Bioactive Smart Dressings for Diabetic Foot Ulcers: Randomized Controlled Trial

Study Overview
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Brief Summary
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We propose a randomized controlled study to assess the efficacy of: Platelet-lysate loaded sustained release thermo-gelling formulation (Platelets-SR) EPO/ISDN/UFH cryogel dressing (Trigel) As adjuncts to standard-of-care (SOC) in the treatment of chronic DFUs compared to SOC alone for patients attending the DFU outpatient clinic at the Gastroenterology Centre, Mansoura University.

Detailed Description
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The tested treatments were manufactured, tested and optimized in the research laboratories of Pharmacy School, Mansoura University under ethical approval of Pharmacy School ethics committee and Medical School IRB committee. Our primary objective is to test the hypothesis that the proposed treatments can significantly improve the wound area regression rate assessed weekly (cm2/week) for 8 weeks as compared to SOC treatment alone. Our secondary objectives are to assess the following: the time to complete wound closure, the rate of complete wound closure and the rate of partial wound closure of ≥ 50% and ≥ 75% at end-of-treatment visit (week 8). Wound closure is confirmed when the wound remains closed at two follow up visits. The occurrence of any adverse effects either locally or systemically will be surveilled in order to assess the safety profile of the test formulations.

Official Title
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Novel Bioactive Smart Dressings for Diabetic Foot Ulcers: a Randomized Controlled Trial Comparing Efficacy of PRP-loaded Lyophilized Gel vs. Erythropoietin/Isosorbide Dinitrate Cryogel Scaffold vs. Standard of Care

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Combination Product: PRP gel and SOC-treatment
* Combination Product: EPO/ISDN/UFH cryogel dressing
* Procedure: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age of ≥ 18 Type 2 Diabetes Mellitus diagnosed as per the American Diabetic Association at the time of recruitment Patients with glycated haemoglobin (HbA1C) ≤ 9% within 4 weeks prior to randomization Patients with ulcer that meets the following criteria Ulcers classified as Grade 1, stage A (1A) ulcers using University of Texas (UT) classification system (ulcers are superficial not involving tendon, capsule or tendon and are non-infected and non-ischemic) Ulcer duration of 4 weeks or longer and hard to heal despite standard of care treatment (chronic ulcers) Ulcer has undergone recent debridement (2 weeks prior to screening) Post-debridement ulcer is free of necrotic debris, foreign bodies, sinus tracts, tunnelling, and undermining and is comprised of healthy vascularized tissue Wound area at start of treatment between 2 sq.cm. and 10 sq.cm. No surgical revascularization of the limb with the DFU was done in the previous two months. Limb criteria: At least moderate blood perfusion into the affected limb as defined by Ankle Brachial Index (ABI) of 0.9 - 1.3. Patients who agree to conform to the off-loading requirements Provide written informed consent prior to admission into the study Exclusion Criteria: Type 1 Diabetes Mellitus Patients who have undergone, in the 2-week period prior to enrolment, treatment for DFU with any advanced treatment modality other than standard of care, such as growth factors, skin substitutes or other biological treatments Have a glycosylated haemoglobin (HbA1c) > 9.0% Have a body mass index (BMI) > 40 Kg/m2 Have a clinically significant cardiac, gastrointestinal, endocrine, neurological, liver, or kidney disease Anaemia (Haemoglobin < 9 g/dL) or white Blood Cells count > 11,000/μL or platelets count < 100,000/μL or > 400,000/μL or liver function tests > 3 times upper normal lab values or Creatinine > 3 mg/dL; any indication of malnourishment (Albumin < 3 g/dL); INR > 2 or any other clinically significant blood and urinalysis tests per the physician's discretion Patients with haemochromatosis or unstable hypertension Have any clinically significant chronic or acute illness during the 4 weeks prior to admission into the study, except type 2 diabetes or during screening period Patients with wounds caused by basal cell carcinoma or due to basal cell carcinoma excision Females who are pregnant, lactating, of child-bearing potential, or post-menopausal for less than 2 years, not using a medically approved method of contraception, or females who test positive on a blood-based pregnancy test. Patients with a history of allergy to one of tested components Patients on glyceryl trinitrate or Sildenafil treatment Patients with a history of any clinical or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the investigational agent or may confound the interpretation of study results or might render the patient at high risk for treatment complications Patients with active Charcot or other structural deformity that would prevent adequate off-loading of the study foot.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRP gel and SOC-treatment<br>platelet-lysate loaded lyophilized gel in addition to standard of care | Combination Product: PRP gel and SOC-treatment<br>* Platelet-lysate loaded sustained release thermo-gelling formulation<br>|
| Experimental: Trigel and SOC-treatment<br>Erythropoietin/isosorbide dinitrate loaded cryogel scaffold in addition to standard of care | Combination Product: EPO/ISDN/UFH cryogel dressing<br>* Erythropoietin/Isosorbide dinitrate loaded cryogel scaffold<br>|
| Active Comparator: standard of care alone<br>sharp debridement, saline washing and saline dressing | Procedure: Standard of Care<br>* Sharp debridement, saline washing and regular saline dressing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound area regression rate | wound area regression rate assessed weekly (cm2/week) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of complete wound closure | rate of complete wound closure (100% closure) | 8 weeks | 
| rate of partial wound closure of ≥ 75% | rate of partial wound closure of ≥ 75% | 8 weeks | 
| rate of partial wound closure of ≥ 50% | rate of partial wound closure of ≥ 50% | 8 weeks |