Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer

NCT ID: NCT01949662

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2026-01-01

Brief 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.

Detailed 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.

Conditions

Advanced Cancers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Lorazepam + Haloperidol

Participants given a single dose of lorazepam 3 mg by vein, in addition to a standardized dose of haloperidol 8 mg/day by vein, while in palliative care unit. Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete

Group Type: EXPERIMENTAL

Lorazepam

Intervention Type: DRUG

3 mg by vein one time only.

Haloperidol decanoate

Intervention Type: DRUG

8 mg/day by vein.

Questionnaires

Intervention Type: BEHAVIORAL

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

Placebo + Haloperidol

Participants receive placebo, preservative free 0.9% normal saline, by vein plus a standardized dose of haloperidol 8 mg/day by vein, while in palliative care unit. Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo consisting of preservative free 0.9% normal saline given one time by vein.

Haloperidol decanoate

Intervention Type: DRUG

8 mg/day by vein.

Questionnaires

Intervention Type: BEHAVIORAL

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

Interventions

Lorazepam

3 mg by vein one time only.

Intervention Type: DRUG

Placebo

Placebo consisting of preservative free 0.9% normal saline given one time by vein.

Intervention Type: DRUG

Haloperidol decanoate

8 mg/day by vein.

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Surveys

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Hui, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Hui D, Frisbee-Hume S, Wilson A, Dibaj SS, Nguyen T, De La Cruz M, Walker P, Zhukovsky DS, Delgado-Guay M, Vidal M, Epner D, Reddy A, Tanco K, Williams J, Hall S, Liu D, Hess K, Amin S, Breitbart W, Bruera E. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017 Sep 19;318(11):1047-1056. doi: 10.1001/jama.2017.11468.

Reference Type: DERIVED

PMID: 28975307 (View on PubMed)

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center

Other Identifiers

NCI-2013-02351

Identifier Type: REGISTRY

Identifier Source: secondary_id

1R21CA186000-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2013-0345

Identifier Type: -

Identifier Source: org_study_id