Haloperidol vs Olanzapine for the Management of ICU Delirium

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

Sponsors

Lead Sponsor: Richard Hall

Collaborator: Dalhousie University

Source Nova Scotia Health Authority
Brief 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.

Detailed 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.

Overall Status Terminated
Start Date 2008-06-01
Completion Date 2011-11-01
Primary Completion Date 2011-11-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Resolution of delirium as indicated by an Intensive Care Delirium Screening Checklist score of less than 4 Every 24 hours
Secondary Outcome
Measure Time Frame
Delirium free days (i.e. time from resolution of delirium to ICU discharge) Every 24 hours
Incidence of treatment failure at 48 hours 48 hours
Requirement for rescue medication Every 24 hours
Type of rescue medication Every 24 hours
Mortality Time of death
If on mechanical ventilation at time delirium develops, duration of mechanical ventilation Every 24 hours
Enrollment 200
Condition
Intervention

Intervention Type: Drug

Intervention Name: Haloperidol

Description: 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.

Arm Group Label: 1

Other Name: Haldol

Intervention Type: Drug

Intervention Name: Olanzapine

Description: 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.

Arm Group Label: 2

Eligibility

Criteria:

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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Richard Hall, MD, FRCPC, FCCP Principal Investigator Nova Scotia Health Authority
Location
Facility:
Halifax Infirmary; Queen Elizabeth II Health Sciences Centre | Halifax, Nova Scotia, Canada
Victoria General Hospital; Queen Elizabeth II Health Sciences Centre | Halifax, Nova Scotia, Canada
Location Countries

Canada

Verification Date

2012-08-01

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Nova Scotia Health Authority

Investigator Full Name: Richard Hall

Investigator Title: Dr. Richard Hall MD FRCPC FCCP

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: 1

Type: Active Comparator

Description: Haloperidol

Label: 2

Type: Active Comparator

Description: Olanzapine

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Single (Participant)

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