The MIND USA Study

美国 MIND 研究

• 批准号: 8042197
• 负责人: E Wesley ELY
• 金额: $ 151.91万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-15 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8042197
• 关键词: APACHE II; Accounting; Acute; Address; Adopted; Adult; Affect; Age; Aging; American; Antipsychotic Agents; Arrhythmia; Brain; Cardiac; Caring; Cessation of life; Clinical; Clinical Pharmacology; Cognitive; Coma; Comorbidity; Confusion; Consent; Critical Care; Critical Illness; Death Rate; Delirium; Dementia; Development; Discipline; Discipline of Nursing; Disease; Double-Blind Method; Elderly; Enrollment; Ensure; Environmental air flow; Functional disorder; Future; Geriatric Psychiatry; Guidelines; Haloperidol; Hospitals; Hour; Impaired cognition; Incidence; Intensive Care; Intensive Care Units; Intravenous; Investigation; Length of Stay; Measures; Mechanical ventilation; Medical; Medicine; Monitor; Neuroleptic Malignant Syndrome; Neurologic Dysfunctions; Neurosciences; Older Population; Operative Surgical Procedures; Organ; Outcome; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Population; Post-Traumatic Stress Disorders; Quality of life; Randomized; Reporting; Risk Factors; Role; Safety; Sample Size; Sepsis; Severities; Severity of illness; Shapes; Shock; Subgroup; Surgical Intensive Care; Symptoms; Therapeutic; Toxic effect; United States; Vasoconstrictor Agents; Work; aging brain; atypical antipsychotic; brain research; clinical practice; cost; effective therapy; efficacy testing; follow-up; functional outcomes; high risk; human old age (65+); improved; modifiable risk; mortality; neuropsychological; older patient; placebo controlled study; pressure; randomized placebo controlled trial; secondary outcome; ziprasidone

DESCRIPTION (provided by applicant): The long-term objective of the proposed MIND-USA (Modifying the Impact of ICU-Induced Neurological Dysfunction-USA) Study is to define the role of antipsychotics in the management of delirium in vulnerable critically ill patients. We and others have shown that delirium is an independent predictor of more death, longer stay, higher cost, and long-term cognitive impairment often commensurate with moderate dementia. The rapidly expanding aging ICU population is especially vulnerable to develop delirium, with 7 of 10 medical and surgical ICU patients developing this organ dysfunction. Antipsychotics are the first-line pharmacological agents recommended to treat delirium, and over the past 30 years they gained widespread use in hospitalized patients globally prior to adequate testing of efficacy and safety for this indication. Haloperidol, the most commonly chosen antipsychotic, is used by over 80% of ICU doctors for delirium, while atypical antipsychotics are prescribed by 40%. Antipsychotics safety concerns include lethal cardiac arrhythmias, extrapyramidal symptoms, and the highly publicized increased mortality associated with their use in non-ICU geriatric populations. The overarching hypothesis is that administration of typical and atypical antipsychotics-haloperidol and ziprasidone, in this case-to critically ill patients with delirium will improve short- and long-term clinical outcomes. Aim 1 will determine whether haloperidol or ziprasidone will increase days alive without acute brain dysfunction (referred to as delirium/coma-free days or DCFDs) over a 14-day period compared with placebo and compared to one another. Aim 2 will determine whether haloperidol or ziprasidone will improve 30-day, 90-day, and 1-year survival compared with placebo and compared to one another. Aim 3 will determine whether haloperidol or ziprasidone will reduce ICU length of stay compared with placebo and compared to one another. Aim 4 will determine whether haloperidol or ziprasidone will reduce the incidence, severity, and/or duration of long-term neuropsychological dysfunction and improve quality of life at 90-day and 1-year follow-up compared with placebo and compared to one another. To address these Aims, we will conduct this multi-center, double blind, randomized, placebo-controlled investigation in 876 critically ill, delirious medical/surgical ICU patients who are (a) on mechanical ventilation or non-invasive positive pressure ventilation or (b) in shock on vasopressors. In each group (haloperidol, ziprasidone, and placebo), 292 patients will be enrolled and treated until delirium has resolved for 48 hours or to 14 days (whichever occurs first) and followed for 1 year. We will monitor many safety parameters such as cardiac dysrhythmias and extrapyramidal symptoms. This study will have adequate power to detect the effect of antipsychotics in 4 important subgroups including age >65 years, severity of illness (APACHE II > 25), severe sepsis at enrollment, and medical vs. surgical ICU patients, and a hypothesis generating analysis of patients with pre- existing cognitive impairment. PUBLIC HEALTH RELEVANCE: Millions of critically ill patients every year develop confusion (delirium) while in Intensive Care Units (ICUs), and though a large portion of these patients go undetected and untreated, ICU teams most often use typical and atypical antipsychotics to treat such patients despite no support from placebo-controlled trials. The MIND-USA trial will be the first study ever to answer the question of whether haloperidol or an atypical antipsychotic (ziprasidone) is better or worse than a placebo as treatment for delirious medical and surgical ICU patients. This investigation will determine if either haloperidol or ziprasidone shorten delirium duration, improve survival, affect length of stay in the hospital, or improve long-term brain function and quality of life at 1-year follow-up.

描述（由申请人提供）：拟议的 MIND-USA（改变 ICU 引起的神经功能障碍的影响 - 美国）研究的长期目标是确定抗精神病药物在治疗脆弱危重患者谵妄中的作用。我们和其他人已经证明，谵妄是更多死亡、更长住院时间、更高费用和长期认知障碍的独立预测因素，通常与中度痴呆相称。迅速扩大的 ICU 人口老龄化特别容易发生谵妄，每 10 名内科和外科 ICU 患者中就有 7 名出现这种器官功能障碍。抗精神病药是推荐用于治疗谵妄的一线药物，在过去 30 年中，在对该适应症的有效性和安全性进行充分测试之前，它们在全球住院患者中得到了广泛使用。氟哌啶醇是最常用的抗精神病药物，超过 80% 的 ICU 医生使用它来治疗谵妄，而 40% 的 ICU 医生则使用非典型抗精神病药物。抗精神病药物的安全性问题包括致命的心律失常、锥体外系症状，以及广为人知的与在非 ICU 老年人群中使用抗精神病药物相关的死亡率增加。总体假设是，对患有谵妄的危重患者施用典型和非典型抗精神病药物（本例中为氟哌啶醇和齐拉西酮）将改善短期和长期临床结果。目标 1 将确定与安慰剂相比以及相互比较，氟哌啶醇或齐拉西酮是否会在 14 天的时间内增加没有急性脑功能障碍的存活天数（称为无谵妄/昏迷天数或 DCFD）。目标 2 将确定氟哌啶醇或齐拉西酮与安慰剂相比以及相互比较是否会改善 30 天、90 天和 1 年生存率。目标 3 将确定与安慰剂相比以及相互比较，氟哌啶醇或齐拉西酮是否会缩短 ICU 住院时间。目标 4 将确定与安慰剂相比，氟哌啶醇或齐拉西酮是否会降低长期神经心理功能障碍的发生率、严重程度和/或持续时间，并改善 90 天和 1 年随访时的生活质量。为了实现这些目标，我们将对 876 名危重、精神错乱的内科/外科 ICU 患者进行这项多中心、双盲、随机、安慰剂对照调查，这些患者 (a) 正在接受机械通气或无创正压通气，或 (b) 正在接受血管加压药休克。在每组（氟哌啶醇、齐拉西酮和安慰剂）中，将招募 292 名患者并接受治疗，直至谵妄在 48 小时或 14 天（以先发生者为准）内消失，并随访 1 年。我们将监测许多安全参数，例如心律失常和锥体外系症状。这项研究将有足够的能力来检测抗精神病药物在 4 个重要亚组中的作用，包括年龄 >65 岁、疾病严重程度 (APACHE II > 25)、入组时严重败血症、内科 ICU 患者与外科 ICU 患者，以及对先前存在认知障碍的患者进行分析的假设。 公共卫生相关性：每年有数百万危重患者在重症监护病房 (ICU) 中出现精神错乱（谵妄），尽管其中很大一部分患者未被发现和治疗，但 ICU 团队最常使用典型和非典型抗精神病药物来治疗此类患者，尽管没有安慰剂对照试验的支持。 MIND-USA 试验将是第一个回答氟哌啶醇或非典型抗精神病药（齐拉西酮）作为治疗神志不清的内科和外科 ICU 患者是否比安慰剂更好或更差的问题的研究。这项研究将确定氟哌啶醇或齐拉西酮是否可以缩短谵妄持续时间、提高生存率、影响住院时间或在一年随访时改善长期脑功能和生活质量。