Haloperidol and Lorazepam in Controlling Symptoms of Persistent Agitated Delirium in Patients With Advanced Cancer Undergoing Palliative Care

NCT ID: NCT03743649

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-17

Study Completion Date

2026-12-31

Brief Summary

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This phase II/IIII trial studies how well haloperidol and lorazepam work in controlling symptoms of persistent agitated delirium in patients with cancer that has spread to other places in the body undergoing palliative care. Haloperidol and lorazepam may help in controlling symptoms of agitated delirium in patients with cancer and may lessen any distress that their caregivers may be experiencing.

Detailed Description

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Primary Objectives:

I. To compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on the change in the Richmond Agitation Sedation Scale (RASS) score over 24 hours in patients admitted to an acute palliative care unit (APCU) who do not respond to low-dose haloperidol

Secondary Objectives:

I. To compare the effects of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on (1) rescue medication use; (2) the proportion of patients in the target RASS range (defined as RASS between -2 and 0) as well as the proportion of patients achieving treatment response (defined as RASS reduction of ≥ 1.5 points); (3) perceived comfort as assessed by caregivers and bedside nurses; (4) delirium-related distress in caregivers and nurses (Delirium Experience Questionnaire); (5) achievement of the proxy comfort goal; (6) symptom expression (Edmonton Symptom Assessment Scale \[ESAS\]); (7) delirium severity (Memorial Delirium Assessment Scale \[MDAS\]); (8) adverse effects; and (9) quality of end-of-life care.

II. To identify novel predictive markers of response to haloperidol and lorazepam.

OUTLINE: Patients are randomized to 1 of 4 groups.

GROUP I: Patients receive haloperidol intravenously (IV) over 3-15 minutes every 4 hours and then every hour as needed and placebo IV every 4 hours and then every hour as needed until discharge from palliative care unit.

GROUP II: Patients receive lorazepam IV over 3-15 minutes every 4 hours and then every hour as needed and placebo IV every 4 hours and then every hour as needed until discharge from palliative care unit.

GROUP III: Patients receive haloperidol IV over 3-15 minutes every 4 hours and then every hour as needed and lorazepam IV over 3-15 minutes every 4 hours and then every hour as needed until discharge from palliative care unit.

GROUP IV: Patients receive two different placebos IV every 4 hours. Patients then receive placebo IV and lorazepam IV over 3-15 minutes every hour as needed until discharge from palliative care unit.

Conditions

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Delirium Locally Advanced Malignant Neoplasm Metastatic Malignant Neoplasm Recurrent Malignant Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group I (haloperidol, placebo)

Patients receive haloperidol IV over 3-15 minutes every 4 hours and then every hour as needed and placebo IV every 4 hours and then every hour as needed until discharge from palliative care unit.

Group Type EXPERIMENTAL

Haloperidol

Intervention Type DRUG

Given IV

Placebo

Intervention Type OTHER

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Group II (lorazepam, placebo)

Patients receive lorazepam IV over 3-15 minutes every 4 hours and then every hour as needed and placebo IV every 4 hours and then every hour as needed until discharge from palliative care unit.

Group Type EXPERIMENTAL

Lorazepam

Intervention Type DRUG

Given IV

Placebo

Intervention Type OTHER

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Group III (haloperidol, lorazepam)

Patients receive haloperidol IV over 3-15 minutes every 4 hours and then every hour as needed and lorazepam IV over 3-15 minutes every 4 hours and then every hour as needed until discharge from palliative care unit.

Group Type EXPERIMENTAL

Haloperidol

Intervention Type DRUG

Given IV

Lorazepam

Intervention Type DRUG

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Group IV (placebo, lorazepam)

Patients receive two different placebos IV every 4 hours. Patients then receive placebo IV and lorazepam IV over 3-15 minutes every hour as needed until discharge from palliative care unit.

Group Type EXPERIMENTAL

Lorazepam

Intervention Type DRUG

Given IV

Placebo

Intervention Type OTHER

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Haloperidol

Given IV

Intervention Type DRUG

Lorazepam

Given IV

Intervention Type DRUG

Placebo

Given IV

Intervention Type OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Haldol McN-JR-1625 R 1625 R-1625 Ativan placebo therapy PLCB sham therapy Quality of Life Assessment

Eligibility Criteria

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Inclusion Criteria

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-5 criteria
4. \[Patients\] Hyperactive or mixed delirium with RASS ≥1\* in the past 24 h despite efforts to treat potential underlying causes
5. \[Patients\] On scheduled haloperidol for delirium (≤8 mg in the past 24 h) or required ≥4 mg of rescue haloperidol for agitation in the past 24 h
6. \[Patients\] Age 18 years or older
7. \[Caregivers\] Patient's spouse, adult child, sibling, parent, other relative, or significant other (partner as defined by patient)
8. \[Caregivers\] Age 18 years or older

Exclusion Criteria

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, Alzheimer's or Lewy body dementia
4. \[Patients\] History of prolonged QTc or QTcF interval (\>500 ms)† if documented by most recent ECG within the past month
5. \[Patients\] History of hypersensitivity to haloperidol or lorazepam
6. \[Patients\] On scheduled lorazepam within the past 48 h
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Hui

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Hosptial de Cancer de Barretos

Barretos, São Paulo, Brazil

Site Status

Countries

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United States Brazil

References

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Hui D, De La Rosa A, Tsai JS, Cheng SY, Del Fabbro E, Thomas Kuzhiyil AT, Rowe K, Azhar A, Nguyen T, Tang M, Yao CA, Huang HL, Peng JK, Hu WY, Admane S, Dev R, Chen M, Bramati P, Shete S, Bruera E. Proportional Sedation for Persistent Agitated Delirium in Palliative Care: A Randomized Clinical Trial. JAMA Oncol. 2025 Sep 1;11(9):1031-1043. doi: 10.1001/jamaoncol.2025.2212.

Reference Type DERIVED
PMID: 40742738 (View on PubMed)

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

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NCI-2018-02438

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-0706

Identifier Type: OTHER

Identifier Source: secondary_id

2018-0706

Identifier Type: -

Identifier Source: org_study_id