Feasibility of the Von Willebrand Disease Minimize Trial

描述（申请人提供）：拟定的U34临床计划资助合作协议旨在响应项目公告RFA-HL-12-023，以确定进行III期随机对照临床试验的可行性，VWD最小化研究，比较重组白细胞介素-11（rhIL-11）与氨甲环酸（TA），目前推荐的非激素治疗，减少1型血管性血友病（VWD）女性的月经过多。在这项规划补助金中，我们会确定进行第III期（R 01）试验计划的可行性。本研究的原始概念是由六名血友病治疗中心（HTC）医生开发的四个临床试验概念之一，他们是NHLBI科学状态（SoS）血友病/von Willebrand小组委员会的成员，也是本研究指导委员会的成员。VWD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。目前的治疗受到毒性的限制，并且很少有随机试验可用于指导治疗。因此，更安全，更有效 需要药物。我们假设，rhIL-11，皮下注射给药，每日一次，上级目前推荐的非激素类药物，TA，口服给药，每日三次，在减少月经过多，具有相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和解决未来II期随机对照临床试验的障碍，以减少VWD女性的月经过多。通过这种方法，我们希望准备，完善和优化方法，形式和操作程序;并确定足够数量的参与中心和合格受试者，以确保进行III期随机对照试验的可行性，以减少VWD女性的月经过多，其具体目标是：目标1。建立由50多名HTC医生组成的HTC基础设施，以就试验设计、受试者招募和参与达成共识，确保有足够数量的合格受试者进行未来R 01 20周临床随机试验，以比较rhIL-11和TA减少18-45岁1型VWD女性月经出血的效果。HTC网络将通过以下方式运作：1）对HTC医生和1型VWD女性患者进行结构化访谈，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，并准备病例报告表和操作手册; 3）开发和试点测试基于网络的数据输入系统; 4）与HTC附属妇科医生进行探索性会议，以确定参与试验和受试者招募的可能性; 5）聘请专门的护士协调员为HTC准备IRB提交文件和合同。目标2.确定一项III期20周随机、优效性、平行组临床试验的可行性，以比较皮下注射rhIL-11与口服TA在减少HTC入组的18-45岁1型VWD女性月经过多方面的作用。这将通过以下方式实现：1）编写皮下注射技术教育模块，用于VWD女性护士培训; 2）成立独立裁定委员会，集中审查和监测研究受试者的主要疗效结局和其他指标; 3）制定安全性停药指南，以确保干预的安全性，最大限度地减少液体潴留和低钾血症; 4）通过基于网络的数据输入建立与研究受试者数据相关联的血液样本库;以及5）寻求社区咨询委员会的建议，以提供反馈并促进沟通，以确保未来III期试验的成功。(End摘要）

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)