Haloperidol vs Olanzapine for the Management of ICU Delirium

August 2, 2012 updated by: Richard Hall

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Halifax Infirmary; Queen Elizabeth II Health Sciences Centre
      • Halifax, Nova Scotia, Canada
        • Victoria General Hospital; Queen Elizabeth II Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 2
Olanzapine
Drug: 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:

    1. Quetiapine up to 100 mg/day
    2. Risperidone up to 6 mg/day
    3. Loxapine up to 50 mg/day
    4. 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.
Other Names:
  • Zyprexa
  • Zyprexa Zydis
  • Novo-Olanzapine
  • PMS-Olanzapine
Active Comparator: 1
Haloperidol
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:

    1. Quetiapine up to 100 mg/day
    2. Risperidone up to 6 mg/day
    3. Loxapine up to 50 mg/day
    4. 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.
Other Names:
  • Haldol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Resolution of delirium as indicated by an Intensive Care Delirium Screening Checklist score of less than 4
Time Frame: Every 24 hours
Every 24 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Delirium free days (i.e. time from resolution of delirium to ICU discharge)
Time Frame: Every 24 hours
Every 24 hours
Incidence of treatment failure at 48 hours
Time Frame: 48 hours
48 hours
Requirement for rescue medication
Time Frame: Every 24 hours
Every 24 hours
Type of rescue medication
Time Frame: Every 24 hours
Every 24 hours
Mortality
Time Frame: Time of death
Time of death
If on mechanical ventilation at time delirium develops, duration of mechanical ventilation
Time Frame: Every 24 hours
Every 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Richard Hall

Collaborators

Dalhousie University

Investigators

  • Principal Investigator: Richard Hall, MD, FRCPC, FCCP, Nova Scotia Health Authority

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

January 30, 2009

First Submitted That Met QC Criteria

January 30, 2009

First Posted (Estimate)

February 2, 2009

Study Record Updates

Last Update Posted (Estimate)

August 3, 2012

Last Update Submitted That Met QC Criteria

August 2, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDHA-RS/2009-001
  • Control No.:121747
  • File No.: 9427-C2659-22C

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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