A Study Evaluating the Safety and Efficacy of Second-Generation Tissue Engineered Vascular Grafts (TEVG2)

评估第二代组织工程血管移植物 (TEVG2) 安全性和有效性的研究

基本信息

批准号：
10705412
负责人：
christopher Kane breuer
金额：
$ 37.59万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-11 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705412
关键词：
4D MRI Adopted Adoption Adverse event Age Angioplasty Angiotensin Receptor Animal Model Autologous Blood Circulation Blood Vessels Bone Marrow Cardiac Cardiac Surgery procedures Cause of Death Cells Child Clinical Clinical Research Clinical Trials Clinical Trials Design Common Ventricle Complication Computer Models Congenital Abnormality Congenital Heart Defects Coupled Data Development Devices Dose Echocardiography Electric Capacitance FDA approved Generations Growth Heart Ventricle Hospitals Implant Incidence Individual Inferior vena cava structure Institution Intervention Losartan Magnetic Resonance Imaging Measures Methods Modeling Monitor Mononuclear Morbidity - disease rate Multi-Institutional Clinical Trial Newborn Infant Operative Surgical Procedures Patients Performance Pilot Projects Postoperative Period Process Protocols documentation Pulmonary artery structure Reconstructive Surgical Procedures Repair Complex Research Design Resolution Safety Series Stenosis Structure System Technology Testing Time Tissue Engineering Translations Tubular formation Vascular Graft Work base clinical implementation confirmatory clinical trial congenital heart disorder cost design effective therapy experience graft function improved improved outcome infant outcome man mortality preclinical study prevent prospective rational design repaired scaffold surgery outcome vascular tissue engineering

项目摘要

PROJECT SUMMARY We developed a tissue engineered vascular graft (TEVG) designed specifically for use in congenital heart surgery. The TEVG is made by seeding autologous bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold. Once implanted the scaffold degrades and the TEVG transforms into a neovessel that resembles a native blood vessel both in structure and function. Results of the first FDA- approved clinical trial evaluating the use of the TEVG in children demonstrated that the TEVG is the first man- made vascular conduit that grows making it uniquely suited for use in the surgical repair of complex congenital heart defects, however; results of this study also demonstrated that incidence of stenosis was too high to recommend routine use of this promising technology. We subsequently developed an improved, second- generation TEVG that incorporates both rationally designed strategies for inhibiting the formation of TEVG stenosis and process improvement measures for assembling the TEVG, in addition to newer less stringent criteria for performing TEVG angioplasty. Herein we propose the next step in the development and translation of the TEVG: a single-institution, prospective, single-armed, exploratory-confirmatory clinical trial designed to evaluate the safety and efficacy of the second-generation TEVG in 24 patients over a 2-year period. In this study, we will evaluate the short-term (2 year) safety and efficacy of a second-generation TEVG for use as an extracardiac conduit in children with single ventricle cardiac anomalies undergoing modified Fontan surgery. We will serially monitor all graft recipients over a 2-year time course using echocardiography and MRI. We hypothesize that the second-generation TEVG will have a significantly lower incidence of critical stenosis compared to the results of original TEVG in our previous FDA-approved pilot study. In addition, we hypothesize that the TEVG will grow and transform over time into a highly compliant capacitance vessel. We will evaluate the effect of graft compliance on flow, turbulence, and power loss across the TEVG in the Fontan circulation. The development of a man-made vascular graft with growth capacity would enable the performance of definitive reconstructive surgical procedures at an early age and mitigate the need for additional surgeries due to somatic overgrowth (the process by which a child outgrows their implant), thereby improving outcomes in patients with congenital heart disease.

项目概要我们开发了一种专门用于先天性心脏病的组织工程血管移植物 (TEVG) 外科手术。 TEVG 是通过将自体骨髓来源的单核细胞接种到可生物降解的管状支架。一旦植入，支架就会降解，TEVG 会转变为在结构和功能上类似于天然血管的新生血管。第一次 FDA 的结果- 经批准的评估 TEVG 在儿童中使用的临床试验表明，TEVG 是第一个制造出可生长的血管导管，使其特别适合用于复杂先天性畸形的手术修复然而，心脏缺陷；这项研究的结果还表明，狭窄的发生率太高，无法建议常规使用这项有前途的技术。我们随后开发了一种改进的第二一代 TEVG，结合了合理设计的抑制 TEVG 形成的策略除了更新的不太严格的措施外，还采取了用于组装 TEVG 的狭窄和工艺改进措施进行 TEVG 血管成形术的标准。在此我们提出下一步的开发和翻译 TEVG：一项单机构、前瞻性、单组、探索性验证性临床试验，旨在在 24 名患者中评估第二代 TEVG 在 2 年时间内的安全性和有效性。在这个研究中，我们将评估第二代 TEVG 的短期（2 年）安全性和有效性，以用作接受改良 Fontan 手术的单心室心脏异常儿童的心外导管。我们将使用超声心动图和 MRI 在 2 年的时间内连续监测所有移植受者。我们假设第二代 TEVG 的严重狭窄发生率将显着降低与我们之前 FDA 批准的试点研究中原始 TEVG 的结果进行了比较。此外，我们假设随着时间的推移，TEVG 将成长并转变为高度兼容的电容容器。我们将评估移植物顺应性对 Fontan 循环中 TEVG 的流动、湍流和功率损失的影响。具有生长能力的人造血管移植物的开发将使在很小的时候就进行明确的重建手术，并减少由于其他原因而需要进行的额外手术体细胞过度生长（儿童生长超过植入物的过程），从而改善结果先天性心脏病患者。