Haloperidol vs Olanzapine for the Management of ICU Delirium

NCT ID: NCT00833300

Last Updated: 2012-08-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2011-11-30

Brief Summary

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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

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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.

Conditions

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Delirium Agitation

Keywords

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Delirium Agitation Intensive Care Critical Care Antipsychotics Olanzapine Haloperidol

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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1

Haloperidol

Group Type ACTIVE_COMPARATOR

Haloperidol

Intervention Type DRUG

* 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.

2

Olanzapine

Group Type ACTIVE_COMPARATOR

Olanzapine

Intervention Type DRUG

* 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Haldol Zyprexa Zyprexa Zydis Novo-Olanzapine PMS-Olanzapine

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dalhousie University

OTHER

Sponsor Role collaborator

Richard Hall

OTHER

Sponsor Role lead

Responsible Party

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Richard Hall

Dr. Richard Hall MD FRCPC FCCP

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Richard Hall, MD, FRCPC, FCCP

Role: PRINCIPAL_INVESTIGATOR

Nova Scotia Health Authority

Locations

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Halifax Infirmary; Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

Victoria General Hospital; Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

Countries

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Canada

References

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Other Identifiers

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Control No.:121747

Identifier Type: -

Identifier Source: secondary_id

File No.: 9427-C2659-22C

Identifier Type: -

Identifier Source: secondary_id

CDHA-RS/2009-001

Identifier Type: -

Identifier Source: org_study_id