Clinical trial NCT03021486: Haloperidol With or Without Chlorpromazine in Treating Delirium in Patients With Advanced, Metastatic, or Recurrent Cancer
Official title: Haloperidol and/or Chlorpromazine for Refractory Agitated Delirium in the Palliative Care Unit
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Advanced Malignant Neoplasm
Delirium
Locally Advanced Malignant Neoplasm
Metastatic Malignant Neoplasm
Recurrent Malignant Neoplasm
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institutes of Health (NIH)
name: National Institute of Nursing Research (NINR)
First posted: 2017-01-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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. Haloperidol and chlorpromazine may control the symptoms of delirium (loss of contact with reality) in patients with cancer.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Change in Richmond Agitation Sedation Score (RASS) (0-24h)
timeFrame: Time 0 or Baseline and 24 hours after study medication administration
Secondary outcomes:
measure: Percentage of Participants With RASS Score -2 to 0
timeFrame: Time 0 or Baseline and 24 hours later.
measure: Change in RASS Score (0-30 Minutes)
timeFrame: Time 0 or Baseline and 30 minutes later.
measure: Number of Participants With RASS Score of >=1
timeFrame: 0 or Baseline and 24 hours later
measure: Pattern of Medication Use
timeFrame: Baseline and 24 hours
measure: Perceived Comfort Level as Assessed by Caregiver
timeFrame: Baseline and 24 hour
measure: Perceived Comfort Level as Assessed by Nurse
timeFrame: Baseline and 24 hour
measure: Change in Delirium Experience Questionnaire
timeFrame: Baseline and Day 3
measure: Memorial Delirium Assessment Scale (MDAS)
timeFrame: Baseline and 24 hours
measure: Edmonton Expression Assessment System, ESAS
timeFrame: Baseline and 24 hours
measure: Udvalg for Kliniske Undersogelser, UKU
timeFrame: Baseline and 3 days
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Hui
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.