Comparison of Trazodone vs Quetiapine vs Placebo for the Treatment of ICU Delirium: A Randomized Controlled Trial (The TraQ Study)
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Delirium duration using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) tool
研究概览
简要总结
The objective of this study is to evaluate the effectiveness of trazodone as compared to quetiapine and placebo, in the management of ICU delirium in adult (>=18 years old) surgical ICU patients. The investigators will compare outcomes such as delirium incidence and duration, 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, quetiapine, or placebo. The investigators hypothesize participants receiving trazodone will have a shorter duration of delirium, decreased delirium severity, and improved sleep quality compared to participants receiving quetiapine and placebo.
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 surgical ICU at Keck Hospital of the University of Southern California.
The purpose of this study is to determine the effectiveness of several medications (trazodone, quetiapine and placebo) used 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 and placebo.
Subject screening:
All patients will be screened for study eligibility daily on rounds throughout the study period. Patients eligible for the study will be asked for written informed consent (signed by either the patient or the surrogate decision maker) after admission (even if the patient does not have delirium), or at any point during the ICU course (patient may or may not have a delirium diagnosis at the time of consent).
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
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The only unmasked participant will be the pharmacist (who is not part of the study) who will be preparing and packaging the 3 different study medications. The intensivist, ICU RN, patients, patient's family members/legal representative, and additional study personnel will be masked to the intervention.
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
- •Written informed consent obtained from the patient or their surrogate decision maker.
- •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
排除标准
- •Acute alcohol or substance abuse withdrawal symptoms/syndrome (i.e., delirium tremens) requiring treatment/intervention (i.e., implementation of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol, benzodiazepines, alpha-2 agonist, etc.)
- •Recent torsade de pointes or ventricular arrhythmia
- •Prolonged QTc syndrome AND/OR prolonged QT-interval (QTc>500 ms on baseline EKG, performed on the day of randomization)
- •Active psychosis
- •Patients taking medications with known interactions with either trazodone and/or quetiapine
- •Acute encephalopathy (i.e., hepatic, uremic, etc.)
- •Seizure disorder
- •myocardial infarction (MI) within the past 30 days
- •Tardive dyskinesia
- •Hyponatremia
- •Terminal state
- •Diagnosis of liver disease
- •Patients who are strict NPO, are a high aspiration risk (defined as frequent nausea/vomiting, ileus, gastric dysmotility disorder, uncontrolled GERD, 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 as determined by speech therapist
- •Patients who have enteral access such as a small-bore feeding tube, nasogastric or orogastric tube, or gastrostomy/gastrojejunostomy tube (as these patients will need medications crushed in order to administer via the tube, and the capsules used in this study cannot be crushed)
- •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
- •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/coma, deaf, blind, etc.)
- •Inability to speak or understand English
- •Expected to die or transfer out of the ICU within 24 hours
- •Currently enrolled and participating in another interventional study
- •No signed written informed consent by patient or their surrogate decision maker.
研究组 & 干预措施
Placebo
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: Placebo (Drug)
Trazodone
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)
Quetiapine
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: Quetiapine (Drug)
结局指标
主要结局
Delirium duration using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) tool
时间窗: 14 days
days
次要结局
- hospital length of stay(14 days)
- ICU length of stay(14 days)
- mechanical ventilator duration(14 days)
- in-hospital mortality(14 days)
- complications(14 days)
- sleep quality(14 days)
- 28-day mortality(28 days)
- Long-term cognitive function(up to 6 months post-randomization (measured at 1-, 3-, 6-months post-randomization))
- Long-term depression(up to 6 months post-randomization (measured at 1-, 3-, 6-months post-randomization))
- Long-term anixety(up to 6 months post-randomization (measured at 1-, 3-, 6-months post-randomization))
- discharge disposition(14 days)
- adverse study drug-related reactions(14 days)
- Use of rescue medications(14 days)
- Delirium severity(14 days)
- Long-term PTSD(up to 6 months post-randomization (measured at 1-, 3-, 6-months post-randomization))
- Long-term quality of life(up to 6 months post-randomization (measured at 1-, 3-, 6-months post-randomization))
研究者
Catherine Kuza, MD
Assistant Professor of Anesthesiology and Critical Care
University of Southern California