The MIND USA Study

美国 MIND 研究

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：拟议的思维usa的长期目标（修改ICU诱导的神经功能障碍-USA的影响）研究是确定抗精神病药在弱势批评患者中del妄管理中的作用。我们和其他人表明，妄想是更多死亡，更长的停留，更高的成本和长期认知障碍的独立预测指标，通常与适度的痴呆症相称。迅速扩大的ICU人群尤其容易发生del妄，其中10名医疗和ICU患者中有7名患有这种器官功能障碍。抗精神病药是建议治疗der妄的一线药理剂，在过去的30年中，他们在全球住院的患者中广泛使用了这种适应症的疗效和安全性。氟哌啶醇是最常见的抗精神病药，超过80％的ICU医生用于ir妄，而非典型抗精神病药则为40％。抗精神病药的安全问题包括致命的心律失常，锥体外症状，以及与非ICU老年人种群使用相关的高度宣传的死亡率。总体假设是，在这种情况下，典型和非典型的抗精神病药 - 升 - 甲丙啶和Ziprasidone的给药会改善患有ir妄的严重患者，将改善短期和长期的临床结果。 AIM 1将确定氟哌啶醇或Ziprasidone是否会在14天的时间内与安慰剂相比，在14天的时间内是否会增加天生的活力（称为del妄/无昏迷天或DCFDS），并彼此相比。 AIM 2将确定与安慰剂相比，氟哌啶醇或Ziprasidone是否会改善30天，90天和1年的生存率，并相互比较。 AIM 3将确定与安慰剂相比，氟哌啶醇或Ziprasidone是否会降低ICU的住院时间，并相互比较。 AIM 4将确定氟哌啶醇或Ziprasidone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，并改善与安慰剂相比，在90天和1年的随访中，并改善了生活质量。为了解决这些目标，我们将在876例重病，狂热的医疗/外科ICU患者中进行此多中心，双盲，随机，安慰剂对照的研究，这些患者（A）（a）在机械通气或非侵入性正压通风或（b）对vasopressors的冲击中。在每组（氟哌啶醇，Ziprasidone和安慰剂）中，将接受292例患者的治疗，直到del妄已解决48小时或14天（以先到者为单位），然后持续1年。我们将监测许多安全参数，例如心脏异常和锥体外症状。这项研究将具有足够的能力来检测4个重要亚组的抗精神病药作用，包括年龄> 65岁，疾病严重程度（Apache II> 25），入学率严重的败血症以及医学与外科ICU患者以及对患者的现有认知障碍患者的假设分析。