Haloperidol vs Olanzapine for the Management of ICU Delirium

Delirium Clinical Trial

Official title:

Haloperidol vs Olanzapine for the Management of ICU Delirium: A Randomized Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00833300
• Other study ID #: CDHA-RS/2009-001
• Secondary ID: Control No.:1217
• Status: Terminated
• Phase: N/A
• First received: January 30, 2009
• Last updated: August 2, 2012
• Start date: June 2008
• Est. completion date: November 2011

Study information

• Verified date: August 2012
• Source: Nova Scotia Health Authority
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this randomized clinical trial is to determine whether haloperidol is superior to olanzapine for the treatment of ICU acquired delirium. The hypothesis is that haloperidol is in fact superior to olanzapine in treating ICU acquired delirium and sustaining delirium free time.

Description:

Delirium is defined as a disturbance of consciousness characterized by an acute onset of impaired cognitive function. Although delirium is thought to be common in the Intensive Care Unit (ICU) there are few studies that have evaluated its incidences, risks and outcomes. It has been associated with increased morbidity, and mortality and increased cost to the healthcare system. In addition to the uncertainty of the incidence of ICU delirium, there is a lack of information about the effects that certain pharmacological treatments have on delirious patients.

The standard pharmacological treatments for ICU acquired delirium are haloperidol and olanzapine as they have been shown to be equivalent in reducing its incidence. However, optimal dose and regimen have not been well defined.

The rationale for this study is to determine whether haloperidol is superior to olanzapine in the treatment of ICU acquired delirium. A secondary objective is to determine the most appropriate dosing regimen for the treatmet. The role of alternative agents quetiapine, risperidone, loxapine and methotrimeprazine will also be examined in a preliminary analysis.

Patients who develop agitation or delirium as defined by an Intensive Care Delirium Checklist (ICDSC) score of greater than or equal to 4 meeting all the inclusion criteria and no exclusion criteria will be eligible for randomization. Once randomized they will be screened for ongoing agitation and delirium as well prolongation of the QTc interval greater than 440 msec, development of extrapyramidal symptoms and development of a seizure disorder.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 200
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients who are 18 years or older who are admitted for more than 24 hours to the ICU.

• Patients screened for delirium using the ICDSC with a score greater than or equal to 4 or with clinical manifestations of delirium.

Exclusion Criteria:

• Patients unlikely to survive 24 hours.

• Patients with a primary neurologic reason (i.e. stroke, dementia-related psychosis) for ICU admission.

• Patients with QTc interval greater than 440 msec.

• Pregnant patients.

• Patients who are breast feeding.

• Patients in whom haloperidol, or olanzapine is contraindicated.

• Patients allergic to haloperidol, olanzapine, quetiapine, risperidone, loxapine or methotrimeprazine.

• Patients who do not have a urinary catheter.

• Patients who have received haloperidol, olanzapine, quetiapine, risperidone, loxapine or methotrimeprazine within 14 days.

• Patients unable to undergo assessment (i.e. patients with developmental disability or mental incapacity prior to ICU admission).

• Prolonged (greather than 24 hours) comatose patients who have a defined structural reason for their decreased level of consciousness.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Agitation
• Delirium

Intervention

Drug:
• Haloperidol
2.5 mg-10 mg IV q6h for 24 hours and 2.5 mg-5 mg IV prn, up to 40mg in 24 hours. Reassess in 24 hours. Delirium absent - Continue dose for 24 hours then discontinue. Delirium present - Increase dose 5 mg-10 mg IV q6h for 24 hours and 2.5 mg-5 mg IV prn, up to 40 mg in 24 hours. Reassess in 24 hours. Delirium absent - Continue dose for 24 hours then discontinue. Delirium present - Discontinue current drug therapy and select one of: Quetiapine up to 100 mg/day Risperidone up to 6 mg/day Loxapine up to 50 mg/day Methotrimeprazine up to 75 mg/day Reassess in 24 hours. Delirium absent - Continue for 24 hours then discontinue. Delirium present - Treatment at discretion of attending physician.
• Olanzapine
2.5 mg-10 mg po/ng/og bid and 2.5 mg po/ng/og prn, up to 20 mg in 24 hours. Reassess in 24 hours. Delirium absent - Continue dose for 24 hours then discontinue. Delirium present - Increase dose 5 mg-10 mg bid and 2.5 mg po/ng/og prn, up to 20 mg in 24 hours. Reassess in 24 hours. Delirium absent - Continue dose for 24 hours then discontinue. Delirium present - Discontinue current drug therapy and select one of: Quetiapine up to 100 mg/day Risperidone up to 6 mg/day Loxapine up to 50 mg/day Methotrimeprazine up to 75 mg/day Reassess in 24 hours. Delirium absent - Continue for 24 hours then discontinue. Delirium present - Treatment at discretion of attending physician.

Locations

Country	Name	City	State
Canada	Halifax Infirmary; Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Victoria General Hospital; Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia

Sponsors (2)

Lead Sponsor	Collaborator
Richard Hall	Dalhousie University

Country where clinical trial is conducted

Canada, 

References & Publications (21)

Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001 May;27(5):859-64. — View Citation

Bergeron N, Skrobik Y, Dubois MJ. Delirium in critically ill patients. Crit Care. 2002 Jun;6(3):181-2. Epub 2002 Apr 5. — View Citation

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Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Falk V, Schmitt DV, Mohr FW. Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg. 2004 Jan;127(1):57-64. — View Citation

Devlin JW, Fong JJ, Schumaker G, O'Connor H, Ruthazer R, Garpestad E. Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients. Crit Care Med. 2007 Dec;35(12):2721-4; quiz 2725. — View Citation

Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001 Aug;27(8):1297-304. — View Citation

Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91. — View Citation

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Lacasse H, Perreault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother. 2006 Nov;40(11):1966-73. Epub 2006 Oct 17. Review. — View Citation

Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004 Apr;32(4):955-62. — View Citation

Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007 Jan;33(1):66-73. Epub 2006 Nov 11. — View Citation

Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6. — View Citation

Plaschke K, von Haken R, Scholz M, Engelhardt R, Brobeil A, Martin E, Weigand MA. Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s). Intensive Care Med. 2008 Mar;34(3):431-6. Epub 2007 Nov 9. — View Citation

Rea RS, Battistone S, Fong JJ, Devlin JW. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy. 2007 Apr;27(4):588-94. Review. — View Citation

Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004 Mar;30(3):444-9. Epub 2003 Dec 19. — View Citation

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of delirium as indicated by an Intensive Care Delirium Screening Checklist score of less than 4		Every 24 hours	No
Secondary	Delirium free days (i.e. time from resolution of delirium to ICU discharge)		Every 24 hours	No
Secondary	Incidence of treatment failure at 48 hours		48 hours	No
Secondary	Requirement for rescue medication		Every 24 hours	No
Secondary	Type of rescue medication		Every 24 hours	No
Secondary	Mortality		Time of death	No
Secondary	If on mechanical ventilation at time delirium develops, duration of mechanical ventilation		Every 24 hours	No