Feasibility of the Von Willebrand Disease Minimize Trial

描述(由申请人提供)：拟议的U34临床规划拨款合作协议是针对计划公告RFA-HL-12-023而设计的，旨在确定进行一项第三阶段随机对照临床试验(VWD最小化研究)的可行性，比较重组白介素11(rhIL-11)与目前推荐的非激素治疗氨甲环酸(TA)用于减少1型von Willebrand病(VWD)女性患者月经过多的可行性。在这笔规划拨款中，我们将确定进行第三阶段(R01)试验的可行性。这项研究的最初概念是由六名血友病治疗中心(HTC)医生作为四个临床试验概念之一开发的，他们是NHLBI科学状态(SOS)血友病/von Willebrand小组委员会的成员，他们是这项研究的指导委员会的成员。患有VWD的妇女的一个主要目标是减少月经过多和相关的发病率和生活质量差。目前的治疗方法受到毒性的限制，几乎没有随机试验来指导治疗。因此，更安全、更有效 我们需要药物。我们推测，每天皮下注射一次的rhIL-11在减少月经过多方面优于目前推荐的非激素类药物TA，每天三次，具有类似的毒性和可接受性，并改善生活质量。该项目的最终目标是确定并解决未来进行第二阶段随机对照临床试验的障碍，以减少VWD女性患者的月经过多。通过这种方法，我们希望准备、提炼和优化方法、形式和操作程序；并确定足够数量的参与地点和合格受试者，以确保进行第三阶段随机对照试验以减少VWD女性月经过多的可行性，其具体目标是：1.建立HTC基础设施，由50多名HTC医生组成，就试验设计、受试者招募和参与建立共识，以确保有足够数量的合格受试者进行未来R01 20周的临床随机试验，比较rhIL-11和TA在18-45岁1型VWD女性中减少月经出血的作用。HTC网络将通过1)对HTC医生和患有1型VWD的女性进行结构化访谈，以确定试验设计的可接受性和参与潜力；2)与指导委员会和U24临床资源合作，以优化试验设计、招募策略，并准备病例报告表格和操作手册；3)开发和试点基于网络的数据输入系统；4)与HTC附属妇科医生举行探索性会议，以确定参与试验和招募受试者的可能性；以及5)聘请一名专门的护士协调员，为HTC准备IRB提交和合同。目的2.确定一项为期20周的III期随机、优势、平行对照临床试验的可行性，比较皮下注射重组人IL-11和口服TA在减少HTC登记的18-45岁1型VWD女性月经过多方面的作用。为此，将通过1)为VWD妇女的护士培训准备一个关于皮下注射技术的教育模块；2)成立一个独立的评审委员会，对研究对象的主要疗效结果和其他措施进行集中审查和监测；3)制定安全停止指南，以确保干预的安全性，最大限度地减少液体滞留和低钾血症；4)通过基于网络的数据输入，建立与研究对象数据相关联的血液样本储存库；以及5)寻求社区咨询委员会的建议，以提供反馈和促进沟通，以确保未来的第三阶段试验成功。(摘要结束)

DESCRIPTION (provided by applicant): The proposed U34 Clinical Planning Grant Cooperative Agreement is designed in response to Program Announcement RFA-HL-12-023, to determine the feasibility of conducting a Phase III randomized controlled clinical trial, The VWD Minimize Study, comparing recombinant interleukin-11 (rhIL-11) with tranexamic acid (TA), the current recommended non-hormonal treatment, to reduce menorrhagia in women with type 1 von Willebrand disease (VWD). In this planning grant, we will establish the feasibility of conducting a Phase III (R01) trial. The original concept for this study was developed as one of four clinical trial concepts by six hemophilia treatment center (HTC) physicians, members of the NHLBI State of the Science (SoS) Hemophilia/von Willebrand Subcommittee, who are members of the Steering Committee for this study. A major goal for women with VWD is to reduce menorrhagia and associated morbidity and poor quality of life. Current treatments are limited by toxicities, and few randomized trials are available to guide treatment. Thus, safer, more effective drugs are needed. We hypothesize that rhIL-11, given by subcutaneous injection once daily, is superior to the current recommended non-hormonal agent, TA, given orally three times daily, in reducing menorrhagia, with similar toxicity and acceptability, and improved quality of life. The ultimate goal of this project is to identify and resolve barriers to the conduct of a future phase II randomized, controlled clinical trial to reduce menorrhagia in women with VWD. By this approach, we hope to prepare, refine, and optimize methods, forms, and operating procedures; and determine a sufficient number of participating sites and eligible subjects to assure the feasibility of conducting a Phase III randomized controlled trial to reduce menorrhagia in women with VWD, the specific aims of which are: Aim 1. To establish an HTC infrastructure of 50+ HTC physicians to build consensus on trial design, subject recruitment and participation to assure a sufficient number of eligible subjects to conduct a future R01 20-week clinical randomized trial to compare rhIL-11 and TA to reduce menstrual bleeding in females 18-45 years with type 1 VWD. The HTC network will be operationalized by 1) conducting structured interviews with HTC physicians and women with type 1 VWD to determine acceptability of trial design and participation potential; 2) collaborating with a Steering Committee and the U24 Clinical resource to optimize trial design, recruitment strategy, and prepare case report forms and a manual of operations; 3) developing and pilot testing a web-based data entry system; 4) conducting exploratory meetings with HTC-affiliated gynecologists to determine potential for trial participation and subject recruitment; and 5) hiring a dedicated nurse coordinator to prepare IRB submission and contracts for HTCs. Aim 2. To determine the feasibility of a phase III 20-week randomized, superiority, parallel arm clinical trial to compare subcutaneous rhIL-11 with oral TA in reducing menorrhagia in females 18-45 years old with type 1 VWD enrolled at HTC. This will be accomplished by 1) preparing an education module on subcutaneous injection technique for nurse training of women with VWD; 2) setting up an independent adjudication committee for centralized review and monitoring of the primary efficacy outcome and other measures in study subjects; 3) establishing safety stopping guidelines to assure safety of the intervention, to minimize fluid retention and hypokalemia; 4) setting up a repository of blood samples linked to study subject data via web-based data entry; and 5) seeking advice of a community advisory board to provide feedback and promote communication to assure success of the future Phase III trial. (End of Abstract)