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: 8722021
• 负责人: MARGARET VICTORIA RAGNI
• 金额: $ 21.3万
• 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/8722021
• 关键词: Applications Grants; Blood specimen; Case Report Form; Clinical; Clinical Trials; Clinical Trials Design; Commit; Communication; Communities; Consensus; Contracts; Data; Enrollment; Feedback; Female; Future; Goals; Grant; Guidelines; Gynecologist; Hemophilia A; Hemorrhage; Hypokalemia; Institutional Review Boards; Intervention; Interview; Learning Module; 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临床规划资助合作协议是根据项目公告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，以减少1型血管性血友病（VWD）妇女的月经过多。在此计划拨款中，我们将确定进行III期（R01）试验的可行性。这项研究的最初概念是由六位血友病治疗中心（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，他们是这项研究指导委员会的成员。妇女的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以指导治疗。因此，更安全，更有效