A comparative efficacy study: treatments of non-healing diabetic foot ulcers

比较疗效研究：治疗不愈合的糖尿病足溃疡

基本信息

批准号：
8768441
负责人：
Roslyn Rivkah ISSEROFF
金额：
--
依托单位：
VA NORTHERN CALIFORNIA HEALTH CARE SYS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-10-01 至 2016-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8768441
关键词：
Address Adult Affect Amputation Apligraf Biological Biological Markers Biomedical Engineering Biometry Blood Vessels California Caring Cells Chronic Clinic Clinical Clinical Research Clinical Trials Control Groups Cost Analysis Debridement Devices Diabetes Mellitus Diabetic Foot Diabetic Foot Ulcer Diabetic ulcer Effectiveness Elements Enrollment Extracellular Matrix FDA approved Fibroblasts Foot Ulcer Genetic Goals Healed Health Health Care Costs Health Expenditures Healthcare Healthcare Systems Home environment Immunologics Improve Access Incidence Individual Infection Life Limb structure Living Costs Marketing Mind Morbidity - disease rate Neuropathy Operative Surgical Procedures Outcome Patient Care Patient Recruitments Patients Peripheral arterial disease Pharmaceutical Preparations Physicians Population Predisposition Randomized Randomized Clinical Trials Randomized Controlled Clinical Trials Reporting Savings Scientist Single-Blind Study Site Skin Substitutes System Temperature Testing Tissue Engineering Tissues Ulcer Weight-Bearing state Work Wound Healing angiogenesis arm base comparative efficacy cost cost effective cytokine diabetic diabetic wound healing effective therapy experience extracellular foot healing improved keratinocyte new growth patient population secondary outcome standard of care treatment duration wound

Address Adult Affect Amputation Apligraf Biological Biological Markers Biomedical Engineering Biometry Blood Vessels California Caring Cells Chronic Clinic Clinical Clinical Research Clinical Trials Control Groups Cost Analysis Debridement Devices Diabetes Mellitus Diabetic Foot Diabetic Foot Ulcer Diabetic ulcer Effectiveness Elements Enrollment Extracellular Matrix FDA approved Fibroblasts Foot Ulcer Genetic Goals Healed Health Health Care Costs Health Expenditures Healthcare Healthcare Systems Home environment Immunologics Improve Access Incidence Individual Infection Life Limb structure Living Costs Marketing Mind Morbidity - disease rate Neuropathy Operative Surgical Procedures Outcome Patient Care Patient Recruitments Patients Peripheral arterial disease Pharmaceutical Preparations Physicians Population Predisposition Randomized Randomized Clinical Trials Randomized Controlled Clinical Trials Reporting Savings Scientist Single-Blind Study Site Skin Substitutes System Temperature Testing Tissue Engineering Tissues Ulcer Weight-Bearing state Work Wound Healing angiogenesis arm base comparative efficacy cost cost effective cytokine diabetic diabetic wound healing effective therapy experience extracellular foot healing improved keratinocyte new growth patient population secondary outcome standard of care treatment duration wound

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项目摘要

DESCRIPTION (provided by applicant): Chronic, non-healing ulcers of the feet are common complications of adults with diabetes, occurring in about 15-20% of diabetics, and often leading to foot amputation. The resulting diabetic foot ulcers (DFU) and subsequent amputations generate significant patient morbidity and millions of dollars of health care expenditures. Even with the best standard of care, which is debridement of non-viable tissue, off-loading of weight-bearing and treatment of infection, only 30% of diabetic foot ulcers can be expected to heal within a 20 week treatment period. There is clearly an unmet need for better and more effective treatments to improve healing of these ulcers. New therapies are limited, but among them are bioengineered skin substitutes that incorporate elements of an extracellular matrix that is proposed to encourage angiogenesis and in-growth of new tissue, along with living cells, to generate the cytokines needed for wound repair. However the cost of engineered tissue can be staggering: $1,800 per application, and 8 applications required-to achieve the 50% healing rate noted in the clinical trials. We note that other biological tissues have also been shown to be effective in improving the rate of healing of diabetic ulcers, and these tissues, devoid of living cells and simpler to prepare for use, have also been found to be effective in healing ulcers with reported similar increased rates compared to standard of care. These non-cellular tissues however, are orders of magnitude cheaper than bioengineered tissues. We hypothesize that there is no difference in efficacy between these two product types, and that using the less expensive matrix could save our health care system millions of dollars without compromising patient health. Our goal in this proposal is to test this hypothesis using a randomized clinical trial. We propose a randomized, single blinded, clinical trial with four arms: standard of care, standard of care plus Dermagraft(R) (bioengineered extracellular matrix containing living fibroblasts), standard of care plus Apligraf(R) (bioengineered extracellular bilayered matrix containing living keratinocytes and fibroblasts), standard of care plus Oasis(R) (Healthpoint, Ltd.), extracellular matrix devoid of living cells in patients with non-healing diabetic foot ulcers. We plan to determine: Specific Aim 1: Effectiveness of each treatment arm in achieving the primary endpoint of wound closure at 12 weeks and secondary outcomes of complete closure at 20 weeks, and rate of healing in each treatment arm. Specific Aim 2: Cost analysis to determine which bioengineered extracellular matrix for the treatment of diabetic foot ulcers is most cost effective in reducing healthcare costs. Specific Aim 3: The genetic signature of non-healing vs. healing diabetic ulcers to identify biomarkers predictive for a wound that will heal within 12-20 weeks of treatment. Our work could provide not only important savings to our health care system, but also improved access to limb and life saving therapies for healing DFU to millions of affected individuals.

描述（由申请人提供）：脚踏术的慢性非愈合溃疡是成年糖尿病的常见并发症，发生在约15-20％的糖尿病患者中，并且通常导致足部截肢。由此产生的糖尿病足溃疡（DFU）和随后的截肢会产生明显的患者发病率和数百万美元的医疗保健支出。即使有最佳的护理标准，即不可行的组织的清创，重量承重和感染的治疗，只有30％的糖尿病足溃疡只能在20周的治疗期内愈合。显然，对改善这些溃疡的愈合的更好，更有效的治疗方法显然没有满足。新疗法受到限制，但其中包括生物工程的皮肤替代品，其中包含了细胞外基质的元素，该元素旨在鼓励血管生成和新组织的生长以及活细胞增长，以产生伤口修复所需的细胞因子。但是，工程组织的成本可能会令人震惊：每次应用1,800美元，以及在临床试验中指出的50％治愈率所需的8个应用。我们注意到，其他生物组织也已被证明可以有效地提高糖尿病性溃疡的愈合率，并且这些组织（没有活细胞）和更简单的准备使用的组织也有效地有效地有效地治愈了与标准护理标准相比，据报道具有相似的增加速率。但是，这些非细胞组织比生物工程组织便宜。我们假设这两种产品类型之间的功效没有差异，并且使用较便宜的矩阵可以节省我们的医疗保健系统，而不受损害患者健康的情况。我们在此提案中的目标是使用随机临床试验检验该假设。 We propose a randomized, single blinded, clinical trial with four arms: standard of care, standard of care plus Dermagraft(R) (bioengineered extracellular matrix containing living fibroblasts), standard of care plus Apligraf(R) (bioengineered extracellular bilayered matrix containing living keratinocytes and fibroblasts), standard of care plus Oasis(R) （HealthPoint，Ltd。），非疾病糖尿病足溃疡患者的细胞外基质。我们计划确定：具体目的1：每个治疗组在12周时闭合伤口的主要终点，并在20周时完全闭合的次要结果以及每个治疗组的愈合率。具体目标2：确定哪种生物工程的细胞外基质用于治疗糖尿病足溃疡，在降低医疗保健成本方面是最具成本效益的。特定目标3：非愈合与治愈糖尿病性溃疡的遗传特征，以识别可预测会在治疗后12-20周内愈合的伤口的生物标志物。我们的工作不仅可以为我们的医疗保健系统提供重要的节省，而且还可以改善获得肢体和挽救生命的疗法，以治愈数百万受影响的人。