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 在所有与医学、心理健康和物质相关的障碍中，严重抑郁障碍(MDD)是 全球主要致病原因疾病负担；MDD是接受者痛苦和残疾的主要原因 退伍军人健康管理局(VHA)对他们的照顾。目前的治疗方法疗效有限，因为 只有大约30%的患者通过第一次抗抑郁药物治疗获得缓解。根据监管惯例， 术语难治性抑郁(TRD)用于抑郁症患者对两个或两个或更多的 在本期节目中进行更充分的治疗试验。如此定义，患有TRD的患者占 治疗资源的比例过大，尽管做出了这样的努力，但仍处于最高风险 患有慢性病，发展成复杂的药物滥用障碍和/或自杀身亡。CSP 576， VA增强和转换治疗改善抑郁结局(VAST-D)显示 与改用阿立哌唑相比，阿立哌唑缓解的可能性要大得多。 安非他酮。VAST-D的二次分析表明，阿立哌唑在 在长达六个月的治疗中，12周的汇款持续存在，无论患者是否 有共同发生的创伤后应激障碍。2019年，美国食品和药物管理局(FDA)审查了鼻腔内注射埃斯氯胺酮 作为治疗TRD的一种新疗法。埃斯氯胺酮的安全性和有效性在一系列 第三阶段研究，最终导致FDA批准埃斯氯胺酮(Spravato)用于治疗#年的TRD 成年人。拟议的研究将是一项开放标签、平行分组、随机的临床试验，最长可达6个月。 鼻内辅助性埃斯氯胺酮与阿立哌唑治疗退伍军人呼吸窘迫综合征的比较。这项研究将 评估鼻腔内辅助性埃斯氯胺酮的有效性、安全性和可接受性 阿立哌唑辅助治疗三叉神经痛。主要的假设是参与者接受了附加语 鼻腔注射埃斯氯胺酮在治疗6周后明显更有可能缓解，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评估 不知道治疗分配的独立评估者使用抑郁症快速清单 症状学临床医生评分(QDS-C)，这是一个经过充分验证的工具，通常很容易翻译 在其他抑郁症清单量表上。这项研究的目的是能够检测出 6周时缓解率达10%或以上。感兴趣的次要结果包括症状减轻 在6个月的随机治疗中，副作用和其他耐受性指数、自杀率和 生活质量和成本效益。