The MIND USA Study

美国 MIND 研究

• 批准号: 8431390
• 负责人: E Wesley ELY
• 金额: $ 152.86万
• 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 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8431390
• 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; public health relevance; 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.

描述（由申请方提供）：拟定的MIND-USA（修改ICU诱导的神经功能障碍的影响-USA）研究的长期目标是确定抗精神病药物在管理脆弱重症患者谵妄中的作用。我们和其他人已经表明，谵妄是一个独立的预测更多的死亡，更长的停留，更高的成本，和长期的认知障碍往往与中度痴呆症相称。迅速扩大的老龄化ICU人群特别容易发生谵妄，10名内科和外科ICU患者中有7名发生这种器官功能障碍。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，在对该适应症的疗效和安全性进行充分检测之前，抗精神病药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，而非典型抗精神病药物则占40%。抗精神病药物的安全性问题包括致死性心律失常、锥体外系症状以及在非ICU老年人群中使用抗精神病药物导致的死亡率增加。首要的假设是，典型和非典型抗精神病药物的管理氟哌啶醇和齐拉西酮，在这种情况下，危重患者谵妄将改善短期和长期的临床结果。目的1将确定与安慰剂相比以及与其他药物相比，氟哌啶醇或齐拉西酮是否会增加14天内无急性脑功能障碍的生存天数（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氟哌啶醇或齐拉西酮之间的比较是否会缩短ICU住院时间。目的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，并在90天和1年随访时改善生活质量。为了实现这些目标，我们将在876例危重、谵妄内科/外科ICU患者中进行这项多中心、双盲、随机、安慰剂对照研究，这些患者（a）接受机械通气或无创正压通气或（B）接受血管加压药治疗的休克。在每组（氟哌啶醇、齐拉西酮和安慰剂）中，将入组292例患者并接受治疗，直至谵妄消退48小时或14天（以先发生者为准），并随访1年。我们将监测许多安全性参数，如心律失常和锥体外系症状。本研究将有足够的把握度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）、入组时的严重脓毒症和内科与外科ICU患者，以及对既存认知障碍患者的假设生成分析。