Treatment of Pressure Ulcers Using Biological Skin Substitutes

Treatment of Pressure Ulcers Using Biological Skin Substitutes: A Comparison of High Purity Type-I Collagen and Amnion/Chorion Membranes

Pressure ulcers, also known as decubitus ulcers or bedsores, are localized injuries to the skin and underlying tissue resulting from prolonged pressure. Management of pressure sores is crucial due to their association with increased morbidity, healthcare costs, and reduced quality of life. This study aims to evaluate the efficacy of two treatment modalities: Type-I Collagen-based Skin Substitute (HPTC) vs. Dehydrated Human Amnion/Chorion Membrane (dHCAM)

Study Overview

• Status: Completed
• Conditions: Pressure Sore
• Intervention / Treatment: Device: Type-I Collagen-based Skin Substitute and SOC; Device: Human Amnion/Chorion Membrane and SOC

Detailed Description

Pressure ulcers, also known as decubitus ulcers or bedsores, are localized injuries to the skin and underlying tissue resulting from prolonged pressure. They are prevalent in individuals with limited mobility, such as the elderly and those with spinal cord injuries, particularly in long-term care settings. Effective management of pressure ulcers is crucial to prevent complications and improve patient outcomes, includes pressure relief, wound care, and advanced therapies such as bioengineered skin substitutes. Management of pressure sores is crucial due to their association with increased morbidity, healthcare costs, and reduced quality of life. This study aims to evaluate the efficacy of two treatment modalities: Type-I Collagen-based Skin Substitute (HPTC) vs. Dehydrated Human Amnion/Chorion Membrane (dHCAM) in promoting the healing of pressure ulcers. While both products are used in wound management, direct comparative studies evaluating their efficacy in treating pressure ulcers are limited.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Karnataka
    • Mandya, Karnataka, India, 571448
      • Adichunchanagiri Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must be at least 18 years of age or older
2. Presence of a Stage II or Stage III pressure ulcer, as defined by the National Pressure Ulcer Advisory Panel
3. Ulcer size between 5 cm² and 25 cm²
4. Ulcer duration of at least 4 weeks prior to enrollment
5. The subject must agree to attend the twice-weekly/weekly study visits required by the protocol
6. The subject must be willing and able to participate in the informed consent process
7. Adequate blood supply to the affected area, confirmed by clinical assessment

Exclusion Criteria:

1. A subject known to have a life expectancy of <6 months
2. Presence of infection in the ulcer requiring systemic antibiotics.
3. Known allergy to components of HPTC or dHCAM.
4. Participation in another wound care study within the last 30 days.
5. A subject with autoimmune or connective tissue disorders.
6. Women who are pregnant or considering becoming pregnant within the next 6 months and those who are breast feeding.
7. History of autoimmune disease, immunosuppressive therapy, malignancy, or uncontrolled diabetes (HbA1c >10%)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High Purity 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	Device: Type-I Collagen-based Skin Substitute and SOC; 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
Active Comparator: Dehydrated 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	Device: Human Amnion/Chorion Membrane and SOC; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Wound Area	Percent Change in Wound Area from week 1 through week 7 measured manually with digital photography	7 weeks
Histopathological Parameters - Vascular Infiltration	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)	Baseline (Day 0), Day 5
Histopathological Parameters - Neo-epithelialization	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)	Baseline (Day 0), Day 5
Histopathological Parameters - Fibroblast Activity	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)	Baseline (Day 0), Day 5
Histopathological Parameters - Inflammatory Response	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-better; 3-worse)	Baseline (Day 0), Day 5
Histopathological Parameters - Capillary Density	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 More the vessels per square centimeters better	Baseline (Day 0), Day 5
Histopathological Parameters - Collagen Deposition	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)	Baseline (Day 0), Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Wound Closure Rates	Percentage of subjects to obtain complete closure, defined as 100% epithelialization with no drainage, of the target ulcer was determined by the proportion of subjects that obtain complete closure over the 6-week treatment period and additional 1 week follow up	7 weeks
Wound Size Progression Over Time	Mean wound sizes at each time point for both treatment groups assessing change in wound size throughout the study period. Assessed from baseline, through day 5, 14th day, 21 st day, 28th, 35th and 42nd days of HPTC or dHACM application	6 weeks
Mean Number of Repeated Application	Mean number of reapplications of the HPTC & dHACM used to obtain wound closure over 6 Weeks	6 weeks
Adverse Events	Adverse events (e.g., infection, allergic reactions)	6 weeks
Patient Treatment Satisfaction	Patient treatment satisfaction will be assessed by using a validated 5-point Likert scale questionnaire administered at 7 weeks post-treatment initiation. The questionnaire evaluated overall treatment satisfaction, comfort during application, perceived effectiveness, and willingness to recommend the treatment to others, measured with score range from 1 to 5, wherein 1="Extremally Unsatisfied" to 5="Extremally Satisfied"	7 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change 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	7 weeks

Collaborators and Investigators

• Sponsor: Adichunchanagiri Institute of Medical Sciences, B G Nagara
• Investigators: Study Chair: Prema Dhanraj, MS, MCh, Rajarajeshwari Medical College and Hospital

Publications and helpful links

General Publications

• 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.
• Bergstrom N, Horn SD, Rapp MP, Stern A, Barrett R, Watkiss M. Turning for Ulcer ReductioN: a multisite randomized clinical trial in nursing homes. J Am Geriatr Soc. 2013 Oct;61(10):1705-13. doi: 10.1111/jgs.12440. Epub 2013 Sep 19.
• Vecin NM, Kirsner RS. Skin substitutes as treatment for chronic wounds: current and future directions. Front Med (Lausanne). 2023 Aug 29;10:1154567. doi: 10.3389/fmed.2023.1154567. eCollection 2023.
• Berhane CC, Brantley K, Williams S, Sutton E, Kappy C. An evaluation of dehydrated human amnion/chorion membrane allografts for pressure ulcer treatment: a case series. J Wound Care. 2019 May 1;28(Sup5):S4-S10. doi: 10.12968/jowc.2019.28.Sup5.S4.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Actual): July 10, 2025
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): February 28, 2025

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Pressure Sore; High Purity Type I Collagen; Helicoll; Biological Skin Substitute; Dehydrated Human Amnion/Chorion Membrane
• Additional Relevant MeSH Terms: Skin Diseases; Skin Ulcer; Skin and Connective Tissue Diseases; Pressure Ulcer
• Other Study ID Numbers: AIMS/IEC/012/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes