Haloperidol With or Without Chlorpromazine in Treating Delirium in Patients With Advanced, Metastatic, or Recurrent Cancer

M.D. Anderson Cancer Center

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Locally Advanced Malignant Neoplasm; Delirium; Advanced Malignant Neoplasm; Recurrent Malignant Neoplasm; Metastatic Malignant Neoplasm

Treatments: Drug: Haloperidol; Drug: Chlorpromazine; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03021486

NCI-2017-01065 (Registry Identifier)

2016-0687 (Other Identifier)

R21NR016736 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This randomized phase II/III trial studies how well haloperidol with or without chlorpromazine works in treating delirium in patients with cancer that has spread to other parts of the body or has come back. Haloperidol and chlorpromazine may control the symptoms of delirium (loss of contact with reality) in patients with cancer.

Full description

PRIMARY OBJECTIVES:

I. Assess the within-arm effect of haloperidol dose escalation, rotation to chlorpromazine, and combination therapy on agitation intensity (Richmond Agitation Sedation Scale [RASS]) over 24 hours in patients admitted to an acute palliative care unit (APCU) who did not experience a response to low-dose haloperidol.

SECONDARY OBJECTIVES:

I. Obtain preliminary estimates of the effects of haloperidol dose escalation, rotation to chlorpromazine, and combination therapy on (1) the proportion of patients with target RASS -2 to 0, (2) delirium-related distress in nurses and caregivers (delirium experience questionnaire), (3) symptom expression (Edmonton Symptom Assessment Scale), (4) delirium severity (Memorial Delirium Assessment Scale), (5) the need for neuroleptics, (6) delirium recall (Delirium Recall Questionnaire), (7) adverse effects and (8) quality of end-of-life (Quality of Death and Dying questionnaire) over time.

II. Obtain preliminary estimates of the between-arm effect size among haloperidol dose escalation, rotation to chlorpromazine, and combination therapy in the first 24 hours.

III. To assess caregiver and nurse preferences regarding proxy sedation goals. IV. To examine the feasibility of novel measures for the assessment of agitation with continuous video monitoring.

OUTLINE: Patients are randomized to 1 of 3 groups.

GROUP I: Patients receive haloperidol intravenously (IV) over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

GROUP II: Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

GROUP III: Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

1. [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
2. [Patients] Admitted to the acute palliative care unit
3. [Patients] Delirium as per DSM-V criteria (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5))
4. [Patients] Hyperactive or mixed delirium with RASS >/=1 in the past 24 h (RASS>/=+1 indicates any degree of restlessness. In the electronic medical record nursing note, this behavior would be indicated by any documentation of "restless", "agitated", "hyperactive", "pulling on devices/IV" or similar wording).
5. [Patients] On scheduled haloperidol for delirium (</=8 mg in the past 24 h) or rescue haloperidol of >/=4 mg for restlessness/agitation in the past 24 h
6. [Patients] Age 18 years or older
7. [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
8. [Family Caregivers] Age 18 years or older

Exclusion:

1. [Patients] History of myasthenia gravis or acute narrow angle glaucoma
2. [Patients] History of neuroleptic malignant syndrome or active seizure disorder (with seizure episode within the past week)
3. [Patients] History of Parkinson's disease or Alzheimer's dementia
4. [Patients] History of prolonged QTc interval (>500 ms) if documented by ECG within the past month
5. [Patients] History of hypersensitivity to haloperidol or chlorpromazine
6. [Patients] On scheduled chlorpromazine within the past 48 h

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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70 participants in 3 patient groups

Group I (haloperidol)

Experimental group

Description:

Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Treatment:

Other: Quality-of-Life Assessment

Other: Questionnaire Administration

Drug: Haloperidol

Group II (chlorpromazine)

Experimental group

Description:

Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Treatment:

Other: Quality-of-Life Assessment

Other: Questionnaire Administration

Drug: Chlorpromazine

Group III (haloperidol, chlorpromazine)

Experimental group

Description:

Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Treatment:

Other: Quality-of-Life Assessment

Other: Questionnaire Administration

Drug: Chlorpromazine

Drug: Haloperidol