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...
Date First Received: January 30, 2009
Last Updated: September 10, 2009
Verified by: Capital District Health Authority, Canada, January 2009
Clinical Trial Phase: N/A | Start Date: June 2008
Overall Status: Recruiting
Estimated Enrollment: 200
Brief Summary
Official Title: “Haloperidol vs Olanzapine for the Management of ICU Delirium: A Randomized Clinical Trial”
Intervention(s):
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 Type: Interventional
Study Design: Treatment, Randomized, Single Blind (Subject), Parallel Assignment, Efficacy Study
Study Primary Completion Date: December 2009
Detailed Clinical Trial 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.
Intervention(s) in this Clinical Trial
- 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: Quetiapine up to 100 mg/day Risperidone up to 6 mg/day Loxapine up to 50 mg/day 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.
- 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: Quetiapine up to 100 mg/day Risperidone up to 6 mg/day Loxapine up to 50 mg/day 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.
Arms, Groups and Cohorts in this Clinical Trial
- Active Comparator: 1
- Haloperidol
- Active Comparator: 2
- Olanzapine
Outcome Measures for this Clinical Trial
Primary Measures
- Resolution of delirium as indicated by an Intensive Care Delirium Screening Checklist score of less than 4
- Time Frame: Every 24 hours
Safety Issue?: No
- Time Frame: Every 24 hours
Secondary Measures
- Delirium free days (i.e. time from resolution of delirium to ICU discharge)
- Time Frame: Every 24 hours
Safety Issue?: No
- Time Frame: Every 24 hours
- Incidence of treatment failure at 48 hours
- Time Frame: 48 hours
Safety Issue?: No
- Time Frame: 48 hours
- Requirement for rescue medication
- Time Frame: Every 24 hours
Safety Issue?: No
- Time Frame: Every 24 hours
- Type of rescue medication
- Time Frame: Every 24 hours
Safety Issue?: No
- Time Frame: Every 24 hours
- Mortality
- Time Frame: Time of death
Safety Issue?: No
- Time Frame: Time of death
- If on mechanical ventilation at time delirium develops, duration of mechanical ventilation
- Time Frame: Every 24 hours
Safety Issue?: No
- Time Frame: Every 24 hours
Criteria for Participation in this Clinical Trial
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.
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: Capital District Health Authority, Canada
Overall Clinical Trial Officials and Contacts
Richard Hall, MD, FRCPC, FCCP Principal Investigator Capital District Health Authority, Canada
Overall Contact: Kristi Abraham, BSc.Phm, ACPR 902-473-2057 kristi.abraham@cdha.nshealth.ca
Related Publications
References
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Additional Information
Information obtained from ClinicalTrials.gov on February 08, 2010
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00833300
Study ID Number: CDHA-RS/2009-001
ClinicalTrials.gov Identifier: NCT00833300
Health Authority: Canada: Health Canada
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
