A RCT Evaluating Efficacy of Type-I Collagen Skin Substitute vs. Human Amnion Membrane in Treatment of Venous Leg Ulcers

NCT06831760 | Completed Results FDA Device

• 1 other identifier: AIMS/IEC/004/2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Venous Leg Ulcers

Keywords

venous leg ulcer; chronic leg ulcer; leg ulcer; skin substitute; high purity type-I collagen; dehydrated human amnion / chorion membrane

Outcome Measures

Primary Outcomes (7)

• 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) 1. Mild infiltration (5-10 vessels/hpf) 2. Moderate infiltration (11-20 vessels/hpf) 3. Abundant infiltration (\>20 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 1. Minimal migration (\<25% wound coverage) 2. Moderate migration (25-75% coverage) 3. Extensive migration (\>75% coverage) (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 1. Moderate cellularity, minimal matrix production 2. High cellularity, active-matrix synthesis 3. Very high activity with extensive matrix deposition (0-worse; 3-better)

  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 1. Mild chronic inflammation 2. Moderate mixed inflammation 3. Severe acute inflammation (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 1. Loose, immature collagen 2. Moderate organized collagen 3. Dense, mature collagen architecture (0-worse; 3-better)

  5 days

Secondary Outcomes (4)

• Time to Achieve Complete Wound Closure

  7 weeks

• Percentage of Subjects to Obtain Complete Closure

  7 Weeks

• Number of Patients Requiring Repeated Application

  6 Weeks

• Intervention Related Adverse Events

  6 Weeks

Other Outcomes (3)

• Change in Pain

  7 weeks including 1-week follow-up

• Improvement in Quality of Life

  7 weeks including 1-week follow-up

• Healed Wound Appearance Assessment Using Manchester Scar Scale

  7 weeks including 1-week follow-up

Study Arms (2)

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

Device: SOC and Type-I Collagen-based Skin Substitute

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

Device: SOC and Human Amnion/Chorion Membrane

Interventions

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

SOC and Type-I Collagen-based Skin Substitute

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

SOC and Human Amnion/Chorion Membrane

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be at least 18 years of age or older.
• Subjects must have a diagnosis of a venous leg ulcer (confirmed by clinical and duplex ultrasound evaluation).
• At enrolment subjects must have a target VLU with a minimum surface area of 2.0 cm2 and a maximum surface area of 25.0 cm2 measured post debridement using a ruler to measure wound area.
• The target ulcer must have been present for a minimum of 4 weeks and a maximum of 52 weeks of standard of care prior to the initial screening visit.
• The target ulcer must be located on the foot, ankle and lower leg region.
• The target ulcer must be full thickness on the foot or ankle that does not probe to bone.
• Adequate circulation to the affected foot as documented by any of the following methods performed within 3 months of the first screening visit:
• 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.

You may not qualify if:

• 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.
• A subject known to have a life expectancy of \<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.
• 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 is excluded if the resulting deformity impedes proper offloading of the target ulcer.
• A subject with autoimmune or connective tissue disorders.
• A subject with malignant wounds or non-venous ulcers.
• A subject with a serum creatinine ≥ 3.0mg/dL within 6 months of the initial screening visit.
• Women who are pregnant or considering becoming pregnant within the next 6 months and those who are breast feeding.

Sponsors & Collaborators

• Dr Naveen Narayan MS, MCh (Plastic Surgery): lead

Study Sites (1)

Adichunchanagiri Institute of Medical Sciences

Mandya, Karnataka, 571448, India

Location

Related Publications (3)

• 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.

  PMID: 29024419 BACKGROUND

• 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.

  PMID: 39649230 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.

  PMID: 25224019 BACKGROUND

MeSH Terms

Conditions

Varicose Ulcer; Leg Ulcer

Condition Hierarchy (Ancestors)

Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr Naveen N
• Organization: Adichunchanagiri Institute of Medical Sciences

naveen_uno1@yahoo.co.in

+91-9980023372

Study Officials

• Prema Dhanraj, MS, MCh

  Rajarajeshwari Medical College and Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor & HoD, Department of Plastic Reconstructive & Aesthetic Surgery

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: February 18, 2025
• Study Start: February 1, 2025
• Primary Completion: June 30, 2025
• Study Completion: July 10, 2025
• Last Updated: September 22, 2025
• Results First Posted: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)