Abdominal aortic aneurysms (AAA) are a common (2-3% of population affected) and lethal problem causing 15,000 deaths/year 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 (<5.5 cm) 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. In the absence of effective medical treatment, a costly alternative ($20,000/procedure), endograft repair, may become the treatment of choice 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. There is laboratory, animal model and observational evidence that doxycycline, working as an MMP inhibitor, can prevent progression of AAA, although the clinical evidence for this effect is preliminary. The public health impact of testing the safety and efficacy of doxycycline in the treatment of abdominal aortic aneurysms derives from the large number of patients (hundreds of thousands) who could avoid surgical or endograft therapy (costing in excess of $200,000,000 per year) or who could avoid being recommended an inefficacious therapy. 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. The purpose of this proposal is to develop a prospective, randomized trial to test the hypothesis that doxycycline will inhibit the growth of small AAA.
Our specific aims are to: 1) Establish the research team for the clinical trial (specifying clinical sites, number and gender/race/ethnicity of patients available, central facility roles and sites); 2) Develop tools for data management and oversight of research (quality control/assurance procedures, safety monitoring plan, methods, hardware, software, and transmittal systems for data collection and plan for training study personnel); 3) Define our recruitment strategy (confirming eligibility criteria, plans for recruitment and retention); 4) Finalize the Protocol (experimental design, hypotheses, imaging procedures, other outcomes, image and data analysis, sample size); and 5) Develop the procedures manual including establishing the means to assure standardization of procedures (evaluations, randomizations, treatment, follow-up, statistical analysis, administration). These efforts will lead to submission of an investigator- initiated grant application to the National Institute on Aging (NIA) to test the role of doxycycline for this problem with large public health impact. The public health impact of testing the safety and efficacy of doxycycline in the treatment of abdominal aortic aneurysms derives from the large number of patients (hundreds of thousands) who could avoid surgical or endograft therapy (costing in excess of $200,000,000 per year) or who could avoid being recommended an inefficacious therapy. ? ? ? ? ? ?
|Baxter, B Timothy; Matsumura, Jon; Curci, John et al. (2016) Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT): Design of a Phase IIb, placebo-controlled, double-blind, randomized clinical trial of doxycycline for the reduction of growth of small abdominal aortic aneurysm. Contemp Clin Trials 48:91-8|
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|Baxter, B Timothy; Terrin, Michael C; Dalman, Ronald L (2008) Medical management of small abdominal aortic aneurysms. Circulation 117:1883-9|