Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT )

腹主动脉瘤无创治疗临床试验（N-TA^3CT）

• 批准号: 9223638
• 负责人: BERNARD TIMOTHY BAXTER
• 金额: $ 138.85万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223638
• 关键词: Abdominal Aortic Aneurysm; Age; American; Aneurysm; Animal Model; Aorta; Basic Science; Biological Markers; Biology; Blood Vessels; Caliber; Cause of Death; Cessation of life; Clinical; Clinical Trials; Clinical Trials Design; Control Groups; Controlled Clinical Trials; Data; Data Analyses; Detection; Development; Double-Blind Method; Doxycycline; Early Diagnosis; Elderly; Enzymes; Failure; Family; Future; Gelatinase B; General Population; Geriatrics; Growth; Human; Image Analysis; Interferon Type II; Intervention; Laboratory Animal Models; Lead; Life; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Mechanics; Medical; Monitor; Natural History; Observational Study; Operative Surgical Procedures; Outcome; Patients; Perceived quality of life; Phase; Placebo Control; Placebos; Population; Populations at Risk; Production; Proteins; Public Health; Randomized; Research; Research Personnel; Risk; Rupture; Ruptured Aneurysm; Savings; Smooth Muscle Myocytes; Societies; Testing; Tetracyclines; Time; Tissues; Translating; Ultrasonography; Woman; X-Ray Computed Tomography; circulating biomarkers; clinical practice; cost effective; data management; effective therapy; follow-up; men; mortality; operation; prevent; prospective; repaired; safety testing; screening; treatment effect

DESCRIPTION (provided by applicant): Abdominal aortic aneurysms (AAA) are a common (2-5% of the population e 65 years: 4-9% men; 0.5- 1.5% women) and lethal problem causing 15,000 deaths annually from rupture in the U.S. The only accepted treatment is repair of the AAA which is performed for 40,000 large AAA annually in the U.S. With recent, widespread screening, many more small (<5.0 cm in men, <4.5 cm in women) AAA will be detected. The natural history of AAA is expansion to a size at which the risk of rupture greatly increases. There is no proven medical intervention that will prevent or delay this progression, and surgical options are expensive and unnecessarily risky for small aneurysms. There is experimental and clinical evidence that a family of matrix degrading proteins called matrix metalloproteinases (MMPs) are involved in initiation and progression of AAA. Recent evidence from laboratory, animal models and observational studies demonstrate that doxycycline, working as an MMP inhibitor, can prevent progression of AAA. In recent studies, doxycycline has been shown to: (1) inhibit the growth of experimental abdominal aortic aneurysms; (2) inhibit MMP production in aortic smooth muscle cells and in explanted aneurysm tissue; (3) reduce MMP expression in aneurysm tissue when patients are treated prior to operation for aneurysm repair; (4) reduce circulating MMP levels in AAA patients; (5) decrease the growth rate of small AAA in a limited clinical trial. We have demonstrated that doxycycline is well-tolerated in patients with small AAA. We will bring together investigators with expertise in vascular surgery, clinical trial design, data analysis and management, image analysis of AAA and analysis of circulating biomarkers that reflect aneurysm growth. We will test primary and secondary hypotheses and mechanisms of action related to whether or not doxycycline will inhibit (>40%) the growth of small (3.5 - 5.0 cm in men, 3.5 - 4.5 cm in women) infrarenal AAA. We will determine the effects of doxycycline on the expansion rate of small AAA over a 24-month period for all patients with allowance made for outcomes missing for cause (death or aneurysm repair) or undetermined reasons. This will be done through a prospective, double blind, placebo controlled clinical trial of 248 patients. Patients will be randomly assigned to receive placebo or doxycycline (100 mg bid). The primary end point will be aneurysm growth rate determined by semiannual CT scan. The public health impact of testing the safety and efficacy of doxycycline in the treatment of abdominal aortic aneurysms derives from the absence of any medical therapy to avoid open surgery or endograft repair. Without medical therapy, ultrasound screening is considered cost-effective in selected patients only. Effective medical therapy would make early detection even more acceptable by providing an alternative to invasive repair of AAA.

描述（由申请人提供）：腹主动脉瘤（AAA）是一种常见的（65岁以下人群中占2-5%，男性占4-9%，女性占0.5- 1.5%）致命问题，在美国每年因破裂导致15,000人死亡。唯一接受的治疗方法是修复AAA，美国每年有40,000例大型AAA进行修复。随着最近广泛的筛查，将发现更多的小型AAA（男性<5.0 cm，女性<4.5 cm）。AAA的自然历史是扩张到一个大小，破裂的风险大大增加。目前还没有证实的医学干预措施可以阻止或延缓这种进展，而且对于小动脉瘤来说，手术治疗既昂贵又有不必要的风险。有实验和临床证据表明，一种称为基质金属蛋白酶（matrix metalloproteinases, MMPs）的基质降解蛋白家族参与了AAA的发生和发展。最近来自实验室、动物模型和观察性研究的证据表明，强力霉素作为一种MMP抑制剂，可以预防AAA的发展。(2)抑制主动脉平滑肌细胞和外植动脉瘤组织中MMP的产生；(3)动脉瘤修复术前治疗可降低动脉瘤组织中MMP的表达；(4)降低AAA患者循环MMP水平；(5)在有限的临床试验中降低小AAA的生长速度。我们已经证明，多西环素在小型AAA患者中具有良好的耐受性。我们将汇集血管外科、临床试验设计、数据分析和管理、AAA图像分析和反映动脉瘤生长的循环生物标志物分析方面的专业人员。我们将检验与强力霉素是否会抑制（bbbb40 %）小型（男性3.5 - 5.0 cm，女性3.5 - 4.5 cm）肾下AAA生长有关的主要和次要假设和作用机制。我们将确定强力霉素对所有患者24个月期间小型AAA扩张率的影响，并考虑到因原因（死亡或动脉瘤修复）或未确定原因导致的结果缺失。这将通过对248名患者进行前瞻性、双盲、安慰剂对照的临床试验来完成。患者将被随机分配接受安慰剂或强力霉素（100mg bid）。主要终点为动脉瘤生长速率，由半年一次的CT扫描确定。测试强力霉素治疗腹主动脉瘤的安全性和有效性对公共卫生的影响源于没有任何药物治疗来避免开放手术或内移植物修复。在没有药物治疗的情况下，超声筛查被认为仅在选定的患者中具有成本效益。有效的药物治疗将使早期发现更容易被接受，因为它提供了一种替代侵入性修复AAA的方法。

项目成果

Clinical characteristics associated with readmission among patients undergoing vascular surgery.

接受血管手术的患者与再入院相关的临床特征。

• DOI: 10.1016/j.jvs.2013.10.103
• 发表时间: 2014
• 期刊: Journal of vascular surgery
• 影响因子: 4.3
• 作者: Engelbert,TravisL;Fernandes-Taylor,Sara;Gupta,PrateekK;Kent,KCraig;Matsumura,Jon
• 通讯作者: Matsumura,Jon