VA Aripiprazole vs. Esketamine for Treatment of Depression VAST-D II

VA 阿立哌唑与艾氯胺酮治疗抑郁症 VAST-D II

• 批准号: 10426080
• 负责人: SOMAIA MOHAMED
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426080
• 关键词: Acute; Adherence; Adult; Adverse effects; Algorithms; Antidepressive Agents; Benefits and Risks; Blinded; Bupropion; Caring; Chronic; Chronically Ill; Data; Decision Making; Depressed mood; Disease; Disease remission; Dissociation; Dose; Drug Costs; Effectiveness; Equipment and supply inventories; Feeling suicidal; Goals; Health; Hour; Intention; Knowledge; Major Depressive Disorder; Measures; Medical; Mental Depression; Mental Health; Mental Health Services; Mental disorders; Metabolic; Methodology; Monitor; Multicenter Studies; Neurocognitive; Oral; Outcome; Participant; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Post-Traumatic Stress Disorders; Practice Guidelines; Protocols documentation; Public Health; Quality of life; Randomized; Randomized, Controlled Trials; Research; Resources; Risk; Role; Safety; Sedation procedure; Series; Severities; Site; Substance abuse problem; Substance-Related Disorders; Suicide; Testing; Time; Translating; United States Food and Drug Administration; Veterans; Veterans Health Administration; active comparator; addiction; aripiprazole; atypical antipsychotic; burden of illness; clinical implementation; comparative; comparative effectiveness; cooperative study; cost; cost effective treatment; cost effectiveness; depressed patient; depressive symptoms; disability; discontinuation study; efficacy evaluation; follow-up; health care settings; high risk; improved; indexing; interest; inventory of depressive symptomatology; meetings; novel therapeutics; open label; participant enrollment; phase 3 study; pragmatic trial; primary outcome; programs; randomized, clinical trials; reduce symptoms; relapse prevention; risk mitigation; secondary analysis; secondary outcome; side effect; suicidal; suicidal behavior; suicidal risk; symposium; tool; treatment comparison; treatment strategy; treatment trial; treatment-resistant depression; trial comparing

Project Summary/Abstract Among all medical, mental health and substance related disorders, Major Depressive Disorder (MDD) is the leading cause disease burden worldwide; MDD is a major cause of suffering and disability for those receiving their care from the Veterans Health Administration (VHA). Current treatments have limited effectiveness as only about 30% of patients achieve remission with the first antidepressant treatment. By regulatory convention, the term treatment-resistant depression (TRD) is used when a depressed patient has not responded to two or more adequate treatment trials in the current episode. So defined, patients with TRD account for a disproportionately large share of treatment resources and, despite such efforts, are at the highest risk to become chronically ill, develop a complicating substance abuse disorder and/or die by suicide. The CSP 576, VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D), showed that adjunctive aripiprazole resulted in a significantly greater likelihood of remission as compared to switching to bupropion. Secondary analyses of VAST-D demonstrated that the advantage of adjunctive aripiprazole among 12-week remitters was sustained across up to six months of therapy and was evident whether or not patients had co-occurring PTSD. In 2019 the U.S. Food and Drug Administration (FDA) reviewed intranasal esketamine as a new therapy for treatment of TRD. The safety and efficacy of esketamine was evaluated in a series of phase III studies that ultimately led to the FDA approval of esketamine (Spravato) for the treatment of TRD in adults. The proposed study will be an open-label, parallel-group, randomized clinical trial of up to 6 months treatment of adjunctive intranasal esketamine vs. adjunctive aripiprazole in Veterans with TRD. This study will assess the efficacy, safety, and acceptability of adjunctive intranasal esketamine in direct comparison to adjunctive aripiprazole for therapy of TRD. The primary hypothesis is that participants receiving adjunctive intranasal esketamine will be significantly more likely to achieve remission after six weeks of treatment as compared to those who receive adjunctive aripiprazole. Depressive symptoms will be assessed by independent evaluators without knowledge of treatment assignment using the Quick Inventory of Depressive Symptomatology clinician rating (QIDS-C), which is a well-validated tool that commonly and is easily translated across other depression inventory scales. The study is powered to be able to detect an absolute difference in remission rates of 10% or larger at 6 weeks. Secondary outcomes of interest include symptom reduction across 6 months of randomized therapy, side effects and other tolerability indices, suicidality, and measures of quality of life and cost-effectiveness.

项目概要/摘要 在所有医学、心理健康和物质相关疾病中，重度抑郁症 (MDD) 是最严重的疾病。 全球主要疾病负担； MDD 是那些接受治疗的人遭受痛苦和残疾的主要原因 他们由退伍军人健康管理局 (VHA) 提供护理。目前的治疗方法效果有限 只有约 30% 的患者通过首次抗抑郁治疗获得缓解。根据监管惯例， 当抑郁症患者对两种或两种药物没有反应时，使用“难治性抑郁症”（TRD）一词。 当前事件中进行了更充分的治疗试验。按照这样的定义，TRD 患者占 治疗资源所占比例过高，尽管做出了这些努力，但仍面临着最高的风险 患有慢性病、出现复杂的药物滥用障碍和/或自杀身亡。 CSP 576， VA 增强和转换治疗以改善抑郁结果 (VAST-D) 表明 与改用阿立哌唑辅助治疗相比，阿立哌唑辅助治疗的缓解可能性显着增加 安非他酮。 VAST-D 的二次分析表明，阿立哌唑辅助治疗的优势 12 周缓解在长达 6 个月的治疗中持续存在，无论患者是否 患有同时发生的创伤后应激障碍（PTSD）。 2019年美国食品药品监督管理局（FDA）审查鼻内艾氯胺酮 作为治疗 TRD 的新疗法。艾氯胺酮的安全性和有效性经过一系列评估 III 期研究最终导致 FDA 批准 esketamine (Spravato) 用于治疗 TRD 成年人。拟议的研究将是一项为期长达 6 个月的开放标签、平行组、随机临床试验 辅助鼻内艾氯胺酮与辅助阿立哌唑治疗 TRD 退伍军人的比较。这项研究将 直接比较评估辅助鼻内艾氯胺酮的有效性、安全性和可接受性 阿立哌唑辅助治疗 TRD。主要假设是参与者接受辅助治疗 治疗六周后，鼻内艾氯胺酮将更有可能实现缓解，因为 与接受阿立哌唑辅助治疗的患者相比。抑郁症状将通过以下方式进行评估 独立评估者在不了解治疗分配的情况下使用抑郁症快速清单 症状学临床医生评级 (QIDS-C)，这是一种经过充分验证的工具，通常且易于翻译 跨越其他萧条库存规模。该研究旨在能够检测到的绝对差异 6 周时缓解率达到 10% 或更高。感兴趣的次要结果包括症状减轻 6 个月的随机治疗、副作用和其他耐受性指数、自杀倾向以及 生活质量和成本效益。