A luminal vascular coating to reduce time to maturation and failures of AV-Fistulas for hemodialysis access

管腔血管涂层可减少血液透析通路中动静脉瘘的成熟时间和失败

基本信息

批准号：
8906287
负责人：
PRABIR ROY-CHAUDHURY
金额：
$ 85.08万
依托单位：
SYMIC BIOMEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-16 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8906287
关键词：
Accounting Acute Address Adhesions Adult American Animals Area Arteriovenous fistula Binding Biological Assay Blood Platelets Blood Vessels Blood flow Caliber Centers for Disease Control and Prevention (U.S.)Chemicals Chemistry Chronic Kidney Failure Chronic Toxicity Tests Clinic Clinical Clinical Research Clinical Trials Clinical Trials Design Collagen Development Dialysis procedure Doppler Ultrasound Drug Kinetics End stage renal failure Environment Europe Event Failure Family suidae Femoral vein Fistula Functional disorder Funding Healed Hemodialysis Hospitalization Hyperplasia Immunoassay In Vitro Incidence Infection Inguinal region Injury Lead Lesion Manufacturer Name Medicare Methods Morbidity - disease rate Parents Patients Pharmacodynamics Phase Phase I Clinical Trials Play Population Positioning Attribute Research Role Safety Saline Side Small Business Innovation Research Grant Speed Stenosis Technology Testing Therapeutic Thrombosis Time Toxicology Ultrasonography United States National Institutes of Health Veins Venous Work X-Ray Computed Tomography aging population cost femoral artery healing novel phase 1 study portion control prevent programs public health relevance

项目摘要

DESCRIPTION (provided by applicant): Research Area: This proposal addresses PHS 2014-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44]). More than 20 million American adults (1 in 10) have some level of chronic kidney disease (CDC), with a growing incidence in the aging population. Nearly 400,000 ESRD patients receive some form of dialysis, with the vast majority of hemodialysis being performed in a clinic. One of the major causes of morbidity for the ESRD population is hemodialysis vascular access dysfunction, which is responsible for 20% of all hospitalizations for this population. Vascular access accounts for 7.5% of Medicare's spending on the ESRD programs, a total of over $1BB per year. In the past 3 decades, there have been no major advances in the field of hemodialysis vascular access, resulting in a huge unmet clinical need. Native arteriovenous fistula (AVF) is the preferred method of access for hemodialysis because of its low rates of infection and thrombosis once the fistula has fully matured. However, between 23-46% of AVF in Europe and the US have problems with early failure or failure to mature, resulting in a primary patency of only 60-65% at 1 year. Both early and late failures are characterized by vascular stenosis, and the classical histological lesion associated with all AVF failure is neointimal hyperplasia. While many factors play a role in the development of neointimal hyperplasia in an AVF, the extent of damage to the endothelial layer of a vessel has been directly related to the degree of neointimal hyperplasia that occurs. Symic is develop a novel treatment for use in vascular access, aimed at addressing the injury that occurs in the creation of the AV fistula. The localized luminal vascular coating, called DS-SILY, binds to exposed collagen, blocking platelet adhesion to the vessel wall and thus inhibiting the initiating events in thrombosis and neointimal hyperplasia. In the Phase I portion of this work, Symic showed that delivery of DS-SILY to a newly formed fistula significantly increases the diameter of the fistula vein to 3 times the diameter of saline treated controls. Here we will correlate these increased diameters with increased flow rates to confirm that these fistulas are properly maturing for hemodialysis access. Additionally work includes the proper manufacturing controls and safety and toxicology studies necessary to move DS-SILY into early clinical work. Successful completion of this project will lead to the clinical development of a novel therapy to reduce the incidence of failure in vascular access for hemodialysis patients.

描述（由申请人提供）：研究领域：本提案涉及 NIH、CDC、FDA 和 ACF 的 PHS 2014-02 小型企业创新研究补助金申请综合征集（母版 SBIR [R43/R44]）。美国成年人（十分之一）患有一定程度的慢性肾病 (CDC)，并且在老龄化人口中发病率不断上升，接近 400,000 人。 ESRD 患者接受某种形式的透析，其中绝大多数血液透析是在诊所进行的，ESRD 人群发病的主要原因之一是血液透析血管通路功能障碍，占该人群所有住院治疗的 20%。血管通路占 Medicare 在 ESRD 项目上的支出的 7.5%，每年总计超过 1BB。在过去 30 年中，该领域没有取得重大进展。血液透析血管通路，导致巨大的未满足的临床需求，自体动静脉瘘（AVF）是血液透析的首选方法，因为一旦瘘管完全成熟，其感染和血栓形成率较低。欧洲和美国的 AVF 存在早期失败或未能成熟的问题，导致 1 年时的主要通畅率仅为 60-65%，早期失败和晚期失败的特点是。血管狭窄，与所有 AVF 失败相关的典型组织学病变是新生内膜增生。虽然许多因素在 AVF 新生内膜增生的发生过程中发挥作用，但血管内皮层的损伤程度与血管内皮层的损伤程度直接相关。 Symic 正在开发一种用于血管通路的新型治疗方法，旨在解决 AV 瘘管形成过程中发生的损伤。血管涂层，称为 DS-SILY，与暴露的胶原蛋白结合，阻止血小板粘附到血管壁，从而抑制血栓形成和新内膜增生的起始事件。新形成的瘘管显着增加了瘘管静脉的直径，达到生理盐水处理对照直径的 3 倍。在这里，我们将这些增加的直径与增加的流速相关联，以确认这些瘘管已经适当成熟。血液透析通路的其他工作包括将 DS-SILY 纳入早期临床工作所需的适当的生产控制以及安全性和毒理学研究，该项目的成功完成将导致新疗法的临床开发，以减少血管通路失败的发生率。对于血液透析患者。