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Venous leg ulcers are chronic wounds caused by venous insufficiency, leading to significant morbidity. The purpose of this randomized, controlled study is to evaluate the safety and efficacy of the application of Type-I Collagen-based Skin Substitute (HPTC) vs. Dehydrated Human Amnion/Chorion Membrane (dHCAM) in the treatment of VLUs and to compare their efficacy.
Venous leg ulcers (VLUs) are chronic wounds caused by venous insufficiency, leading to significant morbidity. Current treatment options often include compression therapy, wound debridement, and advanced dressings. Despite advances in wound care, effective treatment remains challenging. The purpose of this randomized, controlled study is to evaluate the safety and efficacy of the application of Type-I Collagen-based Skin Substitute (HPTC) vs. Dehydrated Human Amnion/Chorion Membrane (dHCAM) in the treatment of VLUs and to compare the efficacy of these two advanced wound care modalities in accelerating VLU healing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SOC and Type-I Collagen-based Skin Substitute | Other | 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 |
|
| SOC and Human Amnion/Chorion Membrane | Other | The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SOC and Type-I Collagen-based Skin Substitute | Device | 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, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Wound Area Change | Percentage wound area change from week 1 through week 7 measured manually with digital photography | 7 Weeks |
| Histopathological Parameters - Vascular Infiltration | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with Hematoxylin and Eosin (H&E) for general morphology. Vascular Infiltration: Assessed by counting new blood vessels per High Power Field (hpf) (0-3 scale) 0: Minimal vascular ingrowth (<5 vessels/hpf)
(0-worse; 3-better) | 5 days |
| Histopathological Parameters - Neo-epithelialization | Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: Hematoxylin and Eosin (H&E) for general morphology. Neo-epithelialization: Measured as epithelial migration distance from wound edge (0-3 scale) 0: No epithelial migration
(0-worse; 3-better) | 5 days |
| Histopathological Parameters - Fibroblast Activity | Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: α-SMA immunohistochemistry for fibroblast activity. Fibroblast Activity: Quantified by counting α-SMA positive fibroblasts per HPF and assessment of fibroblast morphology (0-3 scale) 0: Sparse, inactive fibroblasts
(0-worse; 3-better) |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Achieve Complete Wound Closure | The time to achieve complete wound closure of the target ulcer by the end of 7 weeks | 7 weeks |
| Percentage of Subjects to Obtain Complete Closure | The percentage of subjects that obtain complete closure over the 7 week treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Pain | Change in pain measured by a Visual Analog Scale with score range from 0 to 10, wherein 0="no pain" to 10="severe pain" | 7 weeks including 1-week follow-up |
| Improvement in Quality of Life |
Inclusion Criteria:
i. TCOM ≥30 mmHg ii. ABI between 0.7 and 1.3 iii. PVR: Biphasic iv. TBI ˃0.6 v. As an alternative arterial, Doppler ultrasound can be performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle of the target extremity.
h. If the subject has two or more ulcers, they must be separated by at least 2 cm. The largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer.
i. The subject must consent to using the prescribed off-loading method for the duration of the study.
j. The subject must agree to attend the twice-weekly/weekly study visits required by the protocol.
k. The subject must be willing and able to participate in the informed consent process.
l. Patients must have read and signed the IRB approved ICF before screening procedures are undertaken.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Prema Dhanraj, MS, MCh | Rajarajeshwari Medical College and Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Adichunchanagiri Institute of Medical Sciences | Mandya | Karnataka | 571448 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29024419 | Background | Bianchi C, Cazzell S, Vayser D, Reyzelman AM, Dosluoglu H, Tovmassian G; EpiFix VLU Study Group. A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix(R) ) allograft for the treatment of venous leg ulcers. Int Wound J. 2018 Feb;15(1):114-122. doi: 10.1111/iwj.12843. Epub 2017 Oct 11. | |
| 39649230 |
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| ID | Title | Description |
|---|---|---|
| FG000 | SOC and Type-I Collagen-based Skin Substitute | 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 SOC and Type-I Collagen-based Skin Substitute: 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, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 8, 2025 | Sep 19, 2025 |
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| SOC and Human Amnion/Chorion Membrane | Device | The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap |
|
| 5 Days |
| Histopathological Parameters - Capillary Density | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: CD31 immunohistochemistry for capillary density evaluation Capillary Density: Evaluated using CD31 staining, counted as vessels per mm² of tissue | 5 days |
| Histopathological Parameters - Inflammatory Response | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: Hematoxylin and Eosin (H&E) for general morphology Inflammatory Response: Graded semi-quantitatively (0-3 scale) 0: Minimal inflammatory infiltrate
(0-worse; 3-better) | 5 days |
| Histopathological Parameters - Collagen Deposition | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: Masson's Trichrome for collagen assessment Collagen Deposition: Assessed using Masson's Trichrome staining (0-3 scale) 0: Minimal collagen matrix
(0-worse; 3-better) | 5 days |
| 7 Weeks |
| Number of Patients Requiring Repeated Application | Number of patients requiring repeated applications of the Advanced Skin Substitute & Human Amnion/Chorion Membrane used to obtain wound closure | 6 Weeks |
| Intervention Related Adverse Events | Number of participants with intervention related adverse events related to the intervention (e.g., infection, allergic reactions) | 6 Weeks |
Change in quality of life assessed using the Wound-QoL questionnaire measured as 'not at all', 'a little', 'moderately', 'quite a lot' and 'very much' for 17 questions and total number of patients who reported improvement in Quality of Life was measured
| 7 weeks including 1-week follow-up |
| Healed Wound Appearance Assessment Using Manchester Scar Scale | The resultant new skin is assessed and documented at each visit using the Manchester Scar Scale (MSS) assessing:
Lower score denotes a better outcome using the MSS (range: 4-14). In the study, scores were categorized as such:
| 7 weeks including 1-week follow-up |
| Narayan N, Gowda S, Shivannaiah C. A Randomized Controlled Clinical Trial Comparing the Use of High Purity Type-I Collagen-Based Skin Substitute vs. Dehydrated Human Amnion/Chorion Membrane in the Treatment of Diabetic Foot Ulcers. Cureus. 2024 Dec 5;16(12):e75182. doi: 10.7759/cureus.75182. eCollection 2024 Dec. |
| 25224019 | Background | Serena TE, Carter MJ, Le LT, Sabo MJ, DiMarco DT; EpiFix VLU Study Group. A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair Regen. 2014 Nov-Dec;22(6):688-93. doi: 10.1111/wrr.12227. Epub 2015 Jan 8. |
| FG001 | SOC and Human Amnion/Chorion Membrane | The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing SOC and Human Amnion/Chorion Membrane: The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | SOC and Type-I Collagen-based Skin Substitute | 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 SOC and Type-I Collagen-based Skin Substitute: 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, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap |
| BG001 | SOC and Human Amnion/Chorion Membrane | The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing SOC and Human Amnion/Chorion Membrane: The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Ulcer duration | Mean | Standard Deviation | Months |
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| Ulcer size | Mean | Standard Deviation | square centimeters |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Wound Area Change | Percentage wound area change from week 1 through week 7 measured manually with digital photography | Posted | Mean | Standard Deviation | percentage wound area reduction | 7 Weeks |
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| Primary | Histopathological Parameters - Vascular Infiltration | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with Hematoxylin and Eosin (H&E) for general morphology. Vascular Infiltration: Assessed by counting new blood vessels per High Power Field (hpf) (0-3 scale) 0: Minimal vascular ingrowth (<5 vessels/hpf)
(0-worse; 3-better) | Posted | Mean | Standard Deviation | score on a scale (0-worse; 3-better) | 5 days |
| |||||||||||||||||||||||||||||||
| Primary | Histopathological Parameters - Neo-epithelialization | Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: Hematoxylin and Eosin (H&E) for general morphology. Neo-epithelialization: Measured as epithelial migration distance from wound edge (0-3 scale) 0: No epithelial migration
(0-worse; 3-better) | Posted | Mean | Standard Deviation | score on a scale (0-worse; 3-better) | 5 days |
| |||||||||||||||||||||||||||||||
| Primary | Histopathological Parameters - Fibroblast Activity | Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: α-SMA immunohistochemistry for fibroblast activity. Fibroblast Activity: Quantified by counting α-SMA positive fibroblasts per HPF and assessment of fibroblast morphology (0-3 scale) 0: Sparse, inactive fibroblasts
(0-worse; 3-better) | Posted | Mean | Standard Deviation | score on a scale (0-worse; 3-better) | 5 Days |
| |||||||||||||||||||||||||||||||
| Primary | Histopathological Parameters - Capillary Density | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: CD31 immunohistochemistry for capillary density evaluation Capillary Density: Evaluated using CD31 staining, counted as vessels per mm² of tissue | Posted | Mean | Standard Deviation | number of vessels per mm² of tissue | 5 days |
| |||||||||||||||||||||||||||||||
| Primary | Histopathological Parameters - Inflammatory Response | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: Hematoxylin and Eosin (H&E) for general morphology Inflammatory Response: Graded semi-quantitatively (0-3 scale) 0: Minimal inflammatory infiltrate
(0-worse; 3-better) | Posted | Mean | Standard Deviation | score on a scale (0-worse; 3-better) | 5 days |
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| Primary | Histopathological Parameters - Collagen Deposition | Histopathological Assessment - Before application and on the 5th day post-application of either HPTC or dHCAM, a 2mm punch biopsy was obtained from the wound edge extending into the wound bed under local anaesthesia. Serial sections of 4μm thickness were prepared and stained with: Masson's Trichrome for collagen assessment Collagen Deposition: Assessed using Masson's Trichrome staining (0-3 scale) 0: Minimal collagen matrix
(0-worse; 3-better) | Posted | Mean | Standard Deviation | score on a scale (0-worse; 3-better) | 5 days |
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| Secondary | Time to Achieve Complete Wound Closure | The time to achieve complete wound closure of the target ulcer by the end of 7 weeks | Posted | Mean | Standard Deviation | days | 7 weeks |
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| Secondary | Percentage of Subjects to Obtain Complete Closure | The percentage of subjects that obtain complete closure over the 7 week treatment period | Posted | Count of Participants | Participants | 7 Weeks |
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| Secondary | Number of Patients Requiring Repeated Application | Number of patients requiring repeated applications of the Advanced Skin Substitute & Human Amnion/Chorion Membrane used to obtain wound closure | Posted | Count of Participants | Participants | 6 Weeks |
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| Secondary | Intervention Related Adverse Events | Number of participants with intervention related adverse events related to the intervention (e.g., infection, allergic reactions) | Posted | Count of Participants | Participants | 6 Weeks |
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| Other Pre-specified | Change in Pain | Change in pain measured by a Visual Analog Scale with score range from 0 to 10, wherein 0="no pain" to 10="severe pain" | Posted | Mean | Standard Deviation | score on a scale | 7 weeks including 1-week follow-up |
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| Other Pre-specified | Improvement in Quality of Life | Change in quality of life assessed using the Wound-QoL questionnaire measured as 'not at all', 'a little', 'moderately', 'quite a lot' and 'very much' for 17 questions and total number of patients who reported improvement in Quality of Life was measured | Posted | Count of Participants | Participants | 7 weeks including 1-week follow-up |
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| Other Pre-specified | Healed Wound Appearance Assessment Using Manchester Scar Scale | The resultant new skin is assessed and documented at each visit using the Manchester Scar Scale (MSS) assessing:
Lower score denotes a better outcome using the MSS (range: 4-14). In the study, scores were categorized as such:
| Posted | Count of Participants | Participants | 7 weeks including 1-week follow-up |
|
7 Weeks including 1 week follow up
All the study participants were considered at risk for adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SOC and Type-I Collagen-based Skin Substitute | 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 SOC and Type-I Collagen-based Skin Substitute: 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, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap | 0 | 30 | 0 | 30 | 2 | 30 |
| EG001 | SOC and Human Amnion/Chorion Membrane | The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing SOC and Human Amnion/Chorion Membrane: The SOC in this study is wound care covering with Dehydrated Human Amnion/Chorion Membrane followed by a padded 3-layer dressing comprised of first layer - non-adherent and porous, second layer - absorbent 4x4 gauze pads & third layer - soft roll and compressive wrap | 0 | 30 | 0 | 30 | 3 | 30 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infections | Infections and infestations | Non-systematic Assessment |
| ||
| Mild local reaction | Immune system disorders | Non-systematic Assessment |
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Single-centre design may limit generalizability to other healthcare settings and populations.
Relatively short follow-up period (7 weeks), while sufficient for assessing acute healing outcomes, may not capture long-term outcomes, recurrence rates or durability of treatment effects. T Study was not completely blinded due to the nature of the interventions Study included a specific range of wound sizes and may not be generalizable to very large wounds.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Naveen N | Adichunchanagiri Institute of Medical Sciences | +91-9980023372 | naveen_uno1@yahoo.co.in |
| Prot_006.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 8, 2025 | Sep 19, 2025 | SAP_007.pdf |
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| ID | Term |
|---|---|
| D014647 | Varicose Ulcer |
| D007871 | Leg Ulcer |
| ID | Term |
|---|---|
| D014648 | Varicose Veins |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D012883 | Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| Between 18 and 65 years |
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| >=65 years |
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