Investigation of a Novel Wound Gel to Improve Wound Healing in Chronic Wounds

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blinded, single site study examining the impact of a biofilm-based treatment of chronic wounds of the lower extremity. 200 subjects will be enrolled in this study. Benzalkonium solution wound irrigation and Benzalkonium wound gel will be compared to standard of care wound preparation and dressing (NS wound irrigation and hydrocolloid gel) following local debridement. Wounds will be assessed maximum of 12 weeks with a minimum of 4 follow up visits. Patients will be recruited from the general wound clinic population. No enticement will be offered and participation will be completely voluntary. At enrollment and at each follow up visit the wound will be assessed for size (length, width, and depth), signs of infection or irritation, qualitative and quantitative cultures will be taken before and after debridement, patients will be assessed for compliance to the treatment protocol, satisfaction with their treatment, any adverse effects of the treatment, and hospitalizations since last assessment. It is anticipated that enrollment and completion of the study will take 1 year.

Detailed Description
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The role of biofilm in causing wound infections and preventing healing is unclear. Preliminary data suggests that persistent biofilm following excisional debridement may re-inoculate clean wounds leading to infection. Additionally, this data also suggests that persistent biofilm leads to chronic wound inflammation. Novel wound gels have been developed which claim to disrupt biofilm and kill biofilm producing bacteria. Patients presenting with a chronic wound will be randomized to receive treatment with a novel anti-biofilm solution BlastX™(benzalkonium gel) or standard of care. All patients presenting with a chronic wound (>4 weeks duration) will be assessed for eligibility in the study. If eligible, subjects will be randomized into Cohort A (debridement, NS irrigation, SOC topical wound treatment), Cohort B (debridement, benzalkonium irrigation, SOC topical wound treatment), Cohort C (debridement, NS irrigation, and benzalkonium topical wound treatment) of Cohort D (debridement, benzalkonium irrigation, and benzalkonium topical wound treatment). Subjects will receive this treatment until the wound is completely healed or they are exited from the study. Infection of chronic wounds is a multifactorial process involving the interplay between host factors, the condition of the wound, and the number and virulence of bacterial species that flourish and critically colonize in the tissue. 1 It is widely recognized that the microorganisms colonizing in these wounds are biofilm producers. 2, 3, 4, 5 Biofilm is a polymeric slime layer made up of polymeric sugars, microbial and/or host DNA, microbial proteins and host molecules that encapsulate microorganisms.5 This limits the reach of the host immune system and antibacterial agents. Biofilm formation has been associated with the emergence of a diverse group of opportunistic pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa, which contribute to recurrent infections by modifying environmental parameters.4 Excisional debridement is the standard of care for chronic wound management and has shown to be effective against biofilm. However, studies have shown that biofilm formation recurs within 24hrs of debridement. Common topical wound preparations contain silver, iodine, honey, or chlorhexidine; none of which have shown efficacy against biofilm.1 Recent studies have reported that when targeting and disrupting the wound biofilm matrix, wound healing outcomes are improved and there is a significant decrease in biofilm-related infections. 3, 5 To date, there is no widely accepted topical agent which targets biofilm. Preliminary and invitro studies have shown benzalkonium chloride to be an effective agent to disrupt biofilm and prevent recolonization. An example of a commercially available formulation of benzalkonium chloride is Benzalkonium gel wound gel and Benzalkonium solution wound irrigation. There is insufficient clinical data suggesting whether a biofilm focused approach is superior or inferior to standard of care treatment. In order to determine the clinical efficacy of a biofilm-focused approached against current stand of care treatment, this study outlines a clinical study evaluating the outcomes of patients treated with Benzalkonium gel and Benzalkonium solution compared to standard of care wound gel and irrigation.

Official Title
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Investigating the Effect of an Anti-Biofilm Solution to Reduce Bacterial Burden and Accelerate Healing in Chronic Wounds.

Conditions
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Wound Infection

Intervention / Treatment
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* Drug: Benzalkonium Gel
* Other: standard of care topical gel
* Procedure: Debridement
* Drug: benzalkonium irrigation
* Other: Saline Irrigation (SOC Irrigation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18-99 Chronic wound requiring debridement Wound located anywhere on the body Able to comply with clinical trial requirements Exclusion Criteria: Patient unable or unwilling to comply with study requirements Disease or treatment causing substantial immunosuppression History of allergic reaction to benzalkonium Transplant recipient

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SOC GROUP [Cohort A]<br>Debridement, SOC irrigation & SOC topical gel | Other: standard of care topical gel<br>* standard of care topical gel (hydrocolloid topical gel)<br>* Other names: Topical Antibacterial gel;Procedure: Debridement<br>* Removing dead tissue from infected wound (in clinic)<br>* Other names: local debridement;Other: Saline Irrigation (SOC Irrigation)<br>* Normal Saline Irrigation (SOC Irrigation)<br>* Other names: SOC Irrigation;|
| Active Comparator: SOC TOPICAL GEL & TORRENT X GROUP [Cohort B]<br>Debridement, benzalkonium irrigation & SOC topical gel | Other: standard of care topical gel<br>* standard of care topical gel (hydrocolloid topical gel)<br>* Other names: Topical Antibacterial gel;Procedure: Debridement<br>* Removing dead tissue from infected wound (in clinic)<br>* Other names: local debridement;Drug: benzalkonium irrigation<br>* washing and lavaging in clinic with benzalkonium irrigation<br>* Other names: TorrentX;|
| Active Comparator: BLASTX and SALINE (SOC) GROUP [Cohort C]<br>Debridement, SOC saline irrigation & benzalkonium gel | Drug: Benzalkonium Gel<br>* antibiofilm solution (BlastX) topical wound gel<br>* Other names: BlastX;Procedure: Debridement<br>* Removing dead tissue from infected wound (in clinic)<br>* Other names: local debridement;Other: Saline Irrigation (SOC Irrigation)<br>* Normal Saline Irrigation (SOC Irrigation)<br>* Other names: SOC Irrigation;|
| Active Comparator: BLASTX and TORRENTX GROUP [Cohort D]<br>Debridement, benzalkonium irrigation & benzalkonium gel | Drug: Benzalkonium Gel<br>* antibiofilm solution (BlastX) topical wound gel<br>* Other names: BlastX;Procedure: Debridement<br>* Removing dead tissue from infected wound (in clinic)<br>* Other names: local debridement;Drug: benzalkonium irrigation<br>* washing and lavaging in clinic with benzalkonium irrigation<br>* Other names: TorrentX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colony Forming Units Count Measure (Primary Measure) | The primary outcome is the change in CFU counts after treatment with Benzalkonium solution/Benzalkonium gel or SOC. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in index ulcer size measured in cm squared (Secondary endpoints) | Change in index ulcer size measured in cm squared | 12 weeks | 
| Duration of index ulcer measured in weeks (Secondary endpoints) | Duration of index ulcer measured in weeks | 12 weeks |