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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

Is quetiapine effective for treating ICU delirium?

Research shows that quetiapine can help resolve delirium symptoms faster than a placebo in ICU patients, making it a potentially effective option for treating ICU delirium. ^{1 2 3 4 5}

Is quetiapine safe for treating ICU delirium?

Quetiapine has been shown to be well-tolerated in patients with delirium, with studies indicating it is generally safe for use in medically ill patients. ^{1 3 6 7 8}

How does the drug quetiapine differ from other drugs for ICU delirium?

Quetiapine is unique for ICU delirium treatment because it is an atypical antipsychotic that can lead to quicker resolution of delirium compared to placebo, and it is generally well-tolerated with a low risk of causing movement-related side effects (extrapyramidal symptoms). Unlike the standard treatment haloperidol, quetiapine has a broader efficacy due to its action on both dopamine and serotonin receptors. ^{1 2 3 4 9}

Research Team

Catherine M Kuza, MD, FASA

Principal Investigator

University of Southern California

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of Delirium With Quetiapine. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Antipsychotics for the prevention and treatment of delirium in the intensive care unit: what is their role? [2015]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of the feasibility of switching from immediate release quetiapine to extended release quetiapine fumarate in stable outpatients with schizophrenia. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Quetiapine in refractory hyperactive and mixed intensive care delirium: a case series. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Focus on quetiapine. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Quetiapine extended release for the treatment of bipolar disorder. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Update on extended release quetiapine fumarate in schizophrenia and bipolar disorders. [2021]