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: 10706525
• 负责人: Lewis Schwartz
• 金额: $ 119.3万
• 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/10706525
• 关键词: Acute; Affect; Age; Aging; American; Amputation; Arterial Occlusive Diseases; Arteries; Atherectomy; Balloon Angioplasty; Balloon Dilatation; Biochemical; Biology; Blood Vessels; Blood flow; Bypass; Cardiovascular Diseases; Characteristics; Chronic; Chronic Disease; Circulation; 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; 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; United States; United States Food and Drug Administration; Vascular Diseases; Vascularization; 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; manufacture; medical specialties; mortality; nitinol; novel; novel therapeutics; participant enrollment; physical conditioning; pre-clinical; preclinical efficacy; 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.

到 2030 年，心血管疾病对人类健康和寿命造成巨大负担； 数百万人将患有这种疾病，其中每年有超过 2300 万人死于血管疾病。 影响下肢动脉的疾病，称为“外周动脉闭塞性疾病”(PAOD)，是一种流行病 影响约10%的50岁以上人口和20%的70岁以上人口。 有症状的 PAOD 患病率正在以惊人的速度增加，在过去十年中增加了 20% 以上。 导致行动能力丧失、身体健康状况不佳、生活质量下降、过早衰退和过早死亡。 PAOD 的身体负担比充血性心力衰竭更大，长期预后较差 据估计，受 PAOD 影响的患者中，有 11% 的情况最严重。 该疾病的严重形式：当 PAOD 的闭塞性病变出现时，会发生严重肢体缺血 (CLI)。 变得如此数量和严重以至于四肢的基线灌注不足以维持其 它的预后很差；只有大约一半的患者能够存活，只有六个肢体。 做出诊断后几个月。 有症状 PAOD 患者的标准治疗是经皮外周介入治疗 (PPI) 包括球囊血管成形术、药物涂层球囊血管成形术、经皮斑块旋切术、 不幸的是，裸支架和药物洗脱自膨式支架的有效性和耐用性较差。 设备有限，因为高达 50% 的传统血管内手术会因动脉血管问题而变得复杂 第一年内的再狭窄和复发该研究提案描述了新颖的、 系列、球囊扩张、可吸收、药物洗脱支架，旨在提供更立即有效的效果 对有症状的股腘闭塞性疾病进行持久的血管内治疗。 与大多数外周血管内装置不同，这些装置只是冠状动脉的适应和“放大” 设备，股骨血管支架系统（EVSS）是专门为独特的环境而设计的 其设计利用了血管生物学的已知原理，包括：(1) 刚性的。 通过球囊扩张展开的装置代表了血管内支架的最佳设计，因为它的 对动脉壁的短暂影响和精确植入相对容易，(2) 长而刚性的装置不能 安全地植入随着骨骼运动而弯曲和扭转的动脉，(3) 弯曲和扭转的长动脉 可以使用多个短支架进行有效治疗，这些支架允许介入、无支架的动脉段 为了不受阻碍地移动，(4)支架段的长度、数量和间距可由下式确定： 已知目标动脉的弯曲特性，并且（5）仅需要在后期暂时搭建动脉支架； 支架的溶解将促进长期动脉愈合并避免留置的晚期并发症 异物。 Efemoral Medical, Inc. 成立于 2015 年，其使命是开发一种新颖的球囊可扩张、可吸收、药物洗脱支架，旨在提供更简单、有效和耐用的支架 有症状的股腘闭塞性疾病的血管内治疗。 系统（EVSS）是一种廉价且易于制造的生物相容性设备，可在 与简单的血管成形术球囊相同的方式来自血管外科医生的私人资助，介入治疗。 放射科医生、介入心脏病专家、独立投资者、朋友和家人共同创立了 Efemoral Medical, Inc. 作为一家持续经营企业，通过其设计、原型、生化、 机械、毒理学和临床前概念验证阶段。 国际临床试验已入组6名患者，效果良好。 该直接 II 期 SBIR 提案的目的是证明临床前安全性和有效性 股骨血管支架系统 (EVSS) 为启动临床早期可行性研究做准备 (EFS) 在美国的具体目标是，(1) 证明设备的长期安全性和有效性。 经皮周围血管介入治疗的GLP临床前模型，（2）量化器械洗脱、壁画 经皮 GLP 临床前模型中的药物转移、全身暴露和药代动力学特征 外周血管介入，以及 (3) 量化 GLP 临床前支架溶解的动力学 经皮外周血管介入治疗模型。

项目成果

Intravascular treatment of long segments of experimental peripheral arteries with multiple, serial, balloon-expandable, resorbable scaffolds.

• DOI: 10.1016/j.jvssci.2022.03.002
• 发表时间: 2022
• 期刊: JVS-vascular science
• 作者: El Khoury, Rym;Tzvetanov, Ivan;Estrada, Edward A;McCarroll, Edward;Michal, Eugene;Blumeyer, Jack;Guy, Louis-Georges;Laflamme, Martin;Schwartz, Lewis B
• 通讯作者: Schwartz, Lewis B