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

Phase 2

Active, not recruiting

Conditions: Delirium
Locally Advanced Malignant Neoplasm
Metastatic Malignant Neoplasm
Recurrent Malignant Neoplasm
Advanced Malignant Neoplasm

Interventions: Drug: Haloperidol
Drug: Chlorpromazine
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Registration Number: NCT03021486

Lead Sponsor: M.D. Anderson Cancer Center

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (haloperidol)	Quality-of-Life Assessment	Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group II (chlorpromazine)	Questionnaire Administration	Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group III (haloperidol, chlorpromazine)	Quality-of-Life Assessment	Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group II (chlorpromazine)	Quality-of-Life Assessment	Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group I (haloperidol)	Questionnaire Administration	Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group III (haloperidol, chlorpromazine)	Questionnaire Administration	Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group I (haloperidol)	Haloperidol	Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group II (chlorpromazine)	Chlorpromazine	Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group III (haloperidol, chlorpromazine)	Haloperidol	Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.
Group III (haloperidol, chlorpromazine)	Chlorpromazine	Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Change in Richmond Agitation Sedation Score (RASS) (0-24h)	Time 0 or Baseline and 24 hours after study medication administration	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.

Secondary Outcome Measures

Name	Time	Method
Change in RASS Score (0-30 Minutes)	Time 0 or Baseline and 30 minutes later.	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.
Percentage of Participants With RASS Score -2 to 0	Time 0 or Baseline and 24 hours later.	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.
Change in Delirium Experience Questionnaire	Baseline and Day 3	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.
Memorial Delirium Assessment Scale (MDAS)	Baseline and 24 hours	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.
Edmonton Expression Assessment System, ESAS	Baseline and 24 hours	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.
Udvalg for Kliniske Undersogelser, UKU	Baseline and 3 days	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.
Number of Participants With RASS Score of >=1	0 or Baseline and 24 hours later	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.
Pattern of Medication Use	Baseline and 24 hours	Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.
Perceived Comfort Level as Assessed by Nurse	Baseline and 24 hour	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).
Perceived Comfort Level as Assessed by Caregiver	Baseline and 24 hour	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).