Feasibility of the Von Willebrand Disease Minimize Trial

冯维勒布兰德病最小化试验的可行性

• 批准号: 8566255
• 负责人: MARGARET VICTORIA RAGNI
• 金额: $ 21.55万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8566255
• 关键词: Applications Grants; Blood specimen; Case Report Form; Clinical; Clinical Trials; Clinical Trials Design; Commit; Communication; Communities; Consensus; Contracts; Data; Education; Enrollment; Feedback; Female; Future; Goals; Grant; Guidelines; Gynecologist; Hemophilia A; Hemorrhage; Hypokalemia; Institutional Review Boards; Intervention; Interview; Link; Liquid substance; Manuals; Measures; Menorrhagia; Menstrual cycle; Methods; Monitor; Morbidity - disease rate; NIH Program Announcements; National Heart, Lung, and Blood Institute; Nurses; Online Systems; Oprelvekin; Oral; Outcome; Patients; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Physicians; Procedures; Protocols documentation; Quality of life; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recruitment Activity; Research Infrastructure; Resources; Safety; Science; Site; Structure; Study Subject; Subcutaneous Injections; System; Testing; Time; Toxic effect; Training; Tranexamic Acid; U-Series Cooperative Agreements; Woman; Women Physicians; Work; abstracting; adjudication; arm; design; improved; meetings; member; nursing technique; operation; randomized trial; repository; response; subcutaneous; success; treatment center; von Willebrand Disease

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)

描述（由申请人提供）：拟议的 U34 临床规划拨款合作协议是根据计划公告 RFA-HL-12-023 设计的，旨在确定进行 III 期随机对照临床试验（VWD 最小化研究）的可行性，该试验将重组白细胞介素 11 (rhIL-11) 与目前推荐的非激素治疗氨甲环酸 (TA) 进行比较，以减少 患有 1 型血管性血友病 (VWD) 的女性月经过多。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。本研究的最初概念是由六名血友病治疗中心 (HTC) 医生提出的四个临床试验概念之一，他们是 NHLBI 科学状况 (SoS) 血友病/冯维勒布兰德小组委员会的成员，也是本研究指导委员会的成员。患有 VWD 的女性的一个主要目标是减少月经过多以及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，并且很少有随机试验可以指导治疗。因此，更安全、更有效 需要药物。我们假设每天一次皮下注射的rhIL-11在减少月经过多方面优于目前推荐的非激素药物TA（每天口服3次），具有相似的毒性和可接受性，并改善了生活质量。 该项目的最终目标是确定并解决未来进行 II 期随机对照临床试验的障碍，以减少 VWD 女性的月经过多。通过这种方式，我们希望准备、细化、优化方法、形式、操作流程；并确定足够数量的参与地点和合格受试者，以确保开展 III 期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： 目标 1. 建立由 50 多名 HTC 医生组成的 HTC 基础设施，就试验设计、受试者招募和参与达成共识，以确保有足够数量的合格受试者进行未来的 R01 为期 20 周的临床随机试验，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，优化试验设计、招募策略，并准备病例报告表和操作手册； 3）开发并试点测试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，以确定参与试验和受试者招募的潜力； 5) 聘请一名专门的护士协调员来准备 IRB 提交文件和 HTC 合同。目标 2. 确定一项为期 20 周的 III 期随机、优效、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可行性。这将通过以下方式实现： 1) 准备皮下注射技术教育模块，用于对患有 VWD 的妇女进行护士培训； 2）设立独立的评审委员会，对研究对象的主要疗效结局和其他措施进行集中审查和监测； 3) 建立安全停止指南以确保干预的安全性，尽量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对象数据链接的血液样本存储库； 5) 寻求社区咨询委员会的建议，提供反馈并促进沟通，以确保未来 III 期试验的成功。 （摘要完）