PERCUTANEOUS TREATMENT OF PERIPHERAL ARTERIAL OCCLUSIVE DISEASE WITH IMPLANTATION OF MULTIPLE, BALLOON-EXPANDABLE, DRUG-ELUTING BIORESORBABLE SCAFFOLDS (the Efemoral Vascular Scaffold System)

通过植入多个可扩张球囊、药物洗脱生物可吸收支架（股动脉血管支架系统）经皮治疗外周动脉闭塞性疾病

• 批准号: 10545226
• 负责人: Lewis Schwartz
• 金额: $ 78.31万
• 依托单位: EFEMORAL MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545226
• 关键词: Acute; Affect; Age; Aging; American; Amputation; Arterial Occlusive Diseases; Arteries; Atherectomy; Balloon Angioplasty; Balloon Dilatation; Biochemical; Biology; Blood Circulation; Blood Vessels; Blood flow; Bypass; Cardiovascular Diseases; Characteristics; Chronic; Chronic Disease; Clinical; Clinical Research; Clinical Trials; Confusion; Congestive Heart Failure; Coronary; Coronary Arteriosclerosis; Development; Device Safety; Devices; Diagnosis; Dilatation - action; Disease; Drug Kinetics; Effectiveness; Enrollment; Environment; Epidemic; Excess Mortality; Failure; Family; Feasibility Studies; Foreign Bodies; Friends; Funding; Goals; Health; Human; Implant; International; Intervention; Ischemia; Kinetics; Lead; Left; Leg; Legal patent; Length; Lesion; Limb structure; Longevity; Lower Extremity; Mechanics; Medical; Metals; Mission; Modality; Morbidity - disease rate; Morphology; Motion; Operative Surgical Procedures; Outcome; Paclitaxel; Patient Care; Patients; Perfusion; Peripheral; Peripheral Vascular Diseases; Persons; Pharmaceutical Preparations; Phase; Plague; Population; Pre-Clinical Model; Preclinical Testing; Preparation; Prevalence; Privatization; Procedures; Process; Prognosis; Quality of life; Recurrence; Research Proposals; Safety; Small Business Innovation Research Grant; Stenosis; Stents; Surgeon; Surgical incisions; Survivors; Symptoms; System; Techniques; Technology; Therapeutic; Toxicology; United States; United States Food and Drug Administration; Vascular Diseases; antiproliferative drugs; biomaterial compatibility; clinical practice; cost; critical limb Ischemia; design; disability; experimental study; first-in-human; functional decline; healing; hospital readmission; implantation; limb loss; medical specialties; mortality; nitinol; novel; novel therapeutics; physical conditioning; pre-clinical; preclinical safety; preclinical study; premature; preservation; prototype; radiologist; restenosis; restoration; scaffold; skeletal; standard of care; symptom treatment; treatment choice; virtual

Cardiovascular disease is a tremendous burden on human health and longevity; by the year 2030, over 400 million people will have the disease including an annual mortality of more than 23 million. Vascular disease affecting the lower extremity arteries, known as “peripheral arterial occlusive disease” (PAOD), is an epidemic affecting approximately 10% of the population over the age of 50 and 20% of the population over the age of 70. Its prevalence is increasing at an alarming rate, by more than 20% over the last decade. Symptomatic PAOD causes loss of mobility, poor physical health, decreased quality of life, premature decline and early mortality. The physical burden of PAOD is greater than having congestive heart failure and the long-term prognosis is worse than having coronary artery disease. An estimated 11% of patients afflicted with PAOD have the most severe form of the disease: critical limb ischemia (CLI). CLI occurs when the occlusive lesions of PAOD have become so numerous and severe that the baseline perfusion of the extremity is inadequate to sustain its viability. It carries a dismal prognosis; only about half of affected patients will be alive with viable limbs only six months after the diagnosis is made. The standard-of-care for patients with symptomatic PAOD is percutaneous peripheral intervention (PPI) including the techniques of balloon angioplasty, drug-coated balloon angioplasty, percutaneous atherectomy, and bare and drug-eluting self-expanding stenting. Unfortunately, the effectiveness and durability of available devices is limited as up to 50% of conventional endovascular procedures will be complicated by arterial restenosis and recurrence within the first year. This research proposal describes the development of novel, serial, balloon-expandable, resorbable, drug-eluting scaffold designed to provide more immediately effective and durable endovascular treatment of symptomatic femoropopliteal occlusive disease. Unlike most peripheral intravascular devices that are simply adaptations and “scale-ups” of coronary devices, the Efemoral Vascular Scaffold System (EVSS) is specifically designed for the unique environment of the peripheral vasculature. Its design exploits known principles of vascular biology including that, (1) a rigid device that is deployed via balloon expansion represents the optimal design of an intravascular stent given its transient effect on the arterial wall and relative ease of precise implantation, (2) a long, rigid device cannot be safely implanted in an artery that bends and twists with skeletal motion, (3) long arteries that bend and twist could be effectively treated with multiple, short stents that allow the intervening, non-stented arterial segments to move unencumbered, (4) the length, number and spacing of the stent segments could be determined by the known bending characteristics of the target arteries, and (5) arteries need only be scaffolded transiently; late dissolution of the stent will facilitate long-term arterial healing and avoid the late complications of an indwelling foreign body. Efemoral Medical, Inc., was founded in 2015 with the mission of developing a novel, balloonexpandable, resorbable, drug-eluting scaffold designed to provide more simple, effective and durable endovascular treatment of symptomatic femoropopliteal occlusive disease. The Efemoral Vascular Scaffold System (EVSS) is a cheap and easily-manufactured biocompatible device that is prepared and deployed in an identical manner to simple angioplasty balloons. Private funding from vascular surgeons, interventional radiologists, interventional cardiologists, independent investors, friends and family established Efemoral Medical, Inc. as a going concern and developed the device through its design, prototype, biochemical, mechanical, toxicologic and pre-clinical proof-of-concept phases. A first-in-human, early feasibility, international clinical trial has enrolled six patients with good results. The purpose of this Direct Phase II SBIR proposal is to demonstrate the pre-clinical safety and efficacy of the Efemoral Vascular Scaffold System (EVSS) in preparation for initiation of a clinical Early Feasibility Study (EFS) in the United States. It’s Specific Aims are, (1) To demonstrate long-term device safety and efficacy in a GLP pre-clinical model of percutaneous peripheral vascular intervention, (2) To quantify device elution, mural drug transfer, systemic exposure and pharmacokinetic profile in a GLP pre-clinical model of percutaneous peripheral vascular intervention, and (3) To quantify the kinetics of scaffold dissolution in a GLP pre-clinical model of percutaneous peripheral vascular intervention.

心血管疾病是人类健康和寿命的巨大伯宁。到2030年，超过400年 百万人将患有这种疾病，包括年死亡率超过2300万。血管疾病 影响下肢动脉，称为“周围动脉闭塞性疾病”（PAOD），是一种流行病 在70岁以上的50％和20％的人口中，约有10％的人口。 在过去的十年中，它的患病率正在以惊人的速度增加，超过20％。有症状的PAOD 导致移动性丧失，身​​体健康不良，生活质量降低，过早下降和早期死亡率。 PAOD的身体灼伤比充血性心力衰竭更大，长期预后是 比患冠状动脉疾病还要糟糕。估计患有PAOD的患者中有11％的患者最多 疾病的严重形式：临界肢体缺血（CLI）。当PAOD的闭塞病变具有 变得如此众多和严重，以至于末端的基线灌注不足以维持其 生存能力。它带来了一个令人沮丧的提示；只有大约一半的患者将活着，只有六个 诊断后的几个月。 有症状PAOD患者的护理标准是经皮外周干预（PPI） 包括球囊血管成形术，药物涂覆的气球血管成形术，经皮动脉切除术的技术， 以及裸露和洗脱的自我膨胀支架。不幸的是，可用的有效性和耐用性 设备受到限制，因为多达50％的常规血管内手术会因动脉而复杂 第一年的再狭窄和复发。该研究建议描述了新颖的发展， 串行，膨胀，可吸收，洗脱脚手架，旨在提供更有效的 以及对有症状的股骨闭塞性疾病的持久血管内治疗。 与大多数仅是适应和冠状动脉的“扩大”的外围性血管内设备不同 设备，Efmoral血管支架系统（EVSS）是专门为独特环境而设计的 外围脉管系统。它的设计利用了血管生物学的已知原理，包括（1）刚性 通过气球扩展部署的设备代表了血管内支架的最佳设计 瞬态对动脉壁的影响和相对易于精度植入的影响，（2）长而刚性的装置不能是 安全地在动脉弯曲和骨骼运动曲折的动脉中实施，（3）弯曲和扭曲的长动脉 可以用多个短支架有效地处理，以允许中间的，不固定的人工制品 为了不受限制，（4）支架段的长度，数字和间距可以由 目标动脉的已知弯曲特性和（5）动脉只需要瞬时脚手架；晚的 支架的溶解将促进长期的动脉愈合，并避免留置晚期并发症 异物。 Efemoral Medical，Inc。成立于2015年，其使命是开发一种可扩展，可吸收，吸毒的脚手架的小说，旨在提供更简单，有效和耐用的脚手架 有症状的股骨闭塞性疾病的血管内治疗。厄运血管支架 系统（EVSS）是一种便宜且易于制造的生物相容性设备，已准备并部署在 与简单的血管成形术气球相同的方式。血管外科医生的私人资金，介入 放射科医生，介入心脏病专家，独立投资者，朋友和家人建立了Efemoral Medical，Inc。作为一个持续的关注，并通过其设计，原型，生化， 机械，毒理学和临床前概念验证阶段。第一个人类，早期可行性， 国际临床试验已招收六名效果良好的患者。 该直接II期SBIR提案的目的是证明临床前的安全性和效率 eformoral血管支架系统（EVSS）为启动临床早期可行性研究做准备 （EFS）在美国。它的具体目的是：（1）证明在 经皮外周血管干预的GLP临床前模型，（2）量化装置洗脱，壁画 在经皮的GLP临床前模型中，药物转移，全身暴露和药代动力学特征 周围血管干预，（3）量化GLP前临床前脚手架溶解的动力学 经科外周血管干预的模型。