Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer

Advanced Cancers Clinical Trial

Official title:

A Preliminary Double-Blind Randomized Controlled Trial of Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer Admitted to a Palliative Care Unit

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01949662
• Other study ID #: 2013-0345
• Secondary ID: NCI-2013-023511R
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 2014
• Est. completion date: January 1, 2026

Study information

• Verified date: February 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well haloperidol with or without lorazepam works in reducing confusion, disorientation, and inability to think or remember clearly (delirium) in patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Palliative therapy with haloperidol and lorazepam may reduce symptoms of delirium and help patients with advanced cancer live more comfortably. It is not yet known whether lorazepam may be an effective treatment for delirium when given with haloperidol.

Description:

PRIMARY OBJECTIVES:

I. To compare the effect of single dose lorazepam and placebo as an adjuvant to haloperidol on the intensity of agitation (Richmond Agitation Sedation Scale) over 8 hours.

II. To assess the within-arm effect of single-dose lorazepam or placebo, as an adjuvant agent with haloperidol, on agitation intensity (Richmond Agitation Sedation Scale) over 8 hours in patients admitted to an acute palliative care unit.

SECONDARY OBJECTIVES:

I. To compare the effect of single dose lorazepam and placebo as an adjuvant to haloperidol on (1) delirium related distress in nurses and caregivers, (2) delirium duration, (3) need for rescue doses of neuroleptics, (4) delirium recall, (5) symptom expression (Edmonton Symptom Assessment Scale), (6) communicative capacity, (7) adverse effects, (8) discharge outcomes, and (9) survival in cancer patients.

II. To evaluate proportion of patients who consent and are randomized to study however drop out before being treated or before finishing 8-hour Richmond Agitation Sedation Scale (RASS) assessment; and the reasons of drop-outs will be documented and reported.

III. To explore the changes in biomarker levels in saliva samples (salivary cortisol, cholinesterase, C-reactive protein, interleukin-1 beta, -6, and -10) over time and in association with delirium severity.

IV. To examine the inter-rater reliability of RASS in the Acute Palliative Care Unit (APCU) setting between the bedside nurse and the research nurse at the time of study enrollment.

V. To conduct exploratory analyses on RASS as an outcome. VI. To examine the association among rescue medication use, RASS and perceived comfort by the nurses and caregivers.

VII. To examine the proportion of patients enrolled onto the delirium trial who achieved control of agitation and did not require the randomized study medication.

VIII. To identify patient factors associated with control of agitated delirium.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive lorazepam intravenously (IV) over 1-2 minutes and haloperidol IV every 6 hours or every 1 hour if needed.

ARM II: Patients receive placebo IV over 1-2 minutes and haloperidol IV every 6 hours or every 1 hour if needed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 93
• Est. completion date: January 1, 2026
• Est. primary completion date: August 26, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• PATIENTS:

• Diagnosis of advanced cancer (defined as locally advanced, metastatic, recurrent, or incurable disease)

• Admitted to Acute Palliative Care Unit (APCU)

• Delirium as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV- TR) criteria

• Hyperactive/mixed delirium with RASS >= 2 in the last 24 hours

• On scheduled haloperidol of =< 8 mg in the last 24 hours

• Legally authorized representative consent

• FAMILY CAREGIVERS:

• Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)

• Age 18 or older

• At the patient's bedside at least 4 hours each day during patient delirium episode

• Patients and family caregivers able to communicate in English or Spanish

Exclusion Criteria:

• PATIENTS

• History of myasthenia gravis or acute narrow angle glaucoma

• History of neuroleptic malignant syndrome

• History of Parkinson's disease or dementia

• Uncontrolled seizure disorder

• History of hypersensitivity to haloperidol or benzodiazepine

• On regular doses of benzodiazepine or chlorpromazine within the past 48 hours

• Previously documented and persistent corrected QT (QTc) prolongation (> 500 ms)

• Heart failure exacerbation at the time of enrollment

Related Conditions & MeSH terms

• Advanced Cancers
• Delirium
• Neoplasms

Intervention

Drug:
• Lorazepam
3 mg by vein one time only.
• Placebo
Placebo consisting of preservative free 0.9% normal saline given one time by vein.
• Haloperidol decanoate
8 mg/day by vein.

Behavioral:
• Questionnaires
Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete.

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points	The primary outcome was change in Richmond Agitation-Sedation Scale score from baseline to 8 hours after treatment administration. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.	Baseline to 8 hours
Primary	Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points	Absolute score of Richmond Agitation-Sedation Scale at 8 hr, points. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.	8 hours
Secondary	Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min	Change in Richmond Agitation-Sedation Scale score from baseline to 30 min. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.	Baseline to 30 minutes
Secondary	Number of Participants With Richmond Agitation-Sedation Scale Score >=1 Within 8 hr	Number of participants with Richmond Agitation-Sedation Scale score >=1 within 8 hr. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.	Baseline to 8 hours

External Links

•   University of Texas MD Anderson Cancer Center