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Completed

NCT Number: NCT06831760

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

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.

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Key information

Conditions

Venous Leg Ulcers Cardiovascular Diseases Leg Ulcer Skin Diseases Skin Ulcer Skin and Connective Tissue Diseases Varicose Ulcer Varicose Veins Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Adichunchanagiri Institute of Medical Sciences

Mandya, Karnataka, 571448, India

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

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

  • 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.
  • A subject with end stage renal disease requiring dialysis.
  • 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.
  • History of autoimmune disease, malignancy, or uncontrolled diabetes (HbA1c >10%).
  • Allergy to components of High Purity Type-I Collagen-based Skin Substitute or Dehydrated Human Amnion/Chorion Membrane.

Treatment and study plan

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 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

Primary outcomes

  1. Percentage Wound Area Change

    Time frame: 7 Weeks

    Percentage wound area change from week 1 through week 7 measured manually with digital photography

  2. Histopathological Parameters - Vascular Infiltration

    Time frame: 5 days

    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)

    • Mild infiltration (5-10 vessels/hpf)
    • Moderate infiltration (11-20 vessels/hpf)
    • Abundant infiltration (>20 vessels/hpf)

    (0-worse; 3-better)

  3. Histopathological Parameters - Neo-epithelialization

    Time frame: 5 days

    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

    • Minimal migration (<25% wound coverage)
    • Moderate migration (25-75% coverage)
    • Extensive migration (>75% coverage)

    (0-worse; 3-better)

  4. Histopathological Parameters - Fibroblast Activity

    Time frame: 5 Days

    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

    • Moderate cellularity, minimal matrix production
    • High cellularity, active-matrix synthesis
    • Very high activity with extensive matrix deposition

    (0-worse; 3-better)

  5. Histopathological Parameters - Capillary Density

    Time frame: 5 days

    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

  6. Histopathological Parameters - Inflammatory Response

    Time frame: 5 days

    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

    • Mild chronic inflammation
    • Moderate mixed inflammation
    • Severe acute inflammation

    (0-worse; 3-better)

  7. Histopathological Parameters - Collagen Deposition

    Time frame: 5 days

    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

    • Loose, immature collagen
    • Moderate organized collagen
    • Dense, mature collagen architecture

    (0-worse; 3-better)

Secondary outcomes

  1. Time to Achieve Complete Wound Closure

    Time frame: 7 weeks

    The time to achieve complete wound closure of the target ulcer by the end of 7 weeks

  2. Percentage of Subjects to Obtain Complete Closure

    Time frame: 7 Weeks

    The percentage of subjects that obtain complete closure over the 7 week treatment period

  3. Number of Patients Requiring Repeated Application

    Time frame: 6 Weeks

    Number of patients requiring repeated applications of the Advanced Skin Substitute & Human Amnion/Chorion Membrane used to obtain wound closure

  4. Intervention Related Adverse Events

    Time frame: 6 Weeks

    Number of participants with intervention related adverse events related to the intervention (e.g., infection, allergic reactions)

Other outcomes

  1. Change in Pain

    Time frame: 7 weeks including 1-week follow-up

    Change in pain measured by a Visual Analog Scale with score range from 0 to 10, wherein 0="no pain" to 10="severe pain"

  2. Improvement in Quality of Life

    Time frame: 7 weeks including 1-week follow-up

    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

  3. Healed Wound Appearance Assessment Using Manchester Scar Scale

    Time frame: 7 weeks including 1-week follow-up

    The resultant new skin is assessed and documented at each visit using the Manchester Scar Scale (MSS) assessing:

    • Colour: Perfect - 1, Slight mismatch - 2, Obvious mismatch - 3, Gross mismatch - 4
    • Finish: Matte - 1, Shiny - 2
    • Contour: Flush with surrounding skin - 1, Slightly proud / indented - 2, Hypertrophic - 3, Keloid - 4
    • Distortion: None -1, Mild - 2, Moderate - 3, Severe - 4

    Lower score denotes a better outcome using the MSS (range: 4-14). In the study, scores were categorized as such:

    • Excellent: Scores 4 and 5
    • Good: Scores from 6 to 8
    • Fair: Scores from 9 to 11
    • Poor: Scores from 12 to 14

Sponsors and collaborators

Lead sponsor

Dr Naveen Narayan MS, MCh (Plastic Surgery)

Other

Registry information

Official study title

A Randomized, Controlled Clinical Trial Evaluating the Efficacy of Type-I Collagen-based Skin Substitute vs. Dehydrated Human Amnion/Chorion Membrane in the Treatment of Venous Leg Ulcers

Important dates

Study start
2025
Primary completion
2025
Study completion
2025
First posted
Feb 18, 2025
Registry last updated
Sep 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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