Trazodone vs. Quetiapine for the Treatment of ICU Delirium: A Prospective Observational Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- coma-free days
研究概览
简要总结
This is a single-center, prospective observational pilot study. The objective of this study is to evaluate the effectiveness of trazodone as compared to quetiapine, in the management of ICU delirium in adult (>=18 years old) surgical and medical ICU patients. The investigators will compare outcomes such as delirium duration, delirium-free days, coma-free days, in-hospital mortality, 28-day mortality, hospital length of stay (LOS), ICU LOS, mechanical ventilator days, complications, adverse effects, rescue medication use, delirium symptom severity, sleep duration, and sleep quality among participants receiving trazodone or quetiapine. The investigators hypothesize participants receiving trazodone will be associated with a shorter duration of delirium, decreased delirium severity, and improved sleep quality compared to participants receiving quetiapine.
详细描述
This is a single-center, double-blind randomized, placebo-controlled pilot trial comparing trazodone, quetiapine, and placebo for the treatment of ICU delirium in adult patients admitted to the medical and surgical ICU at Keck Hospital of the University of Southern California.
The purpose of this study is to determine the effectiveness of trazodone and quetiapine for the treatment of ICU delirium, and their effects on patient outcomes. Since the incidence of ICU delirium is high and has profound negative ramifications on survival, long-term outcomes, cognitive function, in addition to placing a heavy burden on the healthcare system resources and costs, effective delirium treatment strategies are desperately needed. Trazodone is a medication that has promise in delirium treatment, but there is currently insufficient literature to recommend its routine use. The investigators' main objective is to determine if trazodone is an effective and safe treatment option for the management of ICU delirium, and if it results in shorter delirium duration and improved outcomes compared to participants receiving quetiapine.
Subject screening:
All patients will be screened for study eligibility daily on rounds throughout the study period. Patients eligible for the study will be enrolled in the study after receiving a patient information sheet. As this is part of standard of care and the medications would be administered regardless of study participation, written informed consent will be waived.
ICU nurses will assess all patients for delirium at least every 12 hours, using the CAM-ICU tool , in accordance with the standard of care in the surgical ICU (that is, this assessment would be performed regardless of the study).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>=18-years-old
- •Admitted to the surgical ICU for >24 hours
- •Diagnosis of ICU delirium defined by positive CAM-ICU score AND exhibiting symptomatic delirium (i.e., combative, pulling at lines, a danger to self or others, inability to sleep, hallucinations, etc.), thus, requiring the need for pharmacologic intervention as determined by the attending intensivist
- •Receiving either quetiapine or trazodone for the treatment of delirium
排除标准
- •Presence of an acute neurologic condition (i.e., acute cerebrovascular accident, intracranial tumor, traumatic brain injury, etc.) on ICU admission. History of stroke or other neurological condition(s) without cognitive impairment is not an exclusion criterion.
- •Pregnancy/lactation
- •History of ventricular arrhythmia including torsade de pointes or second- and third-degree heart block
- •Allergy/hypersensitivity reaction to trazodone and/or quetiapine
- •Diagnosis of dementia
- •History of neuroleptic malignant syndrome and/or serotonin syndrome
- •Diagnosis of Parkinson's disease or parkinsonism (also referred to as hypokinetic rigidity syndrome)
- •Schizophrenia or other psychotic disorder
- •Patients in whom CAM-ICU cannot be performed to screen for delirium (i.e., acute encephalopathy, mental retardation, vegetative state, deaf, blind, etc.) [reversible coma (that is, not caused by traumatic brain injury, cerebrovascular accident, or intracranial tumor), defined as RASS -4 or -5 at any point through one ICU day, is NOT an exclusion criterion.]
- •Inability to speak or understand English
- •Expected to die or transfer out of the ICU within 24 hours
- •Acute alcohol or substance abuse withdrawal symptoms/syndrome (i.e., delirium tremens) requiring treatment/intervention (e.g, implementation of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol, benzodiazepines, alpha-2 agonist, etc.)
- •Prolonged QTc syndrome AND/OR prolonged QT-interval (QTc>450 ms for men, and >460 ms for women on ECG performed within 1 month of ICU admission or day of study enrollment)
- •Active psychosis [defined as distortion or loss of contact with reality, delusions and/or
- •hallucinations (without insight), and/or thought disorder-must be diagnosed by a psychiatrist]
- •Patients taking medications with known interactions with either trazodone and/or quetiapine per Pharmacy (e.g., MAOIs (monoamine oxidase inhibitors), SSRIs (selective serotonin reuptake inhibitors; etc.)
- •Acute encephalopathy (i.e., hepatic, uremic, etc.)
- •Seizure disorder
- •Myocardial infarction (MI) within the past 30 days
- •Tardive dyskinesia
- •Symptomatic hyponatremia
- •Terminal state
- •Diagnosis of liver disease
- •Patients who are strict NPO (nil per os), are a high aspiration risk (defined as frequent nausea/vomiting, ileus, gastric dysmotility disorder, uncontrolled gastroesophageal reflux disease, weakness/deconditioning, diabetes with gastroparesis, not tolerating full tube feeds if being enterally fed (high residual gastric volume >500 cc), elderly patients with waxing/waning mental status), have dysphagia, and/or have difficulty swallowing capsules or solutions as determined by speech therapist
- •Currently enrolled and participating in another interventional study
- •Patients who have received both trazodone and quetiapine in the management of their delirium
- •Patients who have had a history of serotonin syndrome
- •Patients who were enrolled in the study once, are not eligible for re-enrollment if they are readmitted to the ICU
研究组 & 干预措施
Quetiapine
Patients diagnosed with delirium who received quetiapine for treatment.
- Start study medication at 25 mg daily PO ; may increase to BID (twice a day) or TID (three times a day) if RASS>=2 or rescue medication must be given; thereafter, if med is TID, dose can be increased by increment of 50 mg q12 hr if RASS>=2 and/or >1 dose of rescue medication is given within 24 hours [max dose 200 mg/day]
- dose can be reduced/discontinued per discretion of ICU attending if delirium improving, patient experiences AE (adverse effects) likely related to study drug, after 14 days of treatment, or patient is discharged from ICU
- dose should be held if RASS is -3 to -5/comatose/unresponsive or sudden acute change in mental status
干预措施: Quetiapine (Drug)
Trazodone
Patients diagnosed with delirium who received trazodone for treatment.
- Start study medication at 25 mg daily PO ; may increase to BID or TID if RASS>=2 or rescue medication must be given; thereafter, if med is TID, dose can be increased by increment of 50 mg q12 hr if RASS>=2 and/or >1 dose of rescue medication is given within 24 hours [max dose 200 mg/day]
- dose can be reduced/discontinued per discretion of ICU attending if delirium improving, patient experiences AE likely related to study drug, after 14 days of treatment, or patient is discharged from ICU
- dose should be held if RASS is -3 to -5/comatose/unresponsive or sudden acute change in mental status
干预措施: Trazodone (Drug)
结局指标
主要结局
coma-free days
时间窗: 14 days
days
delirium duration using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) tool
时间窗: 14 days
days
delirium-free days
时间窗: 14 days
days
次要结局
- in-hospital mortality(365 days)
- mechanical ventilator days(14 days)
- adverse effects of study drugs(14 days)
- ICU length of stay(14 days)
- total hospital length of stay(14 days)
- 28-day mortality(28 days)
- complications(14 days)
- post-discharge depression(1-month post-hospital discharge)
- use of rescue medications(14 days)
- delirium severity(14 days)
- sleep quality(14 days)
- post-discharge anxiety(1-month post-hospital discharge)
研究者
Catherine Kuza, MD
Assistant Professor of Anesthesiology
University of Southern California