Advanced Malignant Neoplasm, Delirium, Locally Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm
Conditions
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.
Interventions
DRUGChlorpromazine
Given IV
DRUGHaloperidol
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
National Institutes of Health (NIH)
National Institute of Nursing Research (NINR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 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). |
| 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). |
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid Hui
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Adult participants (age\>18) with an active diagnosis of cancer were recruited between palliative and supportive Care unit at MD Anderson Cancer Center who met the inclusion and exclusion criteria.
Pre-assignment details
A total of 70 participants were consented, 2 were inevaluable and 68 were randomly assigned for interventions.
Participants by arm
| Arm | Count |
|---|---|
| Escalation Group Participants receive 2 mg of haloperidol IV over 3-15 minutes every 4 hours in absence of unacceptable toxicity. | 15 |
| Rotation Group Participants receive 25 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity. | 16 |
| Combination Group Participants receive 1 mg of haloperidol and 12.5 mg of chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity. | 14 |
| Total | 45 |
Baseline characteristics
| Characteristic | Combination Group | Total | Escalation Group | Rotation Group |
|---|---|---|---|---|
| Age, Continuous | 60 years | 64 years | 65 years | 63 years |
| Cancer Type Breast | 1 Participants | 5 Participants | 3 Participants | 1 Participants |
| Cancer Type Gastrointestinal | 2 Participants | 14 Participants | 5 Participants | 7 Participants |
| Cancer Type Genitourinary | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Cancer Type Gynecological | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Cancer Type Hematological | 2 Participants | 5 Participants | 0 Participants | 3 Participants |
| Cancer Type Others | 3 Participants | 6 Participants | 2 Participants | 1 Participants |
| Cancer Type Respiratory | 3 Participants | 10 Participants | 4 Participants | 3 Participants |
| Education Advanced degree | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Education College | 2 Participants | 11 Participants | 4 Participants | 5 Participants |
| Education Completed High School | 4 Participants | 16 Participants | 5 Participants | 7 Participants |
| Education Some College | 3 Participants | 10 Participants | 4 Participants | 3 Participants |
| Education Some High school or less | 3 Participants | 4 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 41 Participants | 14 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Metastatic cancer or advanced stage disease | 14 Participants | 45 Participants | 15 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 37 Participants | 11 Participants | 14 Participants |
| Region of Enrollment United States | 14 participants | 45 participants | 15 participants | 16 participants |
| Sex: Female, Male Female | 8 Participants | 19 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 26 Participants | 10 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 15 | 16 / 16 | 14 / 14 |
| other Total, other adverse events | 6 / 15 | 5 / 16 | 3 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 | 0 / 14 |
Outcome results
Primary
Change in Richmond Agitation Sedation Score (RASS) (0-24h)
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.
Time frame: Time 0 or Baseline and 24 hours after study medication administration
Population: Analysis included 31 participants who completed 24 hours of the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escalation Group | Change in Richmond Agitation Sedation Score (RASS) (0-24h) | -3.6 score on a scale |
| Rotation Group | Change in Richmond Agitation Sedation Score (RASS) (0-24h) | -3.3 score on a scale |
| Combination Group | Change in Richmond Agitation Sedation Score (RASS) (0-24h) | -3.0 score on a scale |
p-value: 0.71Wilcoxon Rank Sum Test
Secondary
Change in Delirium Experience Questionnaire
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.
Time frame: Baseline and Day 3
Population: Analysis included 37 participants who completed this questionnaire at that time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, tactile hallucination - distress | -0.5 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, delusional thoughts - frequency | -0.8 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, visual hallucination - frequency | -1 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, visual hallucination - distress | -0.6 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, psychomotor agitation- frequency | -1.2 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to place - frequency | -0.9 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to place - distress | -0.3 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to time - distress | -0.3 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, auditory hallucination - distress | -0.3 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, tactile hallucination - frequency | -0.4 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, psychomotor agitation - distress | -0.8 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to time - frequency | -0.8 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, auditory hallucination - frequency | -0.1 score on a scale |
| Escalation Group | Change in Delirium Experience Questionnaire | Nursing assessment, delusional thoughts - distress | -0.6 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, tactile hallucination - distress | 0 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to time - frequency | -0.8 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to place - frequency | -0.8 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, visual hallucination - frequency | 0 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, tactile hallucination - frequency | 0.1 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, auditory hallucination - frequency | 0.1 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, delusional thoughts - frequency | 0 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, psychomotor agitation- frequency | -0.8 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to time - distress | -0.3 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to place - distress | -0.3 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, visual hallucination - distress | 0.1 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, auditory hallucination - distress | 0 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, delusional thoughts - distress | 0 score on a scale |
| Rotation Group | Change in Delirium Experience Questionnaire | Nursing assessment, psychomotor agitation - distress | -0.5 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, delusional thoughts - distress | -0.1 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, visual hallucination - distress | -0.4 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, auditory hallucination - frequency | -0.4 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, tactile hallucination - frequency | -0.9 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, tactile hallucination - distress | -0.5 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, visual hallucination - frequency | -0.7 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to time - frequency | 0.2 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, auditory hallucination - distress | -0.2 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to place - frequency | 0.3 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to time - distress | -0.5 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, psychomotor agitation- frequency | -0.4 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, psychomotor agitation - distress | -0.8 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, disorientation to place - distress | -0.4 score on a scale |
| Combination Group | Change in Delirium Experience Questionnaire | Nursing assessment, delusional thoughts - frequency | 0.2 score on a scale |
Comparison: Nursing assessment, disorientation to time - frequencyp-value: 0.12Wilcoxon Rank Sum Test
Comparison: Nursing assessment, disorientation to place - frequencyp-value: 0.07Wilcoxon Rank Sum Test
Comparison: Nursing assessment, visual hallucination - frequencyp-value: 0.051Wilcoxon Rank Sum Test
Comparison: Nursing assessment, tactile hallucination - frequencyp-value: 0.048Wilcoxon Rank Sum Test
Comparison: Nursing assessment, auditory hallucination - frequencyp-value: 0.15Wilcoxon Rank Sum Test
Comparison: Nursing assessment, delusional thoughts - frequencyp-value: 0.1Wilcoxon Rank Sum Test
Comparison: Nursing assessment, psychomotor agitation- frequencyp-value: 0.15Wilcoxon Rank Sum Test
Comparison: Nursing assessment, disorientation to time - distressp-value: 0.98Wilcoxon Rank Sum Test
Comparison: Nursing assessment, disorientation to place - distressp-value: 0.93Wilcoxon Rank Sum Test
Comparison: Nursing assessment, visual hallucination - distressp-value: 0.08Wilcoxon Rank Sum Test
Comparison: Nursing assessment, tactile hallucination - distressp-value: 0.28Wilcoxon Rank Sum Test
Comparison: Nursing assessment, auditory hallucination - distressp-value: 0.83Wilcoxon Rank Sum Test
Comparison: Nursing assessment, delusional thoughts - distressp-value: 0.22Wilcoxon Rank Sum Test
Comparison: Nursing assessment, psychomotor agitation - distressp-value: 0.75Wilcoxon Rank Sum Test
Secondary
Change in RASS Score (0-30 Minutes)
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.
Time frame: Time 0 or Baseline and 30 minutes later.
Population: Analysis included 45 participants who completed first 30 minutes of study
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escalation Group | Change in RASS Score (0-30 Minutes) | -2.6 score on a scale |
| Rotation Group | Change in RASS Score (0-30 Minutes) | -2.4 score on a scale |
| Combination Group | Change in RASS Score (0-30 Minutes) | -2.1 score on a scale |
p-value: 0.86Wilcoxon Rank Sum Test
Secondary
Edmonton Expression Assessment System, ESAS
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.
Time frame: Baseline and 24 hours
Population: Analysis included 33 participants who completed this questionnaire at that time point. Note that 9 participants completed 'feeling of well being' question for Combination group, and 13 participants completed 'pain' and 'sleep' questions for Escalation group
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Escalation Group | Edmonton Expression Assessment System, ESAS | Pain | -1.3 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Fatigue | -0.5 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Nausea | 0.1 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Depression | -1.4 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Anxiety | -1.5 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Drowsiness | -0.2 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Appetite | -0.3 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Feeling of well being* | 0.2 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Shortness of breath | 0.8 score on a scale |
| Escalation Group | Edmonton Expression Assessment System, ESAS | Sleep | -2.7 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Shortness of breath | -2.2 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Pain | -4.1 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Drowsiness | -0.6 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Anxiety | -4.8 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Fatigue | -3 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Sleep | -5.1 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Feeling of well being* | -1.6 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Nausea | -1.8 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Appetite | -0.6 score on a scale |
| Rotation Group | Edmonton Expression Assessment System, ESAS | Depression | -1.2 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Feeling of well being* | 0 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Depression | -0.8 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Anxiety | -0.9 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Drowsiness | 0.7 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Shortness of breath | 0 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Appetite | 0.1 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Pain | -1.1 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Sleep | -2.7 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Fatigue | 1 score on a scale |
| Combination Group | Edmonton Expression Assessment System, ESAS | Nausea | -0.4 score on a scale |
Comparison: Mean change in pain.p-value: 0.02Wilcoxon Rank Sum Test
Comparison: Mean change in Fatigue.p-value: 0.1Wilcoxon Rank Sum Test
Comparison: Mean change in Nausea.p-value: 0.02Wilcoxon Rank Sum Test
Comparison: Mean change in Depression.p-value: 0.97Wilcoxon Rank Sum Test
Comparison: Mean change in Anxiety.p-value: 0.03Wilcoxon Rank Sum Test
Comparison: Mean change in Drowsiness.p-value: 0.68Wilcoxon Rank Sum Test
Comparison: Mean change in Appetite.p-value: 0.8Wilcoxon Rank Sum Test
Comparison: Mean change in Feeling of well being.p-value: 0.45Wilcoxon Rank Sum Test
Comparison: Mean change in Shortness of breath.p-value: 0.16Wilcoxon Rank Sum Test
Comparison: Mean change in Sleep.p-value: 0.12Wilcoxon Rank Sum Test
Secondary
Memorial Delirium Assessment Scale (MDAS)
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.
Time frame: Baseline and 24 hours
Population: Analysis included 30 participants who completed this questionnaire at that time point
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Escalation Group | Memorial Delirium Assessment Scale (MDAS) | -2.7 score on a scale |
| Rotation Group | Memorial Delirium Assessment Scale (MDAS) | 1 score on a scale |
| Combination Group | Memorial Delirium Assessment Scale (MDAS) | 0.3 score on a scale |
p-value: 0.09Wilcoxon Rank Sum Test
Secondary
Number of Participants With RASS Score of >=1
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.
Time frame: 0 or Baseline and 24 hours later
Population: Analysis included 45 participants who completed first 24 hours of study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Escalation Group | Number of Participants With RASS Score of >=1 | 12 Participants |
| Rotation Group | Number of Participants With RASS Score of >=1 | 7 Participants |
| Combination Group | Number of Participants With RASS Score of >=1 | 9 Participants |
p-value: 0.12Two-tailed Fisher's exact test
Secondary
Pattern of Medication Use
Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record.
Time frame: Baseline and 24 hours
Population: Analysis included 45 participants who were still on study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Escalation Group | Pattern of Medication Use | Benzodiazepine use in first 24 hrs (as needed) | 0 Participants |
| Escalation Group | Pattern of Medication Use | Benzodiazepine use in first 24 hrs (scheduled) | 1 Participants |
| Escalation Group | Pattern of Medication Use | Need for study med dose escalation in first 24 hrs | 4 Participants |
| Rotation Group | Pattern of Medication Use | Benzodiazepine use in first 24 hrs (scheduled) | 0 Participants |
| Rotation Group | Pattern of Medication Use | Need for study med dose escalation in first 24 hrs | 1 Participants |
| Rotation Group | Pattern of Medication Use | Benzodiazepine use in first 24 hrs (as needed) | 0 Participants |
| Combination Group | Pattern of Medication Use | Need for study med dose escalation in first 24 hrs | 7 Participants |
| Combination Group | Pattern of Medication Use | Benzodiazepine use in first 24 hrs (as needed) | 4 Participants |
| Combination Group | Pattern of Medication Use | Benzodiazepine use in first 24 hrs (scheduled) | 0 Participants |
p-value: 0.007Two-tailed Fisher's exact test
Secondary
Perceived Comfort Level as Assessed by Caregiver
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).
Time frame: Baseline and 24 hour
Population: Analysis included 37 participants who completed this questionnaire at that time point
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Escalation Group | Perceived Comfort Level as Assessed by Caregiver | Perceived To Have A High Level of Comfort (More Comfortable) | 8 Participants |
| Escalation Group | Perceived Comfort Level as Assessed by Caregiver | Perceived To Have A Low Level of Agitation (Less Agitated) | 9 Participants |
| Rotation Group | Perceived Comfort Level as Assessed by Caregiver | Perceived To Have A High Level of Comfort (More Comfortable) | 10 Participants |
| Rotation Group | Perceived Comfort Level as Assessed by Caregiver | Perceived To Have A Low Level of Agitation (Less Agitated) | 10 Participants |
| Combination Group | Perceived Comfort Level as Assessed by Caregiver | Perceived To Have A High Level of Comfort (More Comfortable) | 6 Participants |
| Combination Group | Perceived Comfort Level as Assessed by Caregiver | Perceived To Have A Low Level of Agitation (Less Agitated) | 6 Participants |
Comparison: Perceived Comfort level as assessed by caregiverp-value: 0.83Two-tailed Fisher's exact test
Comparison: Perceived agitation level as assessed by caregiverp-value: 0.82Two-tailed Fisher's exact test
Secondary
Perceived Comfort Level as Assessed by Nurse
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).
Time frame: Baseline and 24 hour
Population: Analysis included 37 participants who completed this questionnaire at that time point
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Escalation Group | Perceived Comfort Level as Assessed by Nurse | Perceived To Have A High Level of Comfort (More Comfortable) | 9 Participants |
| Escalation Group | Perceived Comfort Level as Assessed by Nurse | Perceived To Have A Low Level of Agitation (Less Agitated) | 8 Participants |
| Rotation Group | Perceived Comfort Level as Assessed by Nurse | Perceived To Have A High Level of Comfort (More Comfortable) | 9 Participants |
| Rotation Group | Perceived Comfort Level as Assessed by Nurse | Perceived To Have A Low Level of Agitation (Less Agitated) | 8 Participants |
| Combination Group | Perceived Comfort Level as Assessed by Nurse | Perceived To Have A Low Level of Agitation (Less Agitated) | 7 Participants |
| Combination Group | Perceived Comfort Level as Assessed by Nurse | Perceived To Have A High Level of Comfort (More Comfortable) | 7 Participants |
Comparison: Perceived Comfort level as assessed by nursep-value: 0.82Two-tailed Fisher's exact test
Comparison: Perceived agitation level as assessed by nursep-value: 0.91Two-tailed Fisher's exact test
Secondary
Percentage of Participants With RASS Score -2 to 0
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.
Time frame: Time 0 or Baseline and 24 hours later.
Population: Analysis included 31 participants who completed 24 hours of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Escalation Group | Percentage of Participants With RASS Score -2 to 0 | 2 Participants |
| Rotation Group | Percentage of Participants With RASS Score -2 to 0 | 3 Participants |
| Combination Group | Percentage of Participants With RASS Score -2 to 0 | 5 Participants |
Secondary
Udvalg for Kliniske Undersogelser, UKU
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.
Time frame: Baseline and 3 days
Population: Analysis included 25 participants who were still on study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Escalation Group | Udvalg for Kliniske Undersogelser, UKU | Tremor (decreased) | 0 Participants |
| Escalation Group | Udvalg for Kliniske Undersogelser, UKU | Akathisia (decreased) | 0 Participants |
| Rotation Group | Udvalg for Kliniske Undersogelser, UKU | Tremor (decreased) | 0 Participants |
| Rotation Group | Udvalg for Kliniske Undersogelser, UKU | Akathisia (decreased) | 0 Participants |
| Combination Group | Udvalg for Kliniske Undersogelser, UKU | Tremor (decreased) | 1 Participants |
| Combination Group | Udvalg for Kliniske Undersogelser, UKU | Akathisia (decreased) | 1 Participants |