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: 8286018
• 负责人: RICHARD ELLIOT RINGEL
• 金额: $ 39.58万
• 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/8286018
• 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，会阻碍主动脉血流。 CoA 可以单独发生，也可以与二叶式主动脉瓣或主要心脏畸形相关。 在 8/1000 (4-6/10,000) 出生时患有先天性心脏病的儿童中，CoA 占 5-8%。 大多数 CoA 是在儿童时期新诊断出来的；这些患者中 <25% 的年龄超过 10 岁。 CoA 主要在儿童时期通过手术或球囊导管扩张来修复。复发率范围为 5-10%。复发通常要到青春期或更长时间才被发现。在美国和欧洲，导管输送球囊扩张支架已成为该年龄段 CoA 复发和新诊断 CoA 的主要治疗方法；然而，FDA 还没有批准用于主动脉的支架。 目前，大直径胆道支架已在标签外用于此手术。 用于 CoA 的裸金属 Cheatham 铂支架 (CPS) 的关键试验正在进行中。 主动脉缩窄支架试验 (COAST) 旨在确认 CPS 对于未经治疗和复发的 CoA 的安全性和有效性，并获得 FDA 对该适应症的批准。 裸金属 CPS 的批准将有助于治疗患有这种疾病的患者，但有些患者在裸金属支架置入期间面临主动脉壁损伤的高风险。 极度狭窄、遗传性主动脉壁薄弱和高龄是使患者在裸金属支架植入期间面临受伤风险的例子。 患者还可能出现与先前 CoA 修复相关的主动脉壁损伤（动脉瘤）。 CoA 手术修复后的复发率为 3-4%，CoA 球囊扩张后的复发率为 6-20%。 修复此类动脉瘤在手术上具有挑战性。 对于这些患者，使用织物覆盖的 Cheatham 铂金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 的同情使用而成为首选治​​疗方法。 美国没有可用的替代设备。 这项拟议的试验将测试 Covered CPS 修复或预防与 CoA 相关的主动脉壁损伤的安全性和有效性。 之前没有手术或导管插入试验描述这种疗法的结果，因此没有比较的基础。 单一的结果评估是不够的，因为患者可能会收到针对任一适应症的设备。 因此，根据儿科心脏病专家小组的临床判断，为本试验制定了三级疾病严重程度量表（SIS）。 它由 COAST 数据和安全监测委员会 (DSMB) 和 FDA 设备评估办公室进行了审查。 三种疾病类别包括：1) 上肢血压水平，2) 上下肢压力差程度，以及 3) 主动脉壁损伤的严重程度。 已经定义了五个严重程度级别，并将用于分配三个类别中每一类别的疾病级别。 DSMB 将在基线和一年随访时为每位患者分配严重程度，以进行比较。 至少提高一个水平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道的相似年龄组的简单 CoA 手术修复的发生率进行比较来评估安全性。