Delirium Clinical Trial
— TQDeliriumOfficial title:
Trazodone vs. Quetiapine for the Treatment of ICU Delirium: A Prospective Observational Pilot Study
NCT number | NCT05307003 |
Other study ID # | HS-22-00540 |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | April 1, 2023 |
Est. completion date | December 2025 |
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.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | December 2025 |
Est. primary completion date | August 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - >=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 Exclusion Criteria: - 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 |
Country | Name | City | State |
---|---|---|---|
United States | Keck Hospital of the University of Southern California | Los Angeles | California |
Lead Sponsor | Collaborator |
---|---|
University of Southern California |
United States,
Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011 Jan;1(1):41-7. doi: 10.1177/1941875210386491. — View Citation
Breitbart W, Gibson C, Tremblay A. The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics. 2002 May-Jun;43(3):183-94. doi: 10.1176/appi.psy.43.3.183. — View Citation
Brummel NE, Girard TD. Preventing delirium in the intensive care unit. Crit Care Clin. 2013 Jan;29(1):51-65. doi: 10.1016/j.ccc.2012.10.007. — View Citation
Collinsworth AW, Priest EL, Campbell CR, Vasilevskis EE, Masica AL. A Review of Multifaceted Care Approaches for the Prevention and Mitigation of Delirium in Intensive Care Units. J Intensive Care Med. 2016 Feb;31(2):127-41. doi: 10.1177/0885066614553925. Epub 2014 Oct 27. — View Citation
Davydow DS. Symptoms of depression and anxiety after delirium. Psychosomatics. 2009 Jul-Aug;50(4):309-16. doi: 10.1176/appi.psy.50.4.309. — View Citation
Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, Robbins T, Garpestad E. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010 Feb;38(2):419-27. doi: 10.1097/CCM.0b013e3181b9e302. — View Citation
Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299. — View Citation
Devlin JW, Skrobik Y, Riker RR, Hinderleider E, Roberts RJ, Fong JJ, Ruthazer R, Hill NS, Garpestad E. Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study. Crit Care. 2011;15(5):R215. doi: 10.1186/cc10450. Epub 2011 Sep 17. — View Citation
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753. — View Citation
Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009 Apr;5(4):210-20. doi: 10.1038/nrneurol.2009.24. — View Citation
Hodgson C, Needham D, Haines K, Bailey M, Ward A, Harrold M, Young P, Zanni J, Buhr H, Higgins A, Presneill J, Berney S. Feasibility and inter-rater reliability of the ICU Mobility Scale. Heart Lung. 2014 Jan-Feb;43(1):19-24. doi: 10.1016/j.hrtlng.2013.11.003. Epub 2013 Nov 19. Erratum In: Heart Lung. 2014 Jul-Aug;43(4):388. — View Citation
Ishii T et al. Retrospective Study of Trazodone Monotherapy Compared with Ramelteon and Trazodone Combination Therapy for the Management of Delirium. J Psychiatry. 2018; 21(3):1-5
Jackson P, Khan A. Delirium in critically ill patients. Crit Care Clin. 2015 Jul;31(3):589-603. doi: 10.1016/j.ccc.2015.03.011. Epub 2015 May 4. — View Citation
Jones C, Griffiths RD, Humphris G, Skirrow PM. Memory, delusions, and the development of acute posttraumatic stress disorder-related symptoms after intensive care. Crit Care Med. 2001 Mar;29(3):573-80. doi: 10.1097/00003246-200103000-00019. — View Citation
Kamdar BB, King LM, Collop NA, Sakamuri S, Colantuoni E, Neufeld KJ, Bienvenu OJ, Rowden AM, Touradji P, Brower RG, Needham DM. The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med. 2013 Mar;41(3):800-9. doi: 10.1097/CCM.0b013e3182746442. — View Citation
Knauert MP, Haspel JA, Pisani MA. Sleep Loss and Circadian Rhythm Disruption in the Intensive Care Unit. Clin Chest Med. 2015 Sep;36(3):419-29. doi: 10.1016/j.ccm.2015.05.008. Epub 2015 Jun 29. — View Citation
Madrid-Navarro CJ, Sanchez-Galvez R, Martinez-Nicolas A, Marina R, Garcia JA, Madrid JA, Rol MA. Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment. Curr Pharm Des. 2015;21(24):3453-68. doi: 10.2174/1381612821666150706105602. — View Citation
Maeda I, Inoue S, Uemura K, Tanimukai H, Hatano Y, Yokomichi N, Amano K, Tagami K, Yoshiuchi K, Ogawa A, Iwase S; Phase-R Delirium Study Group. Low-Dose Trazodone for Delirium in Patients with Cancer Who Received Specialist Palliative Care: A Multicenter Prospective Study. J Palliat Med. 2021 Jun;24(6):914-918. doi: 10.1089/jpm.2020.0610. Epub 2021 Feb 11. — View Citation
Mangan KC, McKinzie BP, Deloney LP, Leon SM, Eriksson EA. Evaluating the risk profile of quetiapine in treating delirium in the intensive care adult population: A retrospective review. J Crit Care. 2018 Oct;47:169-172. doi: 10.1016/j.jcrc.2018.07.005. Epub 2018 Jul 5. — View Citation
Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF Bundle in Critical Care. Crit Care Clin. 2017 Apr;33(2):225-243. doi: 10.1016/j.ccc.2016.12.005. — View Citation
Michaud CJ, Bullard HM, Harris SA, Thomas WL. Impact of Quetiapine Treatment on Duration of Hypoactive Delirium in Critically Ill Adults: A Retrospective Analysis. Pharmacotherapy. 2015 Aug;35(8):731-9. doi: 10.1002/phar.1619. Epub 2015 Aug 4. — View Citation
Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. Erratum In: J Am Geriatr Soc. 2019 Sep;67(9):1991. — View Citation
Okamoto Y, Matsuoka Y, Sasaki T, Jitsuiki H, Horiguchi J, Yamawaki S. Trazodone in the treatment of delirium. J Clin Psychopharmacol. 1999 Jun;19(3):280-2. doi: 10.1097/00004714-199906000-00018. No abstract available. — View Citation
Ospina JP et al. Epidemiology, Mechanisms, Diagnosis, and Treatment of Delirium: A Narrative Review. Clinical Medicine and Therapuetics. 2018;1(1):3-9.
Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372. — View Citation
Popeo DM. Delirium in older adults. Mt Sinai J Med. 2011 Jul-Aug;78(4):571-82. doi: 10.1002/msj.20267. — View Citation
Pulak LM, Jensen L. Sleep in the Intensive Care Unit: A Review. J Intensive Care Med. 2016 Jan;31(1):14-23. doi: 10.1177/0885066614538749. Epub 2014 Jun 10. — View Citation
Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA. 2016 Apr 12;315(14):1460-8. doi: 10.1001/jama.2016.2707. Erratum In: JAMA. 2016 Aug 16;316(7):775. — View Citation
Reznik ME, Slooter AJC. Delirium Management in the ICU. Curr Treat Options Neurol. 2019 Nov 14;21(11):59. doi: 10.1007/s11940-019-0599-5. — View Citation
Richards KC, O'Sullivan PS, Phillips RL. Measurement of sleep in critically ill patients. J Nurs Meas. 2000 Fall-Winter;8(2):131-44. — View Citation
Ringdal GI, Ringdal K, Juliebo V, Wyller TB, Hjermstad MJ, Loge JH. Using the Mini-Mental State Examination to screen for delirium in elderly patients with hip fracture. Dement Geriatr Cogn Disord. 2011;32(6):394-400. doi: 10.1159/000335743. Epub 2012 Feb 1. — View Citation
Roberts DJ, Goralski KB, Renton KW, Julien LC, Webber AM, Sleno L, Volmer DA, Hall RI. Effect of acute inflammatory brain injury on accumulation of morphine and morphine 3- and 6-glucuronide in the human brain. Crit Care Med. 2009 Oct;37(10):2767-74. doi: 10.1097/CCM.0b013e3181b755d5. — View Citation
Salluh JI, Latronico N. Making advances in delirium research: coupling delirium outcomes research and data sharing. Intensive Care Med. 2015 Jul;41(7):1327-9. doi: 10.1007/s00134-015-3864-4. Epub 2015 Jun 3. No abstract available. — View Citation
Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res. 2019 Sep 9;12:1178646919873925. doi: 10.1177/1178646919873925. eCollection 2019. — View Citation
van den Boogaard M, Schoonhoven L, Evers AW, van der Hoeven JG, van Achterberg T, Pickkers P. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med. 2012 Jan;40(1):112-8. doi: 10.1097/CCM.0b013e31822e9fc9. — View Citation
Wada K, Morita Y, Iwamoto T, Mifune Y, Nojima S. First- and second-line pharmacological treatment for delirium in general hospital setting-Retrospective analysis. Asian J Psychiatr. 2018 Feb;32:50-53. doi: 10.1016/j.ajp.2017.11.028. Epub 2017 Dec 5. — View Citation
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83. — View Citation
Zhang H, Lu Y, Liu M, Zou Z, Wang L, Xu FY, Shi XY. Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials. Crit Care. 2013 Mar 18;17(2):R47. doi: 10.1186/cc12566. — View Citation
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x. — View Citation
* Note: There are 39 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | delirium duration using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) tool | days | 14 days | |
Primary | delirium-free days | days | 14 days | |
Primary | coma-free days | days | 14 days | |
Secondary | in-hospital mortality | yes or no | 365 days | |
Secondary | ICU length of stay | days | 14 days | |
Secondary | total hospital length of stay | days | 14 days | |
Secondary | mechanical ventilator days | days | 14 days | |
Secondary | 28-day mortality | yes or no | 28 days | |
Secondary | complications | yes or no | 14 days | |
Secondary | adverse effects of study drugs | yes or no | 14 days | |
Secondary | use of rescue medications | yes or no | 14 days | |
Secondary | delirium severity | Confusion Assessment Method-Severity (CAM-S) long form [0= minimum; 19=maximum; increase in score means worse outcome] | 14 days | |
Secondary | sleep quality | using Richards Campbell Sleep Questionnaire | 14 days | |
Secondary | post-discharge depression | measured using Hospital Anxiety and Depression Scale [ 0=minimum;21=maximum; the higher the score the higher the chance of depression and worse outcome] | 1-month post-hospital discharge | |
Secondary | post-discharge anxiety | measured using Hospital Anxiety and Depression Scale [ 0=minimum;21=maximum; the higher the score the higher the chance of anxiety and worse outcome] | 1-month post-hospital discharge |
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