Diabetic Foot Ulcer (DFU)
Conditions
Keywords
Diabetic Foot Ulcer;, High Purity Type-I Collagen-Based Skin Substitute;, Acellular Intact Fish Skin Matrix;, Randomized Controlled Clinical Trial;, Multicentric Study;, Dermal Matrix
Brief summary
This is a randomized controlled clinical investigation in patients suffering from diabetic foot ulcers at multiple centres in India and Bangladesh. The study compares patient outcomes using standard wound care with a High Purity Type-I Collagen-Based Skin Substitute against standard wound care with an Acellular Intact Fish Skin Matrix.
Detailed description
The purpose of this study is to compare the safety and efficacy of a high-purity type-I collagen-based skin substitute (HPTC) versus an acellular intact fish-skin matrix (AFSM) in the treatment of diabetic foot ulcers (DFUs), each combined with standardized background wound care. Eligible participants with a Wagner Grade 1-2 target ulcer will be randomized 1:1, stratified by centre and baseline ulcer-size stratum, to receive HPTC or AFSM. The primary outcome is the proportion of participants achieving confirmed complete closure of the target ulcer by Week 12. Outcome assessment (digital planimetry and closure adjudication) is performed by assessors blinded to treatment allocation.
Interventions
Arm A - The SOC in this study is wound care covering with High Purity Type-I Collagen-Based Skin Substitute applied weekly or as needed followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous paraffin gauze, second layer - absorbent gauze pads \& third layer - soft roll and compressive wrap (crepe bandage). For participants enrolled in the optional histopathological sub-study, a 2-mm punch biopsy will be obtained from the wound edge at baseline and on Day 5 under local anesthesia. Specimens will be fixed in 10% neutral buffered formalin, paraffin-embedded, and sectioned at 4 μm for histological and immunohistochemical analysis.
DEVICEAcellular Intact Fish Skin Matrix and SOC
Arm B - The SOC in this study is wound care covering with Acellular Intact Fish Skin Matrix applied weekly or as needed followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous paraffin gauze, second layer - absorbent gauze pads \& third layer - soft roll and compressive wrap (crepe bandage). For participants enrolled in the optional histopathological sub-study, a 2-mm punch biopsy will be obtained from the wound edge at baseline and on Day 5 under local anesthesia. Specimens will be fixed in 10% neutral buffered formalin, paraffin-embedded, and sectioned at 4 μm for histological and immunohistochemical analysis.
Sponsors
Adichunchanagiri Institute of Medical Sciences, B G Nagara
Mysore Medical College and Research Institute, Mysurur
National Institute of Burn & Plastic Surgery, Dhaka
EKAGRA Health, Dhaka
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must be at least 18 years of age or older. * Subjects must have a diagnosis of type 1 or 2 diabetes mellitus. * Diabetic foot ulcer located below the malleoli, Wagner Grade 1 or 2 (University of Texas Grade 1-2), without exposed bone. * Target ulcer present for a minimum of 4 weeks, with post-debridement area of approximately 5-20 cm². * Failure to achieve ≥30% ulcer-area reduction during the run-in period, or an equivalent documented waiver (Section 12.1). * Adequate circulation to the affected foot: ankle-brachial index (ABI) between 0.7 and 1.3 (or alternative vascular criteria per protocol). * Glycated haemoglobin (HbA1c) ≤ 12%. * The subject must consent to using the prescribed off-loading method for the duration of the study. * The subject must agree to attend the scheduled study visits required by the protocol. * The subject must be willing and able to participate in the informed consent process. * Patients must have read and signed the IEC-approved ICF before screening procedures are undertaken.
Exclusion criteria
* A subject known to have a life expectancy of less than 6 months. * If the target ulcer is infected or if there is cellulitis in the surrounding skin. * Presence of osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence; Wagner Grade ≥3. * A subject that has an infection in the target ulcer that requires systemic antibiotic therapy. * A subject receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent) or cytotoxic chemotherapy. * Topical application of steroids to the ulcer surface within one month of initial screening. * A subject with a previous partial amputation on the affected foot, if the resulting deformity impedes proper offloading of the target ulcer. * A subject with glycated haemoglobin (HbA1c) greater than 12% at or within 3 months of the initial screening visit. * A subject with an acute Charcot foot, or an inactive Charcot foot that impedes proper offloading of the target ulcer. * Women who are pregnant or considering becoming pregnant within the next 6 months. * A subject with end-stage renal disease requiring dialysis; active malignancy. * A subject who participated in a clinical trial involving treatment with an investigational product within the previous 30 days. * A subject who, in the opinion of the investigator, has a medical or psychological condition that may interfere with study assessments. * A subject treated with hyperbaric oxygen therapy or a cellular and/or tissue product (CTP) in the 30 days prior to the initial screening visit. * Known hypersensitivity to HPTC or its components; known fish allergy/hypersensitivity for participants who would be allocated to AFSM.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Confirmed Complete Wound Closure | Up to Week 13 (initial closure assessed through Week 12; confirmation visit approximately 7 days later) | Complete wound closure is defined as 100% epithelialization of the target ulcer with no drainage and no clinically evident open area requiring dressing, confirmed by a blinded central adjudicator at a follow-up visit approximately 7 days after initial clinical closure is observed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Wound Area Reduction Over Time | Weeks 2, 4, 6, 8, and 12 | Percentage reduction in wound area from baseline, measured by standardized digital photography and central digital planimetry. |
| Proportion Achieving ≥50%, ≥75%, and ≥90% Wound-Area Reduction | Week 12 | Proportion of participants achieving each threshold of wound-area reduction relative to baseline. |
| Time to Confirmed Complete Wound Closure | Up to Week 13 | Time from randomization to confirmed complete closure of the target ulcer, analyzed by Kaplan-Meier methods. |
| Mean Number of Study-Product Applications | Up to Week 6 | Average number of applications of HPTC or AFSM required to achieve wound closure or study completion. |
| Number of Participants with Adverse Events | Up to Week 13 | Number of participants experiencing adverse events related to the intervention (e.g., infection, allergic reaction, local irritation). |
| Patient-Reported Quality of Life (DFS-SF) | Baseline and Week 12 | Diabetic Foot Ulcer Scale-Short Form, four subscales (physical functioning, daily activities, emotions, social functioning), 0-100 per subscale, higher = better. |
| Scar Quality (Vancouver Scar Scale) | Week 12 or at confirmed closure | Vancouver Scar Scale assessing pigmentation, pliability, height, and vascularity; total score 0-13, lower = better. |
| Ulcer Recurrence | Up to Week 13 | Recurrence of the index ulcer after confirmed closure, monitored through study completion. |
Countries
Bangladesh, India
Contacts
CONTACTNaveen Narayan
CONTACTChethan Shivannaiah
STUDY_CHAIRPrema Dhanraj, MS, MCh
Rajarajeshwari Medical College and Hospital
Outcome results
None listed