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

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可单独发生，可与二尖瓣相关，也可与主要心脏畸形相关。在出生时患有先天性心脏病的8/1000(4-6/10,000)儿童中，CoA占5-8%。大多数CoA是在儿童时期新诊断的；其中25%的患者超过10岁。CoA大多在儿童时期通过手术或球囊导管扩张来修复。复发率从5%到10%不等。复发通常要到青春期或以后才能被发现。在美国和欧洲，导管输送球囊可扩张支架已经成为这个年龄段的CoA复发和新诊断的CoA的主要治疗方法；然而，还没有FDA批准的支架用于主动脉。大直径胆道支架目前用于这一过程的标签外。用于CoA的裸金属Cheatham白金支架(CPS)的关键试验正在进行中。主动脉缩窄支架试验(COSTART)旨在确认CPS对未经治疗和复发的CoA的安全性和有效性，并获得FDA对该适应症的批准。 裸露金属CPS的批准将有助于治疗患有这种疾病的患者，但在一些情况下，一些患者在裸露金属支架植入过程中会面临主动脉壁损伤的高风险。在裸金属支架置入术中，极度狭窄、遗传性主动脉壁无力和高龄都是使患者面临损伤风险的情况。患者也可能出现与先前的CoA修复相关的主动脉壁损伤(动脉瘤)。手术修复后的复发率为3-4%，球囊扩张后复发率为6-20%。这种动脉瘤的修复在外科手术上是具有挑战性的。对于这些患者，使用织物覆盖的Cheatham铂支架预防或修复主动脉壁损伤已成为欧洲和最近美国的首选治疗方法，FDA批准对覆盖的CPS进行同情使用。在美国，没有可用的替代设备。 这项拟议的试验将测试覆盖CPS修复或预防CoA相关的主动脉壁损伤的安全性和有效性。之前没有手术或插管试验来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，因为患者可能会接受任何一种适应症的设备。因此，根据一个儿科心脏病专家小组的临床判断，为这项试验制定了三类疾病严重程度量表(SIS)。它经过了海岸数据和安全监测委员会(DSMB)和FDA设备评估办公室的审查。这三种疾病包括：1)上肢血压水平，2)上下肢压差程度，3)主动脉壁损伤严重程度。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个的疾病级别。Dsmb将在基线和一年的随访中为每个患者分配一个严重程度，以进行比较。至少一个水平的改善是为了表明临床重要性。安全性的评估是通过识别不良事件并将其发生与医学文献中报道的相似年龄段的无并发症CoA的外科修复进行比较来进行的。

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.