Trazodone vs Quetiapine for ICU Delirium

(TraQ Trial)

Overseen By Catherine M Kuza, MD, FASA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Southern California

Must not be taking: Benzodiazepines, Alpha-2 agonists

Disqualifiers: Substance abuse, Psychosis, Arrhythmia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of trazodone, quetiapine, and a placebo in treating ICU delirium. ICU delirium can cause confusion, hallucinations, and sleep disturbances, particularly in post-surgery patients. The trial will assess the duration and severity of delirium and the quality of sleep with each treatment. It is suitable for individuals in the surgical ICU for over 24 hours who exhibit delirium symptoms, such as combativeness or hallucinations, and require medication for management. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, aiming to understand their benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications that interact with trazodone or quetiapine.

What is the safety track record for trazodone, quetiapine, and placebo?

Research has shown that trazodone is often used to address sleep problems and might also aid in managing ICU delirium, a condition where patients become confused or have trouble thinking clearly. Some studies indicate that trazodone can quickly reduce delirium symptoms. Additionally, trazodone is generally considered safe for sleep issues, which supports its safety for treating delirium.

For quetiapine, studies suggest it can help manage delirium by reducing confusion and restlessness. Research indicates that short-term use of quetiapine in critically ill patients does not cause serious side effects, making it a promising option for managing delirium without major safety concerns.

Both medications have been used successfully in ICU settings, and the studies mentioned report no major safety issues. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for ICU delirium because they offer potentially safer and more effective alternatives to standard antipsychotics. Quetiapine, a treatment already used in some cases, is being closely compared to trazodone, which is traditionally used for sleep disorders and depression. Trazodone may offer a gentler approach by potentially causing fewer side effects like excessive sedation or cardiovascular issues, which are concerns with typical antipsychotic treatments. This trial aims to explore whether these drugs can manage delirium symptoms more efficiently without the drawbacks of current options.

What evidence suggests that this trial's treatments could be effective for ICU delirium?

In this trial, participants will receive either trazodone or quetiapine to manage ICU delirium. Previous studies have shown that trazodone can improve sleep quality, potentially shortening the duration and reducing the severity of ICU delirium. Quetiapine, in contrast, helps reduce the duration of delirium and calm agitation in ICU patients. Specifically, it has been found to speed up recovery from delirium, especially when combined with other treatments like haloperidol. Both trazodone and quetiapine show promise in managing ICU delirium, with trazodone focusing on better sleep and quetiapine on reducing agitation and delirium symptoms. ^{1 3 4 5 6}

Who Is on the Research Team?

Catherine M Kuza, MD, FASA

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

Adults over 18 in the surgical ICU with delirium, needing medication as decided by their doctor. They must be able to give consent and not have conditions like severe heart issues, liver disease, certain mental health disorders, or be at risk of interactions with the study drugs.

Inclusion Criteria

I have ICU delirium needing medication, confirmed by a CAM-ICU score.

I have been in the surgical ICU for more than a day.

Written informed consent obtained from the patient or their surrogate decision maker

Exclusion Criteria

No signed written informed consent by patient or their surrogate decision maker

I am currently experiencing severe withdrawal symptoms from alcohol or drugs that need treatment.

I have had a type of irregular heartbeat called ventricular arrhythmia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Daily throughout the study period

Daily screening on rounds

Treatment

Participants receive randomized treatment with trazodone, quetiapine, or placebo for ICU delirium

14 days

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Regular assessments

Long-term follow-up

Assessment of long-term cognitive function, depression, anxiety, PTSD, and quality of life

Up to 6 months post-randomization

Assessments at 1, 3, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Quetiapine
• Trazodone

Trial Overview

The trial tests if trazodone is better than quetiapine or a placebo for treating ICU delirium. It looks at how long delirium lasts, mortality rates, hospital stay length, ventilator days needed, complications and sleep quality among patients.

How Is the Trial Designed?

Group I: Trazodone Experimental Treatment 1 Intervention

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

Group II: Quetiapine Active Control 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

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

Quetiapine is already approved in United States, European Union for the following indications:

Approved in United States as Seroquel for:

• Bipolar disorder (depressive and manic episodes)
• Schizophrenia
• Major depressive disorder

Approved in European Union as Seroquel for:

• Schizophrenia
• Bipolar disorder (manic episodes)
• Major depressive episodes in bipolar disorder

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

In a study involving 286 patients with schizophrenia, high-dose quetiapine (up to 750 mg/d) significantly reduced positive symptoms compared to placebo, demonstrating its efficacy as an antipsychotic.

Quetiapine was well tolerated, showing a favorable safety profile without causing extrapyramidal symptoms or significant changes in blood parameters, suggesting it is a safe treatment option for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. Small, JG., Hirsch, SR., Arvanitis, LA., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/19915454/

Efficacy and safety of quetiapine in critically ill patients with ...

Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12028096/

The Role of Quetiapine in Treating Delirium in Critical Care ...

Quetiapine seems to be a reasonable option for managing delirium in ICU patients, showing promising results in reducing both delirium duration and agitation.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05307003

Trazodone vs. Quetiapine for the Treatment of ICU Delirium

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 ...

4.

preprints.org

preprints.org/manuscript/202409.2341/v1

Quetiapine in the ICU: A Paradigm Shift from Sedation to ...

Overall, quetiapine proves to be a valuable tool in critical care, offering effective management for insomnia, agitation, and delirium while ...

5.

researchgate.net

researchgate.net/publication/390923311_The_Role_of_Quetiapine_in_Treating_Delirium_in_Critical_Care_Settings_A_Narrative_Review

The Role of Quetiapine in Treating Delirium in Critical Care ...

Among the pharmacological options, quetiapine has gained attention for its use in ICU patients with delirium. Compared to first-generation ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/26469214/

Evaluation of the Safety of Quetiapine in Treating Delirium in ...

In this population of critically ill youth, short-term use of quetiapine as treatment for delirium appears to be safe, without serious adverse events.