Haloperidol vs Olanzapine for the Management of ICU Delirium

This study has been terminated.
Sponsor:
Collaborator:
Dalhousie University
Information provided by (Responsible Party):
Richard Hall, Capital District Health Authority, Canada
ClinicalTrials.gov Identifier:
NCT00833300
First received: January 30, 2009
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention
Delirium
Agitation
Drug: Haloperidol
Drug: Olanzapine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Haloperidol vs Olanzapine for the Management of ICU Delirium: A Randomized Clinical Trial

Resource links provided by NLM:


Further study details as provided by Capital District Health Authority, Canada:

Primary Outcome Measures:
  • Resolution of delirium as indicated by an Intensive Care Delirium Screening Checklist score of less than 4 [ Time Frame: Every 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Delirium free days (i.e. time from resolution of delirium to ICU discharge) [ Time Frame: Every 24 hours ] [ Designated as safety issue: No ]
  • Incidence of treatment failure at 48 hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Requirement for rescue medication [ Time Frame: Every 24 hours ] [ Designated as safety issue: No ]
  • Type of rescue medication [ Time Frame: Every 24 hours ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: Time of death ] [ Designated as safety issue: No ]
  • If on mechanical ventilation at time delirium develops, duration of mechanical ventilation [ Time Frame: Every 24 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: June 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Haldol
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00833300

Locations
Canada, Nova Scotia
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
Sponsors and Collaborators
Richard Hall
Dalhousie University
Investigators
Principal Investigator: Richard Hall, MD, FRCPC, FCCP Capital District Health Authority, Canada
  More Information

Publications:

Responsible Party: Richard Hall, Dr. Richard Hall MD FRCPC FCCP, Capital District Health Authority, Canada
ClinicalTrials.gov Identifier: NCT00833300     History of Changes
Other Study ID Numbers: CDHA-RS/2009-001, Control No.:121747, File No.: 9427-C2659-22C
Study First Received: January 30, 2009
Last Updated: August 2, 2012
Health Authority: Canada: Health Canada

Keywords provided by Capital District Health Authority, Canada:
Delirium
Agitation
Intensive Care
Critical Care
Antipsychotics
Olanzapine
Haloperidol

Additional relevant MeSH terms:
Delirium
Psychomotor Agitation
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dyskinesias
Psychomotor Disorders
Haloperidol
Olanzapine
Haloperidol decanoate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014