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.

项目总结/摘要 在所有的医学、心理健康和物质相关的疾病中，重度抑郁症（MDD）是最常见的疾病。 世界范围内的主要原因疾病负担; MDD是那些接受治疗的人遭受痛苦和残疾的主要原因 退伍军人健康管理局（VHA）的护理。目前的治疗效果有限， 只有约30%的患者在第一次抗抑郁治疗后达到缓解。按照管理惯例， 当抑郁症患者对两种或两种以上的抗抑郁药没有反应时，使用术语难治性抑郁症（TRD）。 更充分的治疗试验。如此定义，TRD患者占 尽管作出了这些努力，但仍面临最高的风险， 患上慢性病，发展为复杂的药物滥用障碍和/或自杀死亡。CSP 576， VA增强和转换治疗改善抑郁症的结果（VAST-D）显示， 阿立哌唑的连续治疗导致缓解的可能性显著高于转换为 安非他酮VAST-D的二次分析表明，阿立哌唑在 12-在长达6个月的治疗中， 同时患有创伤后应激障碍2019年，美国食品药品监督管理局（FDA）审查了鼻内艾司氯胺酮 作为治疗TRD的新疗法。在一系列研究中评价了艾司氯胺酮的安全性和疗效， 最终导致FDA批准艾司氯胺酮（Spravato）用于治疗TRD的III期研究， 成年人了拟议的研究将是一项为期6个月的开放标签、平行组、随机临床试验 TRD退伍军人中连续鼻内艾司氯胺酮与连续阿立哌唑的治疗。本研究将 评估连续性鼻内艾司氯胺酮的疗效、安全性和可接受性，与 阿立哌唑治疗TRD主要的假设是， 鼻内艾司氯胺酮治疗6周后达到缓解的可能性显著更大， 与服用阿立哌唑的人相比。抑郁症状将由以下人员评估 不了解治疗分配的独立评价者使用抑郁症快速量表 症状学临床医生评分（QIDS-C），这是一种经过充分验证的工具，通常且易于翻译 在其他抑郁量表上的表现该研究的效力在于能够检测以下方面的绝对差异： 6周时的缓解率为10%或更高。关注的次要结局包括症状减轻 在6个月的随机治疗中，副作用和其他耐受性指数、自杀倾向和 生活质量和成本效益。