NCT00833300

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jun 2008

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2008

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

January 30, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 2, 2009

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2011

Completed
Last Updated

August 3, 2012

Status Verified

August 1, 2012

Enrollment Period

3.4 years

First QC Date

January 30, 2009

Last Update Submit

August 2, 2012

Conditions

DeliriumAgitation

Keywords

DeliriumAgitationIntensive CareCritical CareAntipsychoticsOlanzapineHaloperidol

Outcome Measures

Primary Outcomes (1)

  • Resolution of delirium as indicated by an Intensive Care Delirium Screening Checklist score of less than 4

    Every 24 hours

Secondary Outcomes (6)

  • 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

  • +1 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

Haloperidol

Drug: Haloperidol

2

ACTIVE COMPARATOR

Olanzapine

Drug: Olanzapine

Interventions

HaloperidolDRUG

* 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.

Also known as: Haldol
1
OlanzapineDRUG

* 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.

Also known as: Zyprexa, Zyprexa Zydis, Novo-Olanzapine, PMS-Olanzapine
2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Halifax Infirmary; Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Victoria General Hospital; Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Related Publications (21)

  • Bergeron N, Skrobik Y, Dubois MJ. Delirium in critically ill patients. Crit Care. 2002 Jun;6(3):181-2. doi: 10.1186/cc1482. Epub 2002 Apr 5.

    PMID: 12133171BACKGROUND

  • Lacasse H, Perreault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother. 2006 Nov;40(11):1966-73. doi: 10.1345/aph.1H241. Epub 2006 Oct 17.

    PMID: 17047137BACKGROUND

  • Jaber S, Chanques G, Altairac C, Sebbane M, Vergne C, Perrigault PF, Eledjam JJ. A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes. Chest. 2005 Oct;128(4):2749-57. doi: 10.1378/chest.128.4.2749.

    PMID: 16236951BACKGROUND

  • Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007 Jan;33(1):66-73. doi: 10.1007/s00134-006-0399-8. Epub 2006 Nov 11.

    PMID: 17102966BACKGROUND

  • Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. doi: 10.1097/00003246-200201000-00020. No abstract available.

    PMID: 11902253BACKGROUND

  • Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004 Apr;32(4):955-62. doi: 10.1097/01.ccm.0000119429.16055.92.

    PMID: 15071384BACKGROUND

  • Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6. doi: 10.1097/00000542-200601000-00005.

    PMID: 16394685BACKGROUND

  • Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004 Mar;30(3):444-9. doi: 10.1007/s00134-003-2117-0. Epub 2003 Dec 19.

    PMID: 14685663BACKGROUND

  • Plaschke K, von Haken R, Scholz M, Engelhardt R, Brobeil A, Martin E, Weigand MA. Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s). Intensive Care Med. 2008 Mar;34(3):431-6. doi: 10.1007/s00134-007-0920-8. Epub 2007 Nov 9.

    PMID: 17994221BACKGROUND

  • Devlin JW, Fong JJ, Schumaker G, O'Connor H, Ruthazer R, Garpestad E. Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients. Crit Care Med. 2007 Dec;35(12):2721-4; quiz 2725. doi: 10.1097/01.ccm.0000292011.93074.82.

    PMID: 18074477BACKGROUND

  • Rea RS, Battistone S, Fong JJ, Devlin JW. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy. 2007 Apr;27(4):588-94. doi: 10.1592/phco.27.4.588.

    PMID: 17381385BACKGROUND

  • Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001 May;27(5):859-64. doi: 10.1007/s001340100909.

    PMID: 11430542BACKGROUND

  • Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91. doi: 10.1001/jama.289.22.2983.

    PMID: 12799407BACKGROUND

  • Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974 Jul 13;2(7872):81-4. doi: 10.1016/s0140-6736(74)91639-0. No abstract available.

    PMID: 4136544BACKGROUND

  • Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001 Aug;27(8):1297-304. doi: 10.1007/s001340101017.

    PMID: 11511942BACKGROUND

  • Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29.

    PMID: 3928249BACKGROUND

  • Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Falk V, Schmitt DV, Mohr FW. Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg. 2004 Jan;127(1):57-64. doi: 10.1016/s0022-5223(03)01281-9.

    PMID: 14752413BACKGROUND

  • Korevaar JC, van Munster BC, de Rooij SE. Risk factors for delirium in acutely admitted elderly patients: a prospective cohort study. BMC Geriatr. 2005 Apr 13;5:6. doi: 10.1186/1471-2318-5-6.

    PMID: 15826320BACKGROUND

  • Stein LM, Thienhaus OJ. Hearing impairment and psychosis. Int Psychogeriatr. 1993 Spring;5(1):49-56. doi: 10.1017/s1041610293001383.

    PMID: 8499573BACKGROUND

  • Brust JC. Acute neurologic complications of drug and alcohol abuse. Neurol Clin. 1998 May;16(2):503-19. doi: 10.1016/s0733-8619(05)70074-8.

    PMID: 9537972BACKGROUND

  • Vincent FM. The neuropsychiatric complications of corticosteroid therapy. Compr Ther. 1995 Sep;21(9):524-8.

    PMID: 8565441BACKGROUND

MeSH Terms

Conditions

DeliriumPsychomotor Agitation

Interventions

HaloperidolOlanzapine

Condition Hierarchy (Ancestors)

ConfusionNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsNeurocognitive DisordersMental DisordersDyskinesiasPsychomotor DisordersAberrant Motor Behavior in DementiaBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

ButyrophenonesKetonesOrganic ChemicalsBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Richard Hall, MD, FRCPC, FCCP

    Nova Scotia Health Authority

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Dr. Richard Hall MD FRCPC FCCP

Study Record Dates

First Submitted

January 30, 2009

First Posted

February 2, 2009

Study Start

June 1, 2008

Primary Completion

November 1, 2011

Study Completion

November 1, 2011

Last Updated

August 3, 2012

Record last verified: 2012-08

Locations

CA(2)