The NO Fracture Planning Grant

描述(由申请人提供)：我们建议在一年的随机试验(一氧化氮骨折试验，又名‘无骨折试验’)中测试每日服用硝酸甘油降低骨折风险的有效性和安全性。我们试验的主要目的是验证这样一种假设，即与每周一次的阿伦磷酸钠70毫克相比，代硝酸盐可降低此类骨折高危女性的非脊椎骨折风险。第二个目的是验证这样的假设：与阿伦磷酸钠相比，每天服用硝酸盐：(A)在降低脊椎骨折风险方面不逊于阿伦磷酸钠；(B)降低临床骨折风险；(C)在股骨颈和腰椎产生更大的骨密度(BMD)增加。最后，我们将比较硝酸甘油和阿伦磷酸钠不良事件的风险。规划阶段的目标是制定一项NIH建议，为无骨折试验提供资金。规划阶段的具体目标是：(1)决定硝酸盐治疗的配方和剂量；(2)最后确定样本数量和招生标准，并计划招募战略；(3)确定和 (4)完成研究方案、操作手册、数据收集表格和数据管理计划；(5)制定安全和数据监测计划以及数据安全监测委员会；(6)为试验获得必要的监管批准；(7)制定研究预算和战略，以将试验成本降至最低；以及(8)撰写并提交无骨折试验的提案。这一规划阶段将为无骨折试验带来合理的设计、高效可行的计划和建议。我们期望无骨折试验能证明每日硝酸盐的使用比阿伦磷酸钠更安全地降低非椎体骨折的风险。如果成功，这项试验的结果将导致这种廉价药物在世界范围内使用，比目前的治疗方法更能减轻骨折的个人和社会负担。

DESCRIPTION (provided by applicant): We propose to test the efficacy and safety of daily nitroglycerin for reduction in risk of fractures in a year randomized trial (Nitric Oxide Fracture Trial - aka 'NO Fracture Trial'). Our primary aim for the trial is to test the hypothesis that dail nitrates, compared with alendronate 70 mg once weekly reduces the risk of nonvertebral fracture in women at high risk for such fractures. The secondary aims are to test the hypotheses that, compared with alendronate, daily nitrate administration: (a) Is not inferior to alendronate fr reduction in risk of vertebral fracture; (b) reduces the risk of clinical fractures; and (c) producs greater increases in bone mineral density (BMD) at femoral neck and lumbar spine. Lastly, we will compare the risk of adverse events between nitroglycerin and alendronate. The goal in the planning phase is to develop an NIH proposal for funding for the NO Fracture Trial. The specific aims for the planning phase are: (1) decide the formulation and dose of the nitrate treatment; (2) finalize the sample size and enrollment criteria, and plan recruitment strategies; (3) identify and engage clinical sites capable of on-time recruitment of enough participants; (4) complete the study protocol, operations manuals, data collection forms and plans for data management; (5) develop the plan for safety and data monitoring and a data safety monitoring board; (6) obtain the necessary regulatory approvals for the trial; (7) develop the study budget and strategies to minimize the cost of the trial; and (8) write and submit the proposal for the NO Fracture Trial. This planning phase will lead to a well-reasoned design, efficient and feasible plan and proposal for the NO Fracture trial. We expect the NO Fracture Trial to demonstrate that the use of daily nitrate safely reduces the risk of nonvertebral fractures more than alendronate. If successful, findings from this trial would lead to world-wide use of this inexpensive medicine with greater reduction in the personal and social burden of fractures than achievable with current therapy.