Phase 2/3 of Covered Cheatham Platinum Stent for Aortic Wall Injury

用于治疗主动脉壁损伤的 Cheatham 铂金覆膜支架的 2/3 期

• 批准号: 8512666
• 负责人: RICHARD ELLIOT RINGEL
• 金额: $ 39.55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-22 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512666
• 关键词: Phase; Covered; Cheatham; Platinum; Stent

DESCRIPTION (provided by applicant): Coarctation of the aorta (CoA) is a congenital abnormality producing obstruction to blood flow through the aorta. CoA can occur in isolation, in association with bicuspid aortic valve, or with major cardiac malformations. CoA accounts for 5-8% of the 8/1000 (4-6/10,000) children born with congenital heart disease. Most CoA is newly diagnosed in childhood; <25% of these patients are recognized beyond 10 years of age. CoA is mostly repaired in childhood by surgery or alternatively by balloon catheter dilation. Recurrence rates range from 5-10%. Recurrence is often not recognized until adolescence or beyond. In the US and Europe, catheter-delivered balloon expandable stents have become the predominant therapy for CoA recurrence and new diagnoses of CoA in this age group; however, there are no FDA approved stents for use in the aorta. Large diameter biliary stents are currently used off label for this procedure. Enrollment into the pivotal trial of bare metal Cheatham Platinum Stents (CPS) for use in CoA is ongoing. The Coarctation of the Aorta Stent Trial (COAST) aims to confirm safety and efficacy of the CPS for untreated and recurrent CoA and achieve FDA approval for this indication. Approval of bare metal CPS will help treat patients who have this condition, but there are conditions that place some patients at high risk of aortic wall injury during bare metal stenting. Extreme narrowing, genetic aortic wall weakness, and advanced age are examples of conditions that place patients at risk of injury during bare metal stenting. Patients may also present with aortic wall injury (aneurysm) related to a prior CoA repair. Recurrence after surgical repair of CoA is 3-4% and following balloon dilation of CoA is 6-20%. Repair of such aneurysms is surgically challenging. For these patients, use of fabric-covered Cheatham Platinum Stents to either prevent or repair aortic wall injury has become the treatment of choice in Europe and recently in the USA through FDA-approved Compassionate Use of the Covered CPS. There are no alternative devices available in the US. This proposed trial will test safety and efficacy of Covered CPS to repair or prevent aortic wall injury associated with CoA. There are no prior surgical or catheterization trials describing outcomes for this therapy and thus, no basis for comparison. A single outcome assessment will not suffice since patients might receive a device for either indication. Thus, a three-category Severity of Illness Scale (SIS) was developed for this trial, based on the clinical judgment of a panel of pediatric cardiologists. It was reviewed by the COAST Data and Safety Monitoring Board (DSMB) and FDA's Office of Device Evaluation. The three illness categories include: 1) Level of upper extremity blood pressure, 2) Degree of upper to lower extremity pressure difference, and 3) Severity of aortic wall injury. Five levels of severity have been defined and will be used to assign level of illness in each of the three categories. The DSMB will assign a level of severity for each patient at baseline and one year follow-up for comparison. Improvement by at least one level has been designed to indicate clinical importance. Safety is evaluated by identifying adverse events and comparing their occurrence to that for surgical repair of uncomplicated CoA in similar age groups as reported in the medical literature.

描述（由申请人提供）： 主动脉缩窄（CoA）是一种先天性异常，导致通过主动脉的血流受阻。 CoA可以单独发生，也可以与二叶主动脉瓣或主要心脏畸形相关。 CoA占先天性心脏病出生儿童8/1000（4-6/10，000）的5-8%。 大多数CoA是在儿童时期新诊断的; <25%的这些患者在10岁以上被发现。 CoA主要在儿童期通过手术或球囊导管扩张修复。复发率为5- 10%。复发往往直到青春期或以后才被发现。在美国和欧洲，导管输送球囊扩张支架已成为该年龄组CoA复发和新诊断CoA的主要治疗方法;然而，尚无FDA批准的用于主动脉的支架。 大直径胆道支架目前在该手术中标签外使用。 用于CoA的Cheatham Platinum裸金属支架（CPS）关键试验的入组正在进行中。 主动脉支架缩窄试验（COAST）旨在确认CPS治疗未经治疗和复发性CoA的安全性和有效性，并获得FDA对该适应症的批准。 批准裸金属CPS将有助于治疗患有这种疾病的患者，但有些情况会使一些患者在裸金属支架植入术期间面临主动脉壁损伤的高风险。 极端狭窄、遗传性主动脉壁薄弱和高龄是裸金属支架植入术期间患者存在损伤风险的情况。 患者还可能出现与既往CoA修复相关的主动脉壁损伤（动脉瘤）。 CoA手术修复后复发率为3-4%，CoA球囊扩张后复发率为6- 20%。 这种动脉瘤的修复在手术上具有挑战性。 对于这些患者，使用织物覆盖的Cheatham Platinum支架来预防或修复主动脉壁损伤已成为欧洲的首选治疗方法，最近在美国，通过FDA批准的覆盖CPS的兼容使用。 在美国没有可用的替代器械。 本拟定试验将测试Covered CPS修复或预防CoA相关主动脉壁损伤的安全性和有效性。 之前没有描述该疗法结局的手术或导管插入术试验，因此，没有进行比较的基础。 单一结局评估是不够的，因为患者可能会因任一适应症而接受器械。 因此，根据儿科心脏病专家小组的临床判断，为本试验开发了三类疾病严重程度量表（SIS）。 它由COAST数据和安全监测委员会（DSMB）和FDA器械评估办公室审查。 三种疾病类别包括：1）上肢血压水平，2）上肢与下肢压差程度，3）主动脉壁损伤严重程度。 已定义了五个严重程度级别，并将用于分配三个类别中每一个的疾病级别。 DSMB将在基线和1年随访时为每例患者指定一个严重程度水平，以进行比较。 至少一个水平的改善旨在表明临床重要性。 通过识别不良事件并将其发生率与医学文献中报告的相似年龄组中无并发症CoA的手术修复的发生率进行比较来评价安全性。