Clinical Trial of High Dose CoQ10 in ALS-QALS-=STAT

描述(由申请人提供)：QALS-CLIN和QALS-STAT是两个独立但高度协调的单元，它们共同构成了QALS，这是一项辅酶Q10对照安慰剂的两阶段、II期、随机、双盲、多中心临床试验(目标招募18个临床站点的185名患者)。第一阶段确定两种剂量的辅酶Q10中的哪一种是首选的(1,000 mg。或2000毫克。每天)，使用选择程序将所需的患者数量控制在最低限度。第二阶段将首选剂量与安慰剂进行比较，以评估是否有足够的有效性证据来证明进入第三阶段试验的合理性。主要的结果衡量指标是肌萎缩侧索硬化症功能评定量表修订版(ALSFRsr)从基线(随机)到9个月的变化，初步研究已证实它是生存黄金标准的替代品。四个预先指定的第二支持假设也被检验。基于可能被证明更敏感的ALSFRsr亚分的替代结果衡量标准将在第三次分析中作为未来试验的候选者进行探索。 QALS-STAT的目标是：1)将随访时间和所需患者数量降至最低。2)管理、高效整合并负责所有QALS数据管理和统计业务。3)及时将QALS CLIN首席研究员履行职责所需的所有数据传输到临床协调中心(CCC)，以确保患者安全和指导所有临床操作。目标1是通过选择程序和使用代理终点来实现的，这将后续时间缩短了50%。目标2是由一个统计分析中心实现的，该中心的工作人员在协调、数据管理和临床试验编程以及他们的统计要求方面拥有丰富的经验。目标3由QALS-CLIN和QALS-STAT调查员和高级协调员组成的业务委员会确保，该委员会根据严格规定和受控的通信协议经常举行会议。

DESCRIPTION (provided by applicant): QALS-CLIN and QALS-STAT are two independent, but highly coordinated units, which together constitute QALS, a two-stage, phase II, randomized, placebo-controlled, double-blind, multi-center clinical trial of Coenzyme Q10 against placebo (target enrollment 185 patients at 18 clinical sites). The first stage identifies, which of two doses of CoQ10 is preferred (1,000 mg. or 2,000 mg. daily), using a selection procedure to hold the number of patients required to a minimum. The second stage compares the preferred dose against placebo to assess whether there is sufficient evidence of efficacy to justify proceeding to a phase III trial. The primary outcome measure is the change in Amyotrophic Lateral Sclerosis Functional Rating Scale revised (ALSFRSr) score from baseline (randomization) to 9 months, which preliminary research has validated as a surrogate for the gold standard of survival. Four pre-specified secondary supporting hypotheses are also tested. Alternative outcome measures, based on ALSFRSr subscores that may prove more sensitive, will be explored in tertiary analyses as candidates for future trials. The goals of QALS-STAT are: 1) To minimize follow-up-time and number of patients required. 2) To conduct, efficiently integrate, and be responsible for all QALS data management and statistical operations. 3) To transmit to the Clinical Coordinating Center (CCC) in a timely fashion all of the data which the principal investigator of QALS CLIN needs to meet her responsibilities, in terms of ensuring patient safety and directing all clinical operations. Goal 1 is accomplished by the selection procedure, and the use of a surrogate endpoint, which cuts follow-up time by 50%. Goal 2 is achieved by a Statistical Analysis Center, whose personnel have extensive experience in coordination, data management, and programming for clinical trials, as well as their statistical requirements. Goal 3 is ensured by an Operations Committee of QALS-CLIN and QALS-STAT investigators and senior coordinators, which meets frequently under tightly specified and controlled communication protocols.