A Multicenter Randomized Controlled Trial of Surveillance versus. Endoscopic Therapy for Barretts Esophagus with Low-grade Dysplasia: The SURVENT Trial

监测与监测的多中心随机对照试验。

• 批准号: 10273769
• 负责人: VALERIE L DURKALSKI
• 金额: $ 220万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10273769
• 关键词: Achievement; Address; Adult; Affect; Area; Barrett Esophagus; Biological; Biological Markers; Biopsy; Caregivers; Caring; Chronic; Clinical; Clinical Management; Clinical Trials; Clinical Trials Data Monitoring Committees; Complication; Conduct Clinical Trials; Data; Detection; Diagnosis; Disease; Dysplasia; Effectiveness; Endoscopy; Enrollment; Ensure; Equipoise; Esophageal Adenocarcinoma; Esophageal mucous membrane; Esophagus; Europe; Feedback; Forcep; Funding; Future; Gastroesophageal reflux disease; Goals; Grant; Guidelines; Healthcare; High grade dysplasia; Histologic; Image; Immunohistochemistry; Incidence; Institute of Medicine (U.S.); Knowledge; Lead; Logistics; Malignant Neoplasms; Malignant neoplasm of esophagus; Metaplasia; Modality; Molecular; Morbidity - disease rate; Mucous Membrane; Patient Care; Patient-Focused Outcomes; Patients; Peer Review; Periodicity; Population; Positioning Attribute; Precancerous Conditions; Principal Investigator; Procedures; Protocols documentation; Public Health; Quality of life; Randomized; Randomized Controlled Trials; Research; Research Priority; Risk; Sample Size; Sampling; Specific qualifier value; Survival Rate; TP53 gene; Time; Translational Research; Treatment Cost; United States; Well in self; Work; arm; base; biobank; biomarker panel; clinical biomarkers; clinically relevant; cohort; common treatment; comparative effectiveness; comparative safety; compare effectiveness; cost; design; experience; follow-up; health related quality of life; high risk; improved; inclusion criteria; innovation; multidisciplinary; patient oriented; patient population; predict clinical outcome; primary endpoint; public health relevance; randomized trial; risk stratification; standard of care; treatment center; treatment group; tumor progression

Project Summary/Abstract Barrett's esophagus (BE), a metaplastic change of the esophageal lining associated with chronic gastroesophageal reflux disease, is the only known precursor to esophageal adenocarcinoma (EAC). EAC is one of the most rapidly increasing cancers in the United States, frequently presenting at an advanced stage and associated with a dismal 5-year survival rate. Endoscopic eradication therapy (EET) is the standard of care for patients with BE and high-grade dysplasia (HGD) or mucosal EAC. However, a central unresolved issue is whether BE patients with low-grade dysplasia (LGD) benefit from EET. The diagnosis of LGD is far more common than HGD and is associated with a lower risk of EAC, so it is unclear whether the costs and complications of EET are justified in this group of patients or whether they should simply continue with periodic surveillance endoscopy. The presence of clinical equipoise and the importance of this question indicates that a trial of endoscopic surveillance versus EET in this patient population is an urgent, unmet gap in our current knowledge regarding treatment of this common condition. We are uniquely positioned to address this significant gap in knowledge as we have assembled a multidisciplinary team with the requisite expertise in the conduct of clinical trials and biomarker research to ensure successful design and high-quality execution of the SURVENT trial (Surveillance versus Endoscopic Therapy for BE with LGD). This multicenter randomized controlled trial (n=530) will compare endoscopic surveillance and EET for the management of LGD using uniform inclusion criteria, design and endpoints. This trial will also include an observational cohort arm for those who decline randomization but are otherwise eligible (up to 150 subjects). Following our achievements during the U34 grant period, we propose the following aims for the U01: Specific Aim #1 will compare the two approaches using the primary endpoint of neoplastic progression rate (progression to HGD or mucosal or invasive EAC). Specific Aim #2 will compare patient-centered outcomes such as health-related quality of life between the two treatment groups. Specific Aim #3 will determine the utility of molecular (TissueCypher and p53 immunohistochemistry) and imaging (wide-area transepithelial sampling – WATS) biomarkers to improve risk-stratification in BE with LGD patients undergoing surveillance and EET. Biological samples will also be obtained at pre-specified time points to establish a biorepository for future translational research initiatives. The relevance of this work to the public health is high. BE is a common condition, affecting 2-3% of adult US population and LGD is seen in up to 40% of BE patients. This is a precursor for EAC and millions of dollars are spent yearly on the management of BE and EAC patients. The impact of our innovative study will include identifying the best patient-centered treatment approach for BE patients with LGD, which will inform the care of thousands of patients annually.

项目摘要/摘要 巴雷特的食管（BE），与慢性相关的食道衬里的化生变化 胃食管反射疾病是食管腺癌（EAC）唯一已知的先驱。 EAC是 美国经常出现在美国的癌症中最快的癌症之一 并与惨淡的5年生存率有关。内窥镜根除疗法（EET）是 护理BE和高级发育不良患者（HGD）或粘膜EAC。但是，一个未解决的中央 问题是EET是否有低度发育不良（LGD）受益的患者。 LGD的诊断远 比HGD更常见，并且与EAC的风险较低有关，因此尚不清楚成本和成本是否存在 在这组患者中，EET的并发症是合理的，或者他们是否应该继续定期继续 监视内镜。临床平衡的存在和这个问题的重要性表明 在该患者人群中，内窥镜监视与EET的试验在我们当前是紧迫的，未满足的差距 有关这种常见状况的治疗知识。我们在解决这个问题上很有位置 当我们汇集了一个具有必要专业知识的多学科团队时，知识的差距很大 进行临床试验和生物标志物研究，以确保成功设计和高质量执行 幸存试验（对LGD的监测与内窥镜治疗）。这个多中心随机 对照试验（n = 530）将比较使用LGD管理的内窥镜监视和EET 统一的纳入标准，设计和端点。该试验还将包括一个观察群 那些拒绝随机化但否则符合条件（最多150名受试者）的人。遵循我们的成就 在U34赠款期间，我们提出以下目标对U01：特定目标1将比较两者 使用肿瘤进展速率的主要终点（进展为HGD或粘膜或 入侵EAC）。特定的目标＃2将比较以患者为中心的结果，例如与健康相关的生活质量 在两个治疗组之间。特定的目标＃3将确定分子的效用（组织和 p53免疫组织化学）和成像（宽面积的transepiselial采样 - WATS）生物标志物可改善 LGD患者接受监视和EET的风险分层。生物样品也将是 在预先指定的时间点获得，以建立一个生物座位，用于未来翻译的研究计划。这 这项工作与公共卫生的相关性很高。是一个普遍的状况，影响2-3％的成人美国 多达40％的患者可见种群和LGD。这是EAC的先驱，数百万美元 每年用于管理BE和EAC患者的管理。我们创新研究的影响将包括 确定最佳患者以患者为中心的LGD患者，这将为您提供护理 每年成千上万的患者。