Larval Debridement Therapy Versus Sharp Debridement to Remove Biofilm

Study Overview
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Brief Summary
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This is a prospective study of Veterans with chronic lower extremity or diabetic foot ulcers who will be randomized to either a Larval Debridement Therapy group (Biobags every 4 days x 2 applications) or a Sharp Debridement Therapy group (standard or control weekly x 2) during an 8 day study period.

Detailed Description
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Drug resistant organisms and bacterial biofilm pose an increasing threat to the health of millions of individuals world-wide. These organisms are being identified with an alarming prevalence among persons with chronic wounds. The presence of necrotic tissue has been associated with the deterioration of open wounds and serves as a breeding ground and nutrient source for bacteria. The removal of necrotic tissue is widely accepted as required for optimal wound healing. The primary purpose of this study is to assess the efficacy of larval debridement therapy (LDT) with bagged, sterilized, live, medicinal blow fly (Lucilia sericata) larvae (or  BioBags) versus bedside sharp debridement in removing harmful bacteria, biofilm and necrotic tissue from chronic wounds to promote wound healing. Characteristics associated with chronic wound environments will be evaluated through analysis of samples of tissue taken from wound beds before and after both types of debridement. One hundred and forty patients ≥ 21 years of age (and their caregivers and wound providers)with an open, full thickness wound which is healing by secondary intention (of greater than 8 weeks duration and requires debridement) will be invited to participate. This recruitment number accounts for estimated 10% attrition rate, so final sample number is anticipated to be 296 or 128 Veteran subjects (64 in each arm) and 128 caregivers, and 6 providers (and total of 34 subjects which may be lost to follow up). Samples of wound bed tissue and slough tissue (if present) will be collected on Days 0, 4 and 8 or prior to and after each larval debridement intervention or sharp debridement (control). Photos will be taken of the wound bed on Days 0, 4 and 8 or just prior to and after each debridement method. A randomized sampling procedure will place individuals into one of two groups: The intervention group will receive larval debridement therapy once every 4 days for 2 applications (with saline moistened gauze as cover dressing changed daily) and the control group will receive sharp debridement therapy every 7 days for 2 debridements (with wound gel dressing changed daily).

Official Title
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RCT: Larval Debridement Therapy Versus Sharp Debridement to Remove Biofilm From Chronic Lower Extremity or Diabetic Foot Ulcers

Conditions
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Lower Extremity or Diabetic Foot Ulcers, Bacterial Infection

Intervention / Treatment
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* Device: Larval Debridement Therapy
* Procedure: Bedside Sharp Debridement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans over 21 years of age with chronic lower extremity or diabetic foot ulcers (wound duration over 8 weeks) who at the clinician's judgment requires wound debridement (25% or more of wound bed covered with non-viable tissue) wound size 1.5 cm (roughly the size of a quarter) or larger in diameter Exclusion Criteria: Cognitive impairment that would interfere with patient signing own Informed Consent Veterans on active anticoagulant therapy with most recent (within last week) PT/INR (international normalized ratio of prothrombin time) > 3.0, or other significant bleeding risk Active immune suppression just prior to or during study (on systemic corticosteroids* within 7 days prior, or chemotherapy for cancer or RA treatment within 4 weeks prior to study, or with diagnosis of HIV/AIDS) - *Nasal steroid sprays will not be excluded Active systemic antibiotics is an exclusion Absent dorsalis pedis pulses and Ankle Brachial Index (ABI) < 0.5 is an exclusion (indicates critical limb ischemia). Other possible reasons participants could be removed from this study include: transfers to other non-VA facilities, participant is unable to tolerate tissue sampling even with local anesthesia, and/or inability to comply with scheduled research visits. Furthermore, if the participant has significant wound healing so that sampling is not possible after the initial sampling, they will be removed from the study.

Ages Eligible for Study
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Minimum Age: 21 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Larval Debridement Therapy<br>Larval debridement therapy intervention (Biobags) filled with sterile green bottle fly maggots (larvae) placed in open, chronic lower extremity or diabetic foot ulcer once every 4 days for total of 2 applications over the 8 day study period. | Device: Larval Debridement Therapy<br>* small sterile mesh bags containing live maggots placed into an open chronic wound to remove necrotic tissue and bacterial biofilm<br>* Other names: Biobags;|
| Active Comparator: Sharp Debridement Therapy<br>Bedside sharp debridement therapy as a comparator performed by wound care clinician once every 7 days in a chronic lower extremity or diabetic foot ulcer for a total of 2 sharp debridements over the 8 day study period. | Procedure: Bedside Sharp Debridement<br>* The use of a sharp clinical instrument (currette, scalpel, scissors, forceps) by a qualified clinician to remove necrotic tissue and bacterial biofilm from an open chronic wound<br>* Other names: Sharps;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed), With Tryptic Soy Agar (TSA) Plating | Differences in total bacterial colony forming units (CFUs) between LDT and SDT arms at Day 0, with Tryptic Soy Agar (TSA) plating. Raw outcomes were natural-log transformed due to skewed distribution. Higher scores correspond to a greater number of bacterial CFUs (i.e., worse outcome). | Day 0 (Baseline), Day 4, Day 8 | 
| Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed), With MacConkey Agar Plating | Differences in total bacterial colony forming units (CFUs) between LDT and SDT arms at Day 0, with MacConkey Agar plating. Raw outcomes were natural-log transformed due to skewed distribution. Higher scores correspond to a greater number of bacterial CFUs (i.e., worse outcome). | Day 0 (Baseline), Day 4, Day 8 | 
| Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed),With Phenylethyl Alcohol (PEA) Plating | Differences in total bacterial colony forming units (CFUs) between LDT and SDT arms at Day 0, with Phenylethyl Alcohol (PEA) plating. Raw outcomes were natural-log transformed due to skewed distribution. Higher scores correspond to a greater number of bacterial CFUs (i.e., worse outcome). | Day 0 (Baseline), Day 4, Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reviewer Assessment of Visible Wound Improvement | For each patient, wound photos were taken at days 0, 4, and 8 and given to wound specialists. Wound specialists reviewed photos to assess whether there was visible reduction in amount of necrotic or non-viable tissue remaining in the wound bed at day 8--i.e., whether the wound appeared to be improved (yes vs. no). The percentage of reviewers (out of 4) who responded yes that the wound appeared improved was calculated for each patient. Thus, each patient received a score for percentage of reviewers who saw visual improvement; the means and standard deviations for these percentages were compared between LDT and SDT groups. Higher scores correspond to better outcomes (higher proportion of reviewers who responded that wounds appeared visibly improved). | Day 8 | 
| Inflammatory Biomarker MMP-9 | Using Enzyme Linked Immunosprbent Assay (ELISA), the levels of active Matrix Metalloproteinase type 9 (MMP-9) was calculated and expressed as pg/ml of wound fluid and pg/mg protein. Raw outcomes were natural-log transformed due to skewed distribution. Higher scores indicate worse outcomes. | Day 0 (Baseline), Day 4, Day 8 | 
| Inflammatory Biomarker IL6 | The levels of active IL6 was calculated using Enzyme Linked Immunosprbent Assay (ELISA) and reported in ng/ml. Raw outcomes were natural-log transformed due to skewed distribution. Higher scores indicate worse outcomes. | Day 0 (Baseline), Day 4, Day 8 | 
| Satisfaction With Debridement: Overall Satisfaction With Method, Day 8 | Satisfaction (Overall) item score. This item is from a Satisfaction with Debridement survey, designed to measure satisfaction with debridement method, aesthetic questions regarding debridement, ease of use/care, and wound pain. Individual item scores range from 0 to 10, with higher scores indicating better outcomes (higher overall satisfaction). | Day 8 | 
| Satisfaction: Aesthetic Unpleasantness of Debridement, Day 8 | Survey item score for Aesthetic Unpleasantness of debridement. This item is from a Satisfaction with Debridement survey. Individual item scores range from 0 to 10, with higher scores on the aesthetic unpleasantness item indicating worse outcomes | Day 8 | 
| Satisfaction: Difficulty of Use/Care, Day 8 | Survey item score for Difficulty of Use/Care of debridement. This item is from a Satisfaction with Debridement survey. Individual item scores range from 0 to 10, with higher scores on the difficulty item indicating worse outcome (higher difficulty of use/care for debridement method). | Day 8 | 
| Satisfaction: Wound Pain, Day 8 | Satisfaction survey to measure satisfaction with debridement method, aesthetic questions regarding debridement, ease of use/care, and wound pain. Pain was measured using the Defense and Veterans Pain Rating Scale (DVPRS). Individual item scores range from 0 to 10, with higher scores on the DVPRS indicating higher pain and worse outcomes. | Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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larva, debridement, lower extremity or diabetic foot ulcer, biofilm, infection, chronic wound