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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Percentage Wound Area Change
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Percentage Wound Area Change
时间窗: 7 Weeks
Percentage wound area change from week 1 through week 7 measured manually with digital photography
Histopathological Parameters - Vascular Infiltration
时间窗: 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) 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
时间窗: 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 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
时间窗: 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 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 - Capillary Density
时间窗: 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
Histopathological Parameters - Inflammatory Response
时间窗: 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 1. Mild chronic inflammation 2. Moderate mixed inflammation 3. Severe acute inflammation (0-worse; 3-better)
Histopathological Parameters - Collagen Deposition
时间窗: 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 1. Loose, immature collagen 2. Moderate organized collagen 3. Dense, mature collagen architecture (0-worse; 3-better)
次要结局
- 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)
研究者
Dr Naveen Narayan MS, MCh (Plastic Surgery)
Professor & HoD, Department of Plastic Reconstructive & Aesthetic Surgery
Adichunchanagiri Institute of Medical Sciences, B G Nagara