CLINICAL TRIAL: DEXAMETHASONE-SPARING STUDY COMPARING (HERF) TO PLACEBO

临床试验：地塞米松节约研究 (HERF) 与安慰剂的比较

• 批准号: 7717882
• 负责人: Lawrence D Recht
• 金额: $ 0.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717882
• 关键词: Adverse effects; Blinded; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Daily; Data Element; Deterioration; Dexamethasone; Dose; Double-Blind Method; Drops; End Point; Failure; Funding; Grant; Institution; Karnofsky Performance Status; Label; Measures; Medical; Monitor; Myopathy; Neoplasm Metastasis; Nervous System Physiology; Neurologic Examination; Patients; Performance; Pharmaceutical Preparations; Placebo Control; Placebos; Quality of life; Randomized; Relative (related person); Research; Research Personnel; Resources; Safety; Score; Signal Transduction; Source; Steroids; Symptoms; Time; United States National Institutes of Health; Visit; Week; day; follow-up

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Two hundred patients, randomized to one of two treatment groups, will participate in this double blind, placebo-controlled, 12-week study. Patient randomization will be stratified by (1) primary or metastatic tumor, (2) open-label dexamethasone dose at Baseline (4-<8 mg/day, 8-16 mg/day or 17-24 mg/day) and (3) Karnofsky Performance Scale (50-70 or 80-100). Attempts will be made to reduce daily dexamethasone dose by 50% during the first two weeks of the 12-week study. The 50% reduction is to be maintained until Week 5, after which further reductions may be attempted at the discretion of the Investigator. The primary endpoint is the proportion of patients in each treatment group who are Responders at Week 2 and who continue to be Responders at Week 5. Responders are defined as study patients who demonstrate the following: (a) 50% or greater reduction in dexamethasone dose relative to Baseline; (b) overall 10-Item Neurological Examination Score unchanged or lower compared to Baseline (c) Karnofsky Performance Score unchanged or increased compared to Baseline. All patients not fulfilling the definition of Responder for any reason, including missing data elements, patient drop out, or failure to achieve a 50% reduction in dexamethasone without deterioration in neurological function as measured by the 10- Item Neurological Examination Score and the Karnofsky Performance Score will be scored as non-responders. Further dexamethasone reductions after Week 5, overall safety and steroid associated side effects will be evaluated over the course of the trial. Secondary efficacy endpoints include the following: percent of patients in each treatment group achieving 50% reduction in dexamethasone usage relative to Baseline by Week 2 without deterioration in neurological function; the proportion of patients in each treatment group who are Responders at Week 2 and who continue to be Responders at Weeks 5 and 8. In addition, change from Baseline will be examined for the signal symptom, FACT-Br quality of life module results; myopathy assessment results. From Baseline through Week 5 of study treatment, it is mandatory that the Neurological Examinations be conducted by the same examiner. All efforts will be made to assure that the same investigator perform the Neurological Examinations after Week 5. A Follow-up visit will occur at Week 16. For patients who do not reach a 50% dexamethasone dose reduction by Week 2, continued tapering attempts must be discussed with the Medical Monitor. Patients who discontinue blinded study drug early will be seen for an Early Study Drug Discontinuation visit at time of discontinuation. All patients will have a final Follow-up visit at Week 16. For patients who discontinue study drug prior to Week 10, an additional Unscheduled Follow-up will occur 4 weeks after early study drug discontinuation.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 200 名患者被随机分配到两个治疗组之一，将参加这项为期 12 周的双盲、安慰剂对照研究。患者随机分组将按以下因素进行分层：(1) 原发性或转移性肿瘤，(2) 基线时的开放标签地塞米松剂量（4-<8 毫克/天、8-16 毫克/天或 17-24 毫克/天）和 (3) 卡诺夫斯基体能量表（50-70 或 80-100）。 在为期 12 周的研究的前两周，将尝试将每日地塞米松剂量减少 50%。 50% 的减少将维持到第 5 周，之后研究者可酌情尝试进一步减少。主要终点是每个治疗组中第 2 周有反应者和第 5 周继续有反应者的患者比例。反应者定义为表现出以下情况的研究患者： (a) 地塞米松剂量相对于基线减少 50% 或更多； (b) 总体 10 项神经系统检查得分与基线相比保持不变或更低 (c) 卡诺夫斯基表现得分与基线相比保持不变或增加。所有因任何原因（包括缺失数据元素、患者退出或未能在不恶化神经功能（通过 10 项神经学检查评分和卡诺夫斯基表现评分衡量）的情况下实现地塞米松减少 50% 的患者）不符合响应者定义的患者将被评分为无响应者。第 5 周后进一步减少地塞米松、总体安全性和类固醇相关副作用将在试验过程中进行评估。次要疗效终点包括以下内容：到第 2 周，每个治疗组中地塞米松使用量相对于基线减少 50% 且神经功能未恶化的患者百分比；每个治疗组中第 2 周有反应者以及第 5 周和第 8 周继续有反应者的患者比例。此外，将检查信号症状、FACT-Br 生活质量模块结果相对于基线的变化；肌病评估结果。 从基线到研究治疗的第 5 周，神经系统检查必须由同一位检查员进行。将尽一切努力确保由同一位研究者在第 5 周后进行神经学检查。随访将在第 16 周进行。 对于在第 2 周未达到地塞米松剂量减少 50% 的患者，必须与医疗监察员讨论继续逐渐减量的尝试。提前停止盲法研究药物的患者将在停药时接受早期研究药物停药访视。所有患者都将在第 16 周进行最后一次随访。对于在第 10 周之前停止研究药物的患者，将在早期停止研究药物后 4 周进行一次额外的计划外随访。