- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03021486
Haloperidol With or Without Chlorpromazine in Treating Delirium in Patients With Advanced, Metastatic, or Recurrent Cancer
Haloperidol and/or Chlorpromazine for Refractory Agitated Delirium in the Palliative Care Unit
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion:
- [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
Exclusion:
- [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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group I (haloperidol)
Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
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Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
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Experimental: Group II (chlorpromazine)
Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
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Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
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Experimental: Group III (haloperidol, chlorpromazine)
Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Richmond Agitation Sedation Score (RASS) (0-24h)
Time Frame: Time 0 or Baseline and 24 hours after study medication administration
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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.
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Time 0 or Baseline and 24 hours after study medication administration
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With RASS Score -2 to 0
Time Frame: Time 0 or Baseline and 24 hours later.
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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.
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Time 0 or Baseline and 24 hours later.
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Change in RASS Score (0-30 Minutes)
Time Frame: Time 0 or Baseline and 30 minutes later.
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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.
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Time 0 or Baseline and 30 minutes later.
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Number of Participants With RASS Score of >=1
Time Frame: 0 or Baseline and 24 hours later
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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.
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0 or Baseline and 24 hours later
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Pattern of Medication Use
Time Frame: Baseline and 24 hours
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Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.
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Baseline and 24 hours
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Perceived Comfort Level as Assessed by Caregiver
Time Frame: Baseline and 24 hour
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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).
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Baseline and 24 hour
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Perceived Comfort Level as Assessed by Nurse
Time Frame: Baseline and 24 hour
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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).
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Baseline and 24 hour
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Change in Delirium Experience Questionnaire
Time Frame: Baseline and Day 3
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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.
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Baseline and Day 3
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Memorial Delirium Assessment Scale (MDAS)
Time Frame: Baseline and 24 hours
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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.
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Baseline and 24 hours
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Edmonton Expression Assessment System, ESAS
Time Frame: Baseline and 24 hours
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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.
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Baseline and 24 hours
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Udvalg for Kliniske Undersogelser, UKU
Time Frame: Baseline and 3 days
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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.
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Baseline and 3 days
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David Hui, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Confusion
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Disease Attributes
- Neoplasms
- Delirium
- Recurrence
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Dopamine Agents
- Dopamine Antagonists
- Anti-Dyskinesia Agents
- Haloperidol
- Haloperidol decanoate
- Chlorpromazine
Other Study ID Numbers
- 2016-0687 (Other Identifier: M D Anderson Cancer Center)
- NCI-2017-01065 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- R21NR016736 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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