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Advanced Malignant NeoplasmPhase 2/3NCT03021486

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

A Phase 2/3 study testing Chlorpromazine, Haloperidol and Quality-of-Life Assessment in people with Advanced Malignant Neoplasm and Delirium, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Chlorpromazine, Haloperidol and Quality-of-Life Assessment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
5 Jun 2017to 30 Jun 2027
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
  • [Patients] Admitted to the acute palliative care unit
  • [Patients] Delirium as per DSM-V criteria (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5))
  • [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).
  • [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
  • [Patients] Age 18 years or older
  • [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
  • [Family Caregivers] Age 18 years or older

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Haloperidol and/or Chlorpromazine for Refractory Agitated Delirium in the Palliative Care Unit

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Chlorpromazine, Haloperidol, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Delirium, Neoplasm Metastasis, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChlorpromazineDrug

    Also called Chlor-PZ, Thorazine

    Given IV

  • HaloperidolDrug

    Also called Haldol, McN-JR-1625, R 1625, R-1625

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT03021486
Study groupRoleWhat they receive
Group I (haloperidol)ExperimentalPatients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Receives: Drug: Haloperidol; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Group II (chlorpromazine)ExperimentalPatients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Receives: Drug: Chlorpromazine; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Group III (haloperidol, chlorpromazine)ExperimentalPatients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Receives: Drug: Chlorpromazine; Drug: Haloperidol; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Richmond Agitation Sedation Score (RASS) (0-24h)

    RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The primary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 24 h later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.

    Measured: Time 0 or Baseline and 24 hours after study medication administration

Secondary outcomes (10)

  1. Percentage of Participants With RASS Score -2 to 0

    RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The Secondary outcome was the percentage of participants with target RASS score of -2 to 0 within the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.

    Measured: Time 0 or Baseline and 24 hours later.

  2. Change in RASS Score (0-30 Minutes)

    RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 30 minutes later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit.

    Measured: Time 0 or Baseline and 30 minutes later.

  3. Number of Participants With RASS Score of >=1

    RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was the proportion of breakthrough restlessness participants with a RASS score of >=1 during the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit.

    Measured: 0 or Baseline and 24 hours later

  4. Pattern of Medication Use

    Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.

    Measured: Baseline and 24 hours

  5. Perceived Comfort Level as Assessed by Caregiver

    On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from "strongly agree", "agree", "neutral", "disagree", and "strongly disagree". In this study, "strongly agree" and "agree" were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).

    Measured: Baseline and 24 hour

  6. Perceived Comfort Level as Assessed by Nurse

    On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from "strongly agree", "agree", "neutral", "disagree", and "strongly disagree". In this study, "strongly agree" and "agree" were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated).

    Measured: Baseline and 24 hour

  7. Change in Delirium Experience Questionnaire

    This 14-item questionnaire examines both the recalled frequency of 7 delirium symptoms and associated distress in the rater: disorientation to time, disorientation to place, visual hallucinations, tactile hallucinations, auditory hallucinations, delusional thoughts and psychomotor agitation. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much and 4=extremely distressed. Due to an error in the data collection form, the last category was omitted as a choice and thus the score only ranged from 0 to 3.

    Measured: Baseline and Day 3

  8. Memorial Delirium Assessment Scale (MDAS)

    The Memorial Delirium Assessment Scale (MDAS) is a 10-item clinician-rated assessment scale validated for assessment of delirium in cancer patients. It examines the level of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity and sleep, assigning a score between 0 to 3, for a total score between 0-30. A total score of 13 or higher indicates delirium. We measured the change in Memorial Delirium Rating scale between baseline and 24 hours.

    Measured: Baseline and 24 hours

  9. Edmonton Expression Assessment System, ESAS

    Edmonton Symptom Assessment System (ESAS) has been validated and widely used in different clinical settings, including the acute palliative care unit. It assessed the average symptom intensity of 10 symptoms over the past 24 hours. Each symptom was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). It was measured as change in ESAS as Perceived by Caregivers between baseline and day 1, mean.

    Measured: Baseline and 24 hours

  10. Udvalg for Kliniske Undersogelser, UKU

    We also documented the selected adverse effects associated with neuroleptics using the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale. Specifically, we assessed 8 neurologic symptoms (dystonia, rigidity, hypokinesia/akinesia, hyperkinesia, tremor, akathisia, epileptic seizures, paraesthesias). We are reporting only the neurologic symptoms (tremor and akathisia) that had changes during the study. Each item was assigned a score by the research coordinator 0 (absent) to 3 (most severe) based on symptom severity of the last 3 days.

    Measured: Baseline and 3 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2017 (estimated)
  2. Study start5 Jun 2017
  3. Primary completion5 Jun 2021
  4. Study completion30 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03021486
Sponsor's protocol ID
2016-0687
Other IDs
NCI-2017-01065, 2016-0687, R21NR016736
Status last verified
Sep 2026
First submitted
12 Jan 2017
Last updated
14 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Hui D, De La Rosa A, Wilson A, Nguyen T, Wu J, Delgado-Guay M, Azhar A, Arthur J, Epner D, Haider A, De La Cruz M, Heung Y, Tanco K, Dalal S, Reddy A, Williams J, Amin S, Armstrong TS, Breitbart W, Bruera E. Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial. Lancet Oncol. 2020 Jul;21(7):989-998. doi: 10.1016/S1470-2045(20)30307-7. Epub 2020 May 29.

    PubMed 32479786

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Chlorpromazine, Haloperidol and Quality-of-Life Assessment in people with Advanced Malignant Neoplasm and Delirium, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Richmond Agitation Sedation Score (RASS) (0-24h) (time frame: Time 0 or Baseline and 24 hours after study medication administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03021486, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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