Carotid Revascularization Endarterectomy vs. Stenting Trial: Long Term Follow-up

描述(由申请人提供)：这是颈动脉内膜切除术与支架植入试验(CREST)的竞争性更新，旨在确定颈动脉内膜切除术(CEA)与颈动脉支架植入(CAS)的相对疗效。在最初的资助期间，我们已经成功地完成了预先指定的2522名参与者的登记工作。预计平均随访2.8年的围术期和中期结果将在2010年2月或更早的时候报告。CREST的初步结果、ICSS的初步结果的公布以及包括Sapphire、EVA-3S和SPACE在内的其他血管重建试验的结果将为指导2至4年的颈动脉治疗提供可靠的“1A级”证据。这与接受CEA和CAS手术后活了几十年的患者形成了鲜明对比。研究的时间范围和患者可能受益的持续时间之间的不一致造成了真正缺乏证据的知识鸿沟。在这次竞争性续签中，我们寻求资金，以便继续监测这些参与者5年，并有可能进行长达10年的跟踪。我们的主要目标是将CREST队列的随访延长到4年以上，并评估CEA与CAS在术后6至10年预防同侧卒中方面的相对有效性。次要目标将1)评估是否有影响两种手术长期耐久性的因素，如年龄、性别、术前狭窄程度和症状状态，2)评估两种手术的相对有效性是否存在时间变化或模式，3)评估不同组之间再狭窄或血管重建率的差异，4)将符合Medicare资格的CREST参与者与住院和门诊CMS数据文件联系起来，以评估患者的结果和医疗服务的利用，5)收集可用随机受试者的DNA，用于未来对血运重建反应的遗传决定因素的研究。我们计划延长现有2522名登记每年就诊并有中点电话联系的患者的随访时间，从初步结果报告时的平均2.8年延长至平均7.5年，最长随访时间为10年。通过延长的随访，对主要目标的统计分析将评估术后第31天至10年的治疗差异，旨在提供90%的能力来检测1.67的危险比。随着对临床结果的长期跟踪的关注，跟踪方案的简化将导致患者/临床负担的减轻、成本的降低和数据质量的提高。预计CREST的长期结果将对管理症状性和无症状性颈动脉狭窄的护理标准产生改变实践的影响。

DESCRIPTION (provided by applicant): This is a competitive renewal for the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) that is designed to establish the relative efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS). During the initial funding period we have successfully completed enrollment of our pre-specified cohort of 2522 participants. Peri-procedural and mid-term outcomes, over a projected mean follow-up of 2.8 years, will be reported in February of 2010 or earlier. The primary results from CREST, publication of the primary results from ICSS, and the results of other revascularization trials including SAPPHIRE, EVA-3S, and SPACE will provide solid "Level 1A" evidence to guide carotid treatment over a 2 to 4 year time horizon. This is in contrast to patients living decades after CEA and CAS have been performed. The discordance between the time horizons of studies and the duration that patients may benefit creates a knowledge gap where there is a true dearth of evidence. In this competitive renewal we seek funding to continue to monitor these participants for an additional 5 years, with the potential for follow-up of up to 10 years. Our Primary Aim is to extend follow-up of the CREST cohort beyond 4 years and to assess the relative efficacy of CEA versus CAS over the 6 to 10 year post-procedural period in the prevention of ipsilateral stroke. Secondary aims will 1) assess if there are effect modifiers of the long-term durability of the two procedures, such as age, sex, pre-operative degree of stenosis and symptomatic status, 2) assess if there is a temporal change or pattern in the relative efficacy of the two procedures, 3) assess differences between groups in the rates of restenosis or revascularization, 4) link Medicare-eligible CREST participants with inpatient and outpatient CMS data files to assess patient outcomes and utilization of healthcare services, 5) collect DNA on available randomized subjects for future studies of genetic determinants of response to revascularization. We plan to extend follow-up of the existing 2522 enrolled with annual clinic visits interspersed with midpoint telephone contacts, from an average 2.8 years at the time of primary outcome reporting to an average 7.5 years, with a maximum follow-up of 10 years. With extended follow-up, statistical analysis of the primary aim will assess post-procedural treatment differences from Day 31 for up to 10 years of follow-up and is designed to provide 90% power to detect a hazard ratio of 1.67. With the focus of long-term follow-up on clinical outcomes, simplification of the follow-up protocol will result in reduced patient/clinic burden, reduced cost, and improved data quality. It is anticipated that CREST long-term results will have practice-changing implications regarding the standard of care for managing symptomatic and asymptomatic carotid arterial stenosis.