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.

项目摘要/摘要 在所有医学，心理健康和物质与与物质有关的疾病中，重度抑郁症（MDD）是 全世界领先的疾病负担； MDD是接受者的主要原因和残疾 他们从退伍军人卫生管理局（VHA）的护理。当前治疗的有效性有限 只有大约30％的患者通过第一种抗抑郁药治疗来缓解。按照监管惯例 当抑郁症患者未对两个或 在当前发作中进行了更足够的治疗试验。如此定义，有TRD的患者占 不成比例的治疗资源份额不成比例，尽管做出了努力，但仍有最高的风险 长期生病，发展出复杂的药物滥用障碍和/或自杀死亡。 CSP 576， VA增强和改善抑郁症结果的治疗方法（vast-D）表明 与切换相比 安非他酮。大量D的次要分析表明，辅助阿立哌唑之间的优势 在长达六个月的治疗中，12周的汇款持续了 具有同时发生的PTSD。 2019年，美国食品药品监督管理局（FDA）审查了鼻内埃斯酮胺 作为TRD治疗的新疗法。在一系列 第三阶段的研究最终导致了FDA批准Esketamine（Spravato）用于治疗TRD 成年人。拟议的研究将是一项开放标签，平行组，随机临床试验，最多6个月 辅助性鼻腔内甲胺与TRD退伍军人中的辅助阿立哌唑的处理。这项研究会 评估辅助性鼻腔内孔胺胺的功效，安全性和可接受性，直接比较 用于治疗TRD的辅助阿立哌唑。主要假设是参与者接受辅助 六周后，鼻腔内卵胺胺在治疗六周后的可能性更大 与接受辅助阿立哌唑的人相比。抑郁症状将由 独立的评估者，不知道使用抑郁症的快速库存治疗分配 症状学临床医生评级（QIDS-C），它是一种经过验证的工具，通常很容易翻译 在其他抑郁量表量表中。该研究有能力检测 6周时的缓解率为10％或更高。感兴趣的次要结果包括减轻症状 在6个月的随机治疗，副作用和其他耐受性指数，自杀性和措施 生活质量和成本效益。