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”）中测试每日硝酸甘油降低骨折风险的有效性和安全性。本试验的主要目的是检验以下假设：与阿仑膦酸钠70 mg每周一次相比，每日一次硝酸盐可降低非椎骨骨折高危女性的非椎骨骨折风险。次要目的是检验以下假设：与阿仑膦酸钠相比，每日给予硝酸盐：（a）在降低椎骨骨折风险方面不劣于阿仑膦酸钠;（B）降低临床骨折风险;（c）在股骨颈和腰椎处产生更大的骨矿物质密度（BMD）增加。最后，我们将比较硝酸甘油和阿仑膦酸钠之间的不良事件的风险。 计划阶段的目标是为无骨折试验制定一项NIH提案。计划阶段的具体目标是：（1）确定硝酸盐治疗的配方和剂量;（2）最终确定样本量和入组标准，并计划招募策略;（3）确定和 聘请能够按时招募足够受试者的临床研究中心;（4）完成研究方案、操作手册、数据收集表和数据管理计划;（5）制定安全性和数据监测计划以及数据安全性监测委员会;（6）获得试验所需的监管批准;（7）制定研究预算和策略，以最大限度地降低试验成本;以及（8）编写并提交无骨折试验的建议书。 该计划阶段将为无骨折试验提供合理的设计、有效和可行的计划和建议。我们希望NO Fracture试验能够证明每日使用硝酸盐比阿仑膦酸钠更安全地降低非椎骨骨折的风险。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的使用，与目前的治疗方法相比，骨折的个人和社会负担将得到更大的减少。

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.