Pressure Sore
Conditions
Keywords
Pressure Sore, High Purity Type I Collagen, Helicoll, Biological Skin Substitute, Dehydrated Human Amnion/Chorion Membrane
Brief summary
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)
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.
Interventions
DEVICEType-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
DEVICEHuman 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
Sponsors
Adichunchanagiri Institute of Medical Sciences, B G Nagara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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%)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Histopathological Parameters - Collagen Deposition | Baseline (Day 0), Day 5 | 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) |
| Percent Change in Wound Area | 7 weeks | Percent Change in Wound Area from week 1 through week 7 measured manually with digital photography |
| Histopathological Parameters - Vascular Infiltration | Baseline (Day 0), Day 5 | 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) |
| Histopathological Parameters - Neo-epithelialization | Baseline (Day 0), Day 5 | 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) |
| Histopathological Parameters - Fibroblast Activity | Baseline (Day 0), Day 5 | 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) |
| Histopathological Parameters - Inflammatory Response | Baseline (Day 0), Day 5 | 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-better; 3-worse) |
| Histopathological Parameters - Capillary Density | Baseline (Day 0), Day 5 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Wound Closure Rates | 7 weeks | 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 |
| Wound Size Progression Over Time | 6 weeks | 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 |
| Mean Number of Repeated Application | 6 weeks | Mean number of reapplications of the HPTC & dHACM used to obtain wound closure over 6 Weeks |
| Adverse Events | 6 weeks | Adverse events (e.g., infection, allergic reactions) |
| Patient Treatment Satisfaction | 7 weeks | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life | 7 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 |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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 | 40 |
| 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
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 | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | High Purity Type-I Collagen-based Skin Substitute | Total | Dehydrated Human Amnion/Chorion Membrane |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 39 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 41 Participants | 19 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment India | 40 Participants | 80 Participants | 40 Participants |
| Sex: Female, Male Female | 12 Participants | 30 Participants | 18 Participants |
| Sex: Female, Male Male | 28 Participants | 50 Participants | 22 Participants |
| Ulcer duration | 2.1 Months STANDARD_DEVIATION 1.1 | 2.2 Months STANDARD_DEVIATION 1.15 | 2.3 Months STANDARD_DEVIATION 1.2 |
| Ulcer Location Distribution Elbow | 2 Participants | 4 Participants | 2 Participants |
| Ulcer Location Distribution Gluteal region | 16 Participants | 32 Participants | 16 Participants |
| Ulcer Location Distribution Heel | 6 Participants | 10 Participants | 4 Participants |
| Ulcer Location Distribution Lateral malleolus | 5 Participants | 11 Participants | 6 Participants |
| Ulcer Location Distribution Sacral region | 11 Participants | 23 Participants | 12 Participants |
| Ulcer size | 14.9 square centimeters STANDARD_DEVIATION 2.1 | 14.95 square centimeters STANDARD_DEVIATION 1.94 | 15.0 square centimeters STANDARD_DEVIATION 1.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 2 / 40 | 6 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
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
Time frame: Baseline (Day 0), Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Capillary Density | 47.3 vessels per square centimeters | Standard Deviation 8.2 |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Capillary Density | 28.7 vessels per square centimeters | Standard Deviation 9.6 |
Primary
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 1. Loose, immature collagen 2. Moderate organized collagen 3. Dense, mature collagen architecture (0-worse; 3-better)
Time frame: Baseline (Day 0), Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Collagen Deposition | 2.63 score on a scale | Standard Deviation 0.49 |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Collagen Deposition | 1.77 score on a scale | Standard Deviation 0.63 |
Primary
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 1. Moderate cellularity, minimal matrix production 2. High cellularity, active-matrix synthesis 3. Very high activity with extensive matrix deposition (0-worse; 3-better)
Time frame: Baseline (Day 0), Day 5
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 0 | 7 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 1 | 17 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 2 | 13 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 3 | 3 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 0 | 0 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 1 | 2 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 2 | 5 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 3 | 33 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 3 | 7 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 0 | 12 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 0 | 3 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 1 | 16 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 2 | 15 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 2 | 10 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 5 Post Application | Grade 1 | 15 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Fibroblast Activity | Day 0 / Baseline | Grade 3 | 2 Participants |
Primary
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 1. Mild chronic inflammation 2. Moderate mixed inflammation 3. Severe acute inflammation (0-better; 3-worse)
Time frame: Baseline (Day 0), Day 5
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 0 | 21 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 1 | 14 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 2 | 5 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 3 | 0 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 0 | 20 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 1 | 17 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 2 | 3 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 3 | 0 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 3 | 4 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 0 | 12 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 0 | 9 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 1 | 16 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 2 | 15 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 2 | 11 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 5 Post Application | Grade 1 | 12 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Inflammatory Response | Day 0 / Baseline | Grade 3 | 1 Participants |
Primary
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 1. Minimal migration (\<25% wound coverage) 2. Moderate migration (25-75% coverage) 3. Extensive migration (\>75% coverage) (0-worse; 3-better)
Time frame: Baseline (Day 0), Day 5
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 0 | 18 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 1 | 12 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 2 | 7 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 3 | 3 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 0 | 0 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 1 | 4 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 2 | 8 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 3 | 28 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 3 | 9 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 0 | 24 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 0 | 6 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 1 | 10 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 2 | 10 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 2 | 4 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 5 of Post Application | Grade 1 | 15 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Neo-epithelialization | Day 0 / Baseline | Grade 3 | 2 Participants |
Primary
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) 1. Mild infiltration (5-10 vessels/hpf) 2. Moderate infiltration (11-20 vessels/hpf) 3. Abundant infiltration (\>20 vessels/hpf) (0-worse; 3-better)
Time frame: Baseline (Day 0), Day 5
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 0 | 0 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 0 | 11 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 1 | 2 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 2 | 8 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 2 | 7 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 3 | 6 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 3 | 31 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 1 | 15 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 3 | 8 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 0 | 17 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 1 | 14 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 3 | 3 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 0 | 4 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 1 | 13 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 5 Post Application | Grade 2 | 15 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Histopathological Parameters - Vascular Infiltration | Day 0 / Baseline | Grade 2 | 6 Participants |
Primary
Percent Change in Wound Area
Percent Change in Wound Area from week 1 through week 7 measured manually with digital photography
Time frame: 7 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Percent Change in Wound Area | -78.5 percentage change | Standard Deviation 18.2 |
| Dehydrated Human Amnion/Chorion Membrane | Percent Change in Wound Area | -65.1 percentage change | Standard Deviation 9.8 |
Secondary
Adverse Events
Adverse events (e.g., infection, allergic reactions)
Time frame: 6 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Adverse Events | No adverse event | 38 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Adverse Events | Mild Erythema | 2 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Adverse Events | Mild Allergic Reaction | 0 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Adverse Events | Severe adverse events | 0 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Adverse Events | Severe adverse events | 0 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Adverse Events | No adverse event | 34 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Adverse Events | Mild Allergic Reaction | 2 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Adverse Events | Mild Erythema | 4 Participants |
Secondary
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
Time frame: 7 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Complete Wound Closure Rates | 30 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Complete Wound Closure Rates | 25 Participants |
Secondary
Mean Number of Repeated Application
Mean number of reapplications of the HPTC & dHACM used to obtain wound closure over 6 Weeks
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Mean Number of Repeated Application | 0.85 mean number of reapplications | Standard Deviation 0.92 |
| Dehydrated Human Amnion/Chorion Membrane | Mean Number of Repeated Application | 1.15 mean number of reapplications | Standard Deviation 0.87 |
Secondary
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
Time frame: 7 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Patient Treatment Satisfaction | 4.33 score on a scale | Standard Deviation 0.62 |
| Dehydrated Human Amnion/Chorion Membrane | Patient Treatment Satisfaction | 3.41 score on a scale | Standard Deviation 0.78 |
Secondary
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
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Day 14 | 11.1 sqauare centimeters | Standard Deviation 2.4 |
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Day 28 | 7.0 sqauare centimeters | Standard Deviation 3.1 |
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Day 5 | 13.1 sqauare centimeters | Standard Deviation 2.3 |
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Day 35 | 5.2 sqauare centimeters | Standard Deviation 3.2 |
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Day 21 | 9.1 sqauare centimeters | Standard Deviation 2.8 |
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Day 42 | 3.2 sqauare centimeters | Standard Deviation 3.1 |
| High Purity Type-I Collagen-based Skin Substitute | Wound Size Progression Over Time | Baseline | 14.9 sqauare centimeters | Standard Deviation 2.1 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Day 42 | 5.2 sqauare centimeters | Standard Deviation 2.4 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Baseline | 15.0 sqauare centimeters | Standard Deviation 1.8 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Day 5 | 13.4 sqauare centimeters | Standard Deviation 2.1 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Day 14 | 11.5 sqauare centimeters | Standard Deviation 2.2 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Day 21 | 9.8 sqauare centimeters | Standard Deviation 2.1 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Day 28 | 8.2 sqauare centimeters | Standard Deviation 2.4 |
| Dehydrated Human Amnion/Chorion Membrane | Wound Size Progression Over Time | Day 35 | 6.8 sqauare centimeters | Standard Deviation 2.6 |
Other Pre-specified
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
Time frame: 7 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Purity Type-I Collagen-based Skin Substitute | Change in Quality of Life | Improvement | 29 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Change in Quality of Life | No Change | 11 Participants |
| High Purity Type-I Collagen-based Skin Substitute | Change in Quality of Life | Worsening | 0 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Change in Quality of Life | Improvement | 17 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Change in Quality of Life | No Change | 19 Participants |
| Dehydrated Human Amnion/Chorion Membrane | Change in Quality of Life | Worsening | 4 Participants |