Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

January 30, 2009
August 2, 2012
June 2008
November 2011   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00833300 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Haloperidol vs Olanzapine for the Management of ICU Delirium
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
  • Delirium
  • Agitation
  • 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
  • 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
    Intervention: Drug: Haloperidol
  • Active Comparator: 2
    Olanzapine
    Intervention: Drug: Olanzapine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
200
November 2011
November 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00833300
CDHA-RS/2009-001, Control No.:121747, File No.: 9427-C2659-22C
Not Provided
Richard Hall, Capital District Health Authority, Canada
Richard Hall
Dalhousie University
Principal Investigator: Richard Hall, MD, FRCPC, FCCP Capital District Health Authority, Canada
Capital District Health Authority, Canada
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP