Each visit should take approximately 30 minutes and is representative of a typical home-visiting nurse follow up, however the number of visits required over the study duration are more than that of "standard care". At each visit, participants will be assessed for treatment-related adverse effects which can be escalated to the study team. The volume of RECCE®327 applied per cm2 will also be recorded. Participants will be monitored in the High Risk Foot Clinic at Liverpool Hospital face-to-face on days 7 and 14 of the trial. During these visits, topical therapy will be re-applied and standard wound care (as above) will be provided. Participants will be assessed for treatment-related adverse effects and the volume of RECCE®327 applied per cm2 will be recorded. Daily or second daily home-nursing reviews will allow the study team to quickly detect deterioration and escalate matters if required. The requirement for rescue therapy will be be assessed at each review (clinic or home-nursing). Home-visiting nurses would need to escalate this matter to the study team and an urgent clinic visit would need to be arranged. The mainstay rescue therapy would be cessation of the study drug with escalation to the appropriate systemic antimicrobial therapy. Rescue therapy may be required if there are signs of increasing infection severity, determined by the International Working Group on the Diabetic Foot (IWGDF) DFI classification as; increasing erythema, inflammation, increasing wound dimensions and/or poorer tissue quality (necrosis), involvement of deeper anatomical structures (bone, joint, tendon etc), presence of systemic signs of infection (fever, rigors etc.), increased leukocytosis and an increase in other inflammatory markers through adjunctive pathology. Rescue therapy may also be required at the end of the treatment period (14 days) where a member of the study team determines that the DFI is resolving (improvement in clinical markers and DFI score), but a clinical cure is not achieved (DFI resolution).