RCT: Trazodone vs Quetiapine vs Placebo for Treating ICU Delirium (TraQ)

NCT05085808 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: APP-20-01962
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Delirium; Morality; Quality of Life; Psych; Treatment Side Effects

Keywords

delirium; quetiapine; trazodone; critical care; ICU delirium

Outcome Measures

Primary Outcomes (1)

• Delirium duration using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) tool

  days

  14 days

Secondary Outcomes (16)

• ICU length of stay

  14 days

• hospital length of stay

  14 days

• mechanical ventilator duration

  14 days

• in-hospital mortality

  14 days

• 28-day mortality

  28 days

Study Arms (3)

Quetiapine

ACTIVE COMPARATOR

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

Drug: Quetiapine

Trazodone

EXPERIMENTAL

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

Drug: Trazodone

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Trazodone DRUG

Trazodone will be administered to ICU patients who need pharmacological intervention for delirium, if they are randomized to the trazodone arm.

Also known as: Desyrel

Trazodone

Quetiapine DRUG

Quetiapine will be administered to ICU patients who need pharmacological intervention for delirium, if they are randomized to the quetiapine arm.

Also known as: Seroquel

Quetiapine

Placebo DRUG

Placebo will be administered to ICU patients who need pharmacological intervention for delirium, if they are randomized to the placebo arm.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>=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

You may not qualify if:

• 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)
• Pregnancy/lactation

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

Keck Hospital of the University of Southern California

Los Angeles, California, 90033, United States

Location

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MeSH Terms

Conditions

Delirium

Interventions

Trazodone; Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridones; Pyridines; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Catherine M Kuza, MD, FASA

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology and Critical Care

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 20, 2021
• Study Start (Estimated): March 1, 2028
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)