The TAKEOFF Trial: Clinical Trial Planning Grant

TAKEOFF 试验：临床试验计划补助金

• 批准号: 8031114
• 负责人: JEFFREY R. CURTIS
• 金额: $ 14.65万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-08-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8031114
• 关键词: Anti-Tumor Necrosis Factor Therapy; Antirheumatic Agents; Arthritis; Biochemistry; Biological Markers; Biological Response Modifier Therapy; British; Clinic; Clinical; Clinical Trials; Combined Modality Therapy; Data; Data Analyses; Data Collection; Development; Disease; Disease remission; Disease-Modifying Second-Line Drugs; Dose; Drug Kinetics; Early treatment; Etanercept; Flare; Grant; Health; Hydroxychloroquine; Individual; Infection; Injection of therapeutic agent; Internal Medicine; Methotrexate; Outcome Measure; Patients; Pharmaceutical Economics; Pharmaceutical Preparations; Positioning Attribute; Prevalence; Process; Randomized; Research; Research Design; Rheumatoid Arthritis; Safety; Sales; Site; Source; Sulfasalazine; TNF gene; Testing; Therapeutic; Toxic effect; United States National Institutes of Health; Variant; adalimumab; arthritis therapy; cancer risk; clinical efficacy; clinical remission; cohort; cost; data management; disorder control; dosage; evidence base; follow-up; improved; indexing; infliximab; news; patient safety; response; rheumatologist

DESCRIPTION (provided by applicant): Anti-TNF drugs (adalimumab, certolizumab, etanercept, golimumab, infliximab) are commonly used with methotrexate (MTX) in rheumatoid arthritis (RA). Despite the development of these new and exciting biological therapies for the treatment of RA, their relatively high costs (< $24,000/year) and possible toxicities (infection, cancer risk, injection site problems) are drawbacks to their use. MTX remains an anchor drug for RA therapy; however, there is substantial unexplained variation in patient response to MTX therapy. It is unknown if anti- TNF drugs may ultimately be discontinued in individuals on dual therapy. The ability to taper an anti-TNF drug may depend on the ability to optimize MTX therapy or the addition of an additional disease modifying antirheumatic drugs (DMARD). We propose a clinical trial planning grant to convene an expert panel to refine the study design, outcome measures, data collection and data analysis for the TAKEOFF Trial (Optimizing Methotrexate and Discontinuing Anti-TNF Agents in RA). This study will test the hypothesis that among patients who have been in clinical remission (CDAI d 2.8) for at least 6 months, patients randomized to discontinue or reduce the dose of anti-TNF therapy with either concomitant optimization of MTX or addition of SSZ + HCQ will have a likelihood of continued remission that is non-inferior compared to patients randomized to continue anti-TNF therapy + MTX. The clinical trial planning process will involve experts related to RA trials planning, MTX biochemistry, outcome measures and data analysis. It is expected at the end of the planning process that an NIH grant will be submitted related to optimization discontinuing biological therapies.

描述（由申请人提供）：抗TNF药物（Adalimumab，Certolizumab，etanercept，Golimumab，英夫利昔单抗）在类风湿关节炎（RA）中常用于甲氨蝶呤（MTX）。尽管开发了这些新的令人兴奋的生物学疗法用于治疗RA，但它们的成本相对较高（每年24,000美元）和可能的毒性（感染，癌症风险，注射现场问题）是其使用的弊端。 MTX仍然是一种用于RA治疗的锚固药。但是，患者对MTX治疗的反应有很大的无法解释的差异。尚不清楚双重疗法的个体中是否可能停止抗TNF药物。逐渐变细的抗TNF药物的能力可能取决于优化MTX治疗的能力或增加了修饰抗疾病药物（DMARD）的其他疾病。我们提出了一项临床试验计划赠款，以召集专家小组，以完善起飞试验的研究设计，结果指标，数据收集和数据分析（优化RA中的甲氨蝶呤和停用抗TNF代理）。这项研究将检验以下假设：在临床缓解（CDAI D 2.8）至少6个月的患者中，患者随机停止或减少抗TNF治疗的剂量并伴随MTX优化MTX或添加SSZ + HCQ的这一患者将与持续缓解相比，与患者的持续缓解相比，与患者进行了较为替代 + MORSATS + MORTID FTHF anti-TNF相比，临床试验计划过程将涉及与RA试验计划，MTX生物化学，结果测量和数据分析有关的专家。预计在计划过程的结束时，将提交与优化的终止生物疗法有关的NIH赠款。