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

NCT03743649 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0706NCI-2018-02438
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in Richmond Agitation Sedation Scale (RASS) score in patients admitted to an acute palliative care unit (APCU)

  The effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal will be compared on the change in the RASS score over 24 hours in patients admitted to an APCU who do not respond to low-dose haloperidol.(RASS between -2 and 0) Will use 2-sided t-tests for four pre-specified paired comparisons, if the required assumptions for this model are met. Non-parametric methods such as Wilcoxon rank-sum test may be used if any assumptions are violated.

  Baseline to 24 hours

Secondary Outcomes (10)

• Rescue medication use

  At 24 hours

• 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)

  At 24 hours

• Perceived comfort as assessed by caregivers and bedside nurses questionnaire

  At 24 hours

• Delirium-related distress in caregivers and nurses assessed using Delirium Experience Questionnaire

  At 24 hours

• Proxy comfort goal level

  Up to 24 hours

Study Arms (4)

Group I (haloperidol, placebo)

EXPERIMENTAL

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.

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

Group II (lorazepam, placebo)

EXPERIMENTAL

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.

Drug: Lorazepam; Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Group III (haloperidol, lorazepam)

EXPERIMENTAL

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.

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

Group IV (placebo, lorazepam)

EXPERIMENTAL

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.

Drug: Lorazepam; Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Questionnaire Administration OTHER

Ancillary studies

Group I (haloperidol, placebo); Group II (lorazepam, placebo); Group III (haloperidol, lorazepam); Group IV (placebo, lorazepam)

Haloperidol DRUG

Given IV

Also known as: Haldol, McN-JR-1625, R 1625, R-1625

Group I (haloperidol, placebo); Group III (haloperidol, lorazepam)

Lorazepam DRUG

Given IV

Also known as: Ativan

Group II (lorazepam, placebo); Group III (haloperidol, lorazepam); Group IV (placebo, lorazepam)

Placebo OTHER

Given IV

Also known as: placebo therapy, PLCB, sham therapy

Group I (haloperidol, placebo); Group II (lorazepam, placebo); Group IV (placebo, lorazepam)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Group I (haloperidol, placebo); Group II (lorazepam, placebo); Group III (haloperidol, lorazepam); Group IV (placebo, lorazepam)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \[Patients\] 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-5 criteria
• \[Patients\] Hyperactive or mixed delirium with RASS ≥1\* in the past 24 h despite efforts to treat potential underlying causes
• \[Patients\] 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
• \[Patients\] Age 18 years or older
• \[Caregivers\] Patient's spouse, adult child, sibling, parent, other relative, or significant other (partner as defined by patient)
• \[Caregivers\] Age 18 years or older

You may not qualify if:

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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Hosptial de Cancer de Barretos

Barretos, São Paulo, 14784, Brazil

Location

Related Publications (1)

• 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.

  PMID: 40742738 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Delirium; Neoplasm Metastasis; Recurrence

Interventions

Haloperidol; Lorazepam

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Neoplastic Processes; Neoplasms; Pathologic Processes; Disease Attributes

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David Hui

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 16, 2018
• Study Start: July 17, 2019
• Primary Completion: February 28, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

BR (1); US (2)