Strategies for Persistent Agitated Delirium in Palliative Care

姑息治疗中持续性激越性谵妄的策略

• 批准号: 10319942
• 负责人: David Hui
• 金额: $ 43.44万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319942
• 关键词: Achievement; Acute; Address; Advanced Malignant Neoplasm; Adverse effects; Affect; Age; Agitation; Antipsychotic Agents; Benzodiazepines; Biological Markers; Cancer Patient; Caregivers; Characteristics; Clinical; Clinical Trials; Combined Modality Therapy; Complex; Consent; Coupled; Data; Decision Making; Delirium; Delusions; Distress; Dose; Double-Blind Method; Effectiveness; Enrollment; Frequencies; Goals; Hallucinations; Haloperidol; Health Professional; Hour; Hyperactivity; Interleukin-10; Interleukin-6; Interleukin-8; Intervention; Intervention Studies; Lorazepam; Mission; Monitor; Nurses; Outcome; Outcome Measure; Palliative Care; Participant; Patient Care; Patient Monitoring; Patients; Pharmaceutical Preparations; Physicians; Placebos; Prediction of Response to Therapy; Proxy; Public Health; Quality of life; Questionnaires; Randomized Controlled Trials; Research; Role; Rotation; Scheme; Sedation procedure; Severities; Standardization; Symptoms; Syndrome; Testing; Therapeutic; Time; Titrations; United States National Institutes of Health; Withdrawal; arm; effective therapy; end of life; end of life care; evidence base; experience; high risk; improved; innovation; intervention effect; neuropsychiatry; novel; novel marker; novel strategies; novel therapeutics; palliate; palliation; palliative; patient population; patient-clinician communication; predictive marker; response; response biomarker; sex; treatment effect; treatment strategy

PROJECT SUMMARY Delirium is the most common and distressing neuropsychiatric syndrome in cancer patients. It has a negative effect on symptom assessment, patient-clinician communication, decision making, and survival. Approximately 50% of patients with hyperactive or mixed delirium continue to experience agitation despite low-dose haloperidol, which can be particularly distressing to patients and caregivers. Neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal may provide good control of agitation. However, no delirium trials have ever been completed to directly compare these options; such trials are urgently needed to improve the quality of life of patients with this devastating syndrome. Our long-term goal is to develop evidence-based therapy for the palliation of delirium in cancer patients. The proposed study is a high-impact, 4-arm, multi-center, double-blind, double-dummy, randomized controlled trial to compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal in the treatment of persistent agitated delirium in cancer patients admitted to acute palliative care units (APCUs). We hypothesize that benzodiazepine rotation and combination therapy are particularly effective against agitated delirium. The primary specific aim of this study is to compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on the change in Richmond Agitation Sedation Scale (RASS) over 24 hours in patients who did not experience a response to low-dose haloperidol. The second aim is to compare the effects of these treatments on (1) rescue medication use, (2) the proportion of patients in the target RASS range, (3) perceived comfort by caregivers and bedside nurses, (4) delirium-related distress in caregivers and nurses, (5) achievement of the proxy comfort goal, (6) symptom expression, (7) delirium severity, (8) adverse effects, and (9) quality of end-of-life care. The third aim is to identify novel predictive markers of response to haloperidol and lorazepam. After obtaining surrogate consent, we will administer the study medications under a titration scheme and monitor the participants closely until discharge. This study is highly innovative because (1) multiple previously untested treatment strategies are studied, (2) the outcome measures (e.g., proxy comfort goals) are novel, (3) biomarkers are included as potential predictors of treatment response, (4) the patient population (i.e., short survival) is unique, and (5) the study setting (i.e., the APCU) is distinctive. Successful completion of this definitive study will identify the optimal strategy to reduce agitation, improve patient comfort, and palliate delirium-related distress; provide timely data to address the ongoing debate regarding the proper use of haloperidol and lorazepam in delirium; inform novel strategies to monitor patients with delirium; and stimulate further studies to identify better strategies to palliate persistent agitation and improve patients' quality of life.

项目摘要 del妄是癌症患者中最常见和令人痛苦的神经精神综合征。它有负 对症状评估，患者临床沟通，决策和生存的影响。大约 尽管低剂量 氟哌啶醇，这对患者和看护者可能特别令人痛苦。神经诱导剂量升级， 苯二氮卓旋转，联合疗法和神经诱发的戒断可能可以很好地控制 搅动。但是，从未完成过直接比较这些选择的ir妄试验。这样的试验 迫切需要改善这种毁灭性综合征患者的生活质量。 我们的长期目标是为癌症患者的del妄抚摸基于证据的治疗。 拟议的研究是一项高影响力，4臂，多中心，双盲，双重，随机控制的 试验以比较神经诱导剂量升级，苯二氮卓旋转，联合治疗和 在接受急性的癌症患者的持续躁动del妄治疗持续的躁动del妄时，神经肌酸性戒断。 姑息治疗单元（APCU）。我们假设苯二氮卓旋转和联合疗法是 特别有效地抵抗躁动的ir妄。这项研究的主要目的是比较 神经摄影剂量升级，苯二氮卓旋转，联合疗法和神经摄取的戒断 在没有经历的患者中，在24小时内，里士满搅动镇静量表（RASS）的变化 对低剂量氟哌啶醇的反应。第二个目的是比较这些处理对（1）救援的影响 使用药物，（2）目标RASS范围内的患者比例，（3）护理人员感知的舒适感 和床头护士，（4）与护理人员和护士的ir妄有关的困扰，（5）代理 舒适目标，（6）症状表达，（7）ir妄严重性，（8）不良影响和（9）寿命终止的质量 关心。第三个目的是确定对氟哌啶醇和劳拉西m的反应的新颖预测标记。后 获得替代同意书，我们将根据滴定计划管理研究药物，并监视 参与者紧密直至出院。 这项研究具有很高的创新性，因为（1）研究了多个先前未经测试的治疗策略， （2）结果指标（例如，代理舒适目标）是新颖的，（3）生物标志物被包括在内 治疗反应的预测因素，（4）患者人群（即短期生存）是独一无二的，（5）研究 设置（即APCU）是独特的。成功完成这项确定的研究将确定最佳 减少躁动，改善患者舒适并抑制与ir妄相关的困扰的策略；提供及时的数据 解决有关在del妄中适当使用氟哌啶醇和劳拉西m的持续辩论；告知小说 监测ir妄患者的策略；并刺激进一步的研究以确定更好的策略以抑制 持续的搅动并改善患者的生活质量。