Lower Extremity or Diabetic Foot UlcersNCT02294175
Larval Debridement Therapy Versus Sharp Debridement to Remove Biofilm
A study testing Larval Debridement Therapy and Bedside Sharp Debridement in people with Lower Extremity or Diabetic Foot Ulcers and Bacterial Infection, run by North Florida Foundation for Research and Education at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Lower Extremity or Diabetic Foot Ulcers, Bacterial Infection
- What is being tested?
- Larval Debridement Therapy and Bedside Sharp Debridement
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2015to 24 Mar 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
North Florida Regional Medical Center
Gainesville, Florida, 32605
North Florida / South Georgia Veterans Health System
Gainesville, Florida, 32608
About this study
Official title: RCT: Larval Debridement Therapy Versus Sharp Debridement to Remove Biofilm From Chronic Lower Extremity or Diabetic Foot Ulcers
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.
Read the detailed description
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).
- Being tested
- Larval Debridement Therapy, Bedside Sharp Debridement
- Keywords
- larva, debridement, lower extremity or diabetic foot ulcer, biofilm, infection, chronic wound
- Medical subject headings
- Diabetic Foot, Bacterial Infections, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Larval Debridement TherapyDevice
Also called LDT, Maggot Debridement, MDT, Maggots
small sterile mesh bags containing live maggots placed into an open chronic wound to remove necrotic tissue and bacterial biofilm
Bedside Sharp DebridementProcedure or surgery
Also called Sharp debridement, Sharps
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
| Study group | Role | What they receive |
|---|---|---|
| Larval Debridement Therapy | Active comparator | 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. Receives: Device: Larval Debridement Therapy |
| Sharp Debridement Therapy | Active comparator | 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. Receives: Procedure: Bedside Sharp Debridement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: Day 0 (Baseline), Day 4, Day 8
Secondary outcomes (7)
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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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).
Measured: 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.
Measured: Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2017
- Study completion24 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lower Extremity or Diabetic Foot UlcersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- North Florida Foundation for Research and Education
- Sponsor type
- University, hospital or other
- Collaborators
- North Florida/South Georgia Veterans Health System, Biomonde
- Responsible party
- Sponsor
- Investigators
- Linda J Cowan, PhD, Principal investigator, North Florida/South Georgia Veterans Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02294175
- Sponsor's protocol ID
- 201400590
- Status last verified
- Mar 2020
- First submitted
- 17 Nov 2014
- Last updated
- 7 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sen CK, Roy S, Mathew-Steiner SS, Gordillo GM. Biofilm Management in Wound Care. Plast Reconstr Surg. 2021 Aug 1;148(2):275e-288e. doi: 10.1097/PRS.0000000000008142.
PubMed 34398099
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RCT: Larval Debridement Therapy Versus Sharp Debridement to Remove Biofilm From Chronic Lower Extremity or Diabetic Foot Ulcers
- ClinicalTrials.gov ID
- NCT02294175
- Acronym / sponsor ID
- 201400590
- Keywords
- larva, debridement, lower extremity or diabetic foot ulcer, biofilm, infection, chronic wound
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- North Florida Foundation for Research and EducationUniversity, hospital or other
- Collaborators
- North Florida/South Georgia Veterans Health System, Biomonde
- Study start
- Jan 2015
- Primary completion
- Dec 2017 (actual)
- Study completion
- 24 Mar 2018 (actual)
- First posted
- 19 Nov 2014 (estimated)
- Results
- Posted 7 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Larval Debridement Therapy | Active comparator | Device: Larval Debridement TherapyLarval 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. |
| Sharp Debridement Therapy | Active comparator | Procedure: Bedside Sharp DebridementBedside 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Larval Debridement TherapyAlso: LDT, Maggot Debridement, MDT, Maggotssmall sterile mesh bags containing live maggots placed into an open chronic wound to remove necrotic tissue and bacterial biofilm | Device | Larval Debridement Therapy |
| Bedside Sharp DebridementAlso: Sharp debridement, SharpsThe 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 | Procedure or surgery | Sharp Debridement Therapy |
Primary outcome
Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed), With Tryptic Soy Agar (TSA) Plating
Time frame: Day 0 (Baseline), Day 4, Day 8
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).
Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed), With MacConkey Agar Plating
Time frame: Day 0 (Baseline), Day 4, Day 8
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).
Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed),With Phenylethyl Alcohol (PEA) Plating
Time frame: Day 0 (Baseline), Day 4, Day 8
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).
7 secondary outcomes
Reviewer Assessment of Visible Wound Improvement
Time frame: Day 8
Inflammatory Biomarker MMP-9
Time frame: Day 0 (Baseline), Day 4, Day 8
Inflammatory Biomarker IL6
Time frame: Day 0 (Baseline), Day 4, Day 8
Satisfaction With Debridement: Overall Satisfaction With Method, Day 8
Time frame: Day 8
Satisfaction: Aesthetic Unpleasantness of Debridement, Day 8
Time frame: Day 8
Satisfaction: Difficulty of Use/Care, Day 8
Time frame: Day 8
Satisfaction: Wound Pain, Day 8
Time frame: Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34398099Sen CK, Roy S, Mathew-Steiner SS, Gordillo GM. Biofilm Management in Wound Care. Plast Reconstr Surg. 2021 Aug 1;148(2):275e-288e. doi: 10.1097/PRS.0000000000008142.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda J Cowan, PhD principal investigator
North Florida/South Georgia Veterans Health System
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Larval Debridement Therapy and Bedside Sharp Debridement in people with Lower Extremity or Diabetic Foot Ulcers and Bacterial Infection, run by North Florida Foundation for Research and Education at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Bacteria Colony Forming Units (CFUs; Natural-log Transformed), With Tryptic Soy Agar (TSA) Plating (time frame: Day 0 (Baseline), Day 4, Day 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02294175, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2020.