Study of Combined Topical Growth Factor and Protease Inhibitor in Chronic Wound Healing

Study Overview
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Brief Summary
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Leg and foot ulcers due to venous disease or diabetes are chronic wounds that can take 6 or more months to heal. Growth factors have been used to try and improve this healing, however, many such studies have failed, and that is thought to be due enzymes in the wound that degrade the growth factors and prevent them from working. This is a proof of concept study that will evaluate the treatment of chronic leg ulcers with topically applied growth factors that are combined with a therapy to prevent their inactivation in the wound.

Official Title
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Proof of Concept Study of Combined Topical Growth Factor and Protease Inhibitor in Chronic Wound Healing

Conditions
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Venous Ulcer, Foot Ulcer, Diabetic

Intervention / Treatment
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* Biological: Becaplermin
* Device: Promagran Dressing
* Device: Placebo Dressing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged ≥18 years Ulcer size 1-64 cm² Ulcer extends through both the epidermis and dermis, with no exposed tendon or bone Ulcer duration >3 months Ulcer located between and including the knee and ankle For venous leg ulcers - Venous refilling time <25s on photoplethysmography or abnormal venous insufficiency Duplex scan For diabetic foot ulcers - confirmed type 1 or type 2 diabetes mellitus with a haemoglobin A1C < 12% Wounds have not been treated with Promogran in the previous 4 weeks Patients able to give informed consent Exclusion Criteria: Ankle-brachial index <0.8 Ulcer with local or systemic signs of infection Patients who have been previously treated with Becaplermin gel Receiving corticosteroids or immune suppressants History of autoimmune disease Uncontrolled diabetes (baseline haemoglobin A1C > 12%) Severe rheumatoid arthritis Uncontrolled congestive heart failure Malnutrition (albumin <2.5g/dL) Unable to adhere to the protocol Known sensitivities to the wound dressings used in the trial A history of any previous malignancy pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Becaplermin/Promagran Dressing<br>Topical Becaplermin with a protease inhibitor wound dressing. | Biological: Becaplermin<br>* 0.25 cm of 100 µg/g Becaplermin gel topically per 1cm² of ulcer area applied 3 times per week for 6 weeks.<br>* Other names: Regranex;Device: Promagran Dressing<br>* 44% oxidized regenerated cellulose (ORC), 55% collagen and 1% silver-ORC wound dressing applied 3 times per week for 4 weeks.<br>|
| Active Comparator: Becaplermin/Placebo Dressing<br>Topical Becaplermin with a placebo wound dressing. | Biological: Becaplermin<br>* 0.25 cm of 100 µg/g Becaplermin gel topically per 1cm² of ulcer area applied 3 times per week for 6 weeks.<br>* Other names: Regranex;Device: Placebo Dressing<br>* Inactive wound dressing.<br>* Other names: Aquacel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Applied Growth Factors in Chronic Wound Fluid | The levels of the growth factors applied to the chronic wound will be measured using samples of the wound fluid gathered at the first two visits each week. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protease Levels in Chronic Wound Fluid | The levels of enzyme activity in the chronic wound will be measured using samples of the wound fluid gathered at the first two visits each week. | 6 weeks | 
| Chronic Wound Healing at 4 Weeks | Chronic wound healing will be measured using the VISITRAK device, which traces the outline of the chronic wound. | 4 weeks | 
| WOUNDCHEK Device Validity | The WOUNDCHEK device will be used in order to test for levels of enzyme activity in the chronic wound. This data will then be compared to the enzyme activity as determined by the levels analyzed in the chronic wound fluid. | 6 weeks | 
| Levels of Healing Biomarkers in Chronic Wound Fluid | The levels of the potential biomarker of healing GMCSF in the chronic wound fluid will be measured using samples of the chronic wound fluid collected at the first two visits each week. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous Leg Ulcer, Diabetic Foot Ulcer, Wound Healing, Growth Factor, Protease Inhibitor