Long-Term Observational Extension of Participants in the CREST-2 Randomized Clinical Trial

CREST-2随机临床试验参与者的长期观察延伸

• 批准号: 10688017
• 负责人: George Howard
• 金额: $ 75.35万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688017
• 关键词: Arterial Fatty Streak; Blinded; Blood Tests; Blood Vessels; Carotid Arteries; Carotid Atherosclerotic Disease; Carotid Endarterectomy; Carotid stent; Cessation of life; Clinic Visits; Clinical; Data; Detection; Devices; Effectiveness; Event; Funding; Health; Home; Hyperlipidemia; Hypertension; Informed Consent; Intention; Ipsilateral; Ischemic Stroke; Life; Longterm Follow-up; Measurement; Medical; Medical Records; Medicare; Methodology; Modeling; Modernization; Monitor; National Institute of Neurological Disorders and Stroke; Neurologic Deficit; Neurologist; North America; Participant; Patient Monitoring; Patients; Periodicals; Pharmaceutical Preparations; Population; Prevention trial; Procedures; Process; Randomized; Recruitment Activity; Relative Risks; Rest; Risk; Risk Factors; Risk Reduction; Sample Size; Sampling; Secure; Site; Stroke; Stroke prevention; Telephone; Testing; Therapeutic Intervention; Time; Titrations; Treatment Efficacy; Vascularization; Visit; Writing; atherosclerosis risk; beneficiary; clinical practice; cost effective; cost effectiveness; cost efficient; design; follow-up; hazard; improved; innovation; medication compliance; patient subsets; primary outcome; randomized, clinical trials; remote monitoring; restenosis; standard of care; stroke patient; stroke risk; study population; telehealth; treatment effect; treatment group; trial comparing; trial design; vascular risk factor; video visit

CREST-2 (clinicaltrials.gov number: NCT02089217) is a pair of parallel, actively recruiting procedural trials to prevent stroke comparing: 1) carotid endarterectomy (CEA) and intensive medical management (IMM) to IMM alone, and 2) carotid artery stenting (CAS) and IMM to IMM alone. CREST-2 is designed to have ≈3-year average follow-up (maximum, 4 years). 1,735 patients have been randomized as of 10/29/2020. CREST-2 IMM involves centralized iterative titration to maximum tolerated effect of medications to treat hypertension and hyperlipidemia. We have already demonstrated that CREST-2 IMM results in significant improvements in rates of vascular risk factor control. We propose a highly cost-efficient, centralized process involving telephone and telehealth visits and review of medical records to monitor for stroke endpoints and home health visits to monitor control of vascular risk factors after patients graduate from CREST-2 to assess rigorously the transferability and real-world long-term effectiveness of intensive medical management with or without carotid revascularization. Our proposed long-term observational extension (LOE) is significant regardless of the CREST-2 results. If revascularization fails to show superiority (i.e., if IMM-only treatment is superior or not significantly different), proponents of revascularization will argue that the average follow-up was not sufficiently long to document the benefit of the procedure. The intersection of risk curves in the Asymptomatic Carotid Atherosclerosis Study, which supported benefit of CEA compared to medical management, was noted at ≈2 years following study entry. Contemporary IMM likely pushes the point of intersection outward. If revascularization is shown to be superior in CREST-2, then the durability of the benefit of revascularization beyond the 3-year average follow-up will be questioned due to possible restenosis. We propose obtaining written informed consent on all CREST-2 patients for continued follow-up for an additional 5 years, providing a 7.5-year average follow-up, with a subset of patients followed to >10 years. Cost-effectiveness will be achieved through innovative follow-up methodology. Our approach is also designed to minimize patient burden and maximize retention. The primary aim of this proposal is estimation of post- procedure treatment differences between revascularization and IMM vs. IMM alone. The currently funded CREST-2 trial will provide data on post-procedure treatment differences up to ≈3 years. Extending follow-up will enable us to assess whether post-procedure benefit is maintained during intermediate (4-6 years) and long-term follow-up (7-10 years); thereby, testing durability. The primary outcome for the CREST-2 LOE is the composite of stroke and death within 44 days after randomization and ischemic stroke ipsilateral to the randomized vessel thereafter. Our LOE approach is significant because it can be applied to a wide variety of stroke prevention trials where the therapeutic intervention is a device or procedure.

CREST-2（临床trials.gov编号：NCT02089217）是一对相平行的，积极募集的程序试验，以防止中风比较：1）颈动脉内膜切除术（CEA）和密集型医疗管理（IMM）与INM单独使用，以及2）颈动脉支架（CAS）和INM IMM。 CREST-2的设计为约3年的平均随访（最大4年）。截至2020年10月29日，已有1,735名患者被随机分配。 Crest-2 IMM涉及集中迭代滴定，以最大程度地治疗高血压和高脂血症的药物。我们已经证明，CREST-2 IMM导致血管危险因素控制率的显着提高。我们提出了一个高昂的成本效率，集中式的过程，涉及电话和远程医疗访问以及对医疗记录的审查，以监控中风终点和家庭健康访问，以监控患者从CREST-2毕业后，以监控对血管危险因素的控制，以严格评估或不用Carotid carotid castascolarival的严格评估可转移性和现实世界中强大医疗管理的长期长期有效性。无论CREST-2结果如何，我们提出的长期观察扩展（LOE）都是重要的。如果血运重建未能表现出优势（即，如果仅由INM的治疗优势或没有显着差异），则血运重建的支持者将争辩说，平均随访不足以证明该程序的好处。研究进入后约2年时，指出了不对称颈动脉粥样硬化研究中风险曲线的相交，该研究支持了与医疗管理相比，该研究支持了CEA的益处。当代疫苗同样将交叉点向外推动。如果证明血运重建在CREST-2中是优越的，那么由于可能的再狭窄，血运重建的益处的持续时间将受到3年平均随访的持续时间。我们建议对所有CREST-2患者获得书面知情同意，以继续进行5年的持续随访，并提供7。5年的平均随访，其中一部分患者的次数为10年。成本效益将通过创新的后续方法来实现。我们的方法还旨在最大程度地减轻患者负担并最大化保留率。该提案的主要目的是估计血运重建与IMM与IMM之间的后期治疗差异。当前资助的CREST-2试验将提供有关最长约3年的后期治疗差异的数据。扩展随访将使我们能够评估中级（4 - 6年）和长期随访（7 - 10年）期间是否维持后期福利；因此，测试持续时间。 Crest-2 Loe的主要结果是在随机化后44天内的中风和死亡的综合和死亡的复合材料，此后与随机血管的缺血性相位。我们的LOE方法很重要，因为它可以应用于治疗干预是一种设备或程序的各种预防试验。