Haloperidol With or Without Chlorpromazine in Treating Delirium in Patients With Advanced, Metastatic, or Recurrent Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- 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:
-
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.
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Obtain preliminary estimates of the between-arm effect size among haloperidol dose escalation, rotation to chlorpromazine, and combination therapy in the first 24 hours.
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group I (haloperidol) Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity. |
Drug: Haloperidol
Given IV
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
| Experimental: Group II (chlorpromazine) Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity. |
Drug: Chlorpromazine
Given IV
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
| Experimental: Group III (haloperidol, chlorpromazine) Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity. |
Drug: Chlorpromazine
Given IV
Other Names:
Drug: Haloperidol
Given IV
Other Names:
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- Richmond Agitation Sedation Scale (RASS) [24 hours after study medication administration]
A validated 10-point numeric rating scale that ranges from -5 (unarousable) to +4 (very agitated), where 0 denotes a calm and alert patient.
Secondary Outcome Measures
- Edmonton Symptom Assessment Scale (ESAS) [Daily during admission]
A 10-item symptom battery validated for assessing symptom burden over the previous 24 hours . Specifically, it assesses pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, sleep, and well-being using a numeric rating scale from 0 (best) to 10 (worst).
- Delirium Rating Scale (DRS) [Baseline]
A 16-item scale that has been validated for assessing delirium over the previous 24 hours. Each item is assigned a score between 0 (normal) and 3 (worst) that contributes to a severity score (13 items, total 39 points) and total score (maximum, 46 points). A total score of 18 or more suggests delirium.
- Memorial Delirium Assessment Scale (MDAS) [Baseline, every 8 hours on day 1, and daily during admission from Day 2]
A 10-item clinician-rated assessment scale that is validated for assessing delirium in cancer patients. It evaluates levels of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity, and sleep, assigning a score from 0 to 3 (total score, 0-30). A score >13 suggests delirium.
- Delirium Experience Questionnaire (DEQ) [Daily during admission]
Our research staff will interview family caregivers and nurses separately to record the recalled frequency of delirium symptoms and associated distress, similar to the procedure used in a previous study. These include disorientation to time and place, visual/tactile/auditory hallucinations, delusional thoughts, and psychomotor agitation, with symptom frequency and distress each rated on a scale from 0 to 4, where 0=no distress and 4=extremely distressed.
- Perceived Comfort and agitation [Daily during admission]
To examine whether study medications impact as perceived by blinded caregivers and bedside nurses, we will be asking them to rate the patient's perceived patient comfort level on a 0-10 point numeric rating scale, where 0=not at all and 10=very much, on a daily basis. We will also assess the overall impression of change by asking the caregiver "In my opinion, the patient was more comfortable after the study medication." for the first 3 days after study medication administration. Similarly, we will assess the average level of agitation over the past 24 hours on a 0-10 point numeric rating scale, where 0=not at all and 10=very much, on a daily basis. We will also assess the overall impression of change by asking the caregiver "In my opinion, the patient was less restless/agitated after the study medication." for the first 3 days after study medication administration.
- Adverse Events [Daily during admission]
Adverse effects related to the use of neuroleptics will be documented using NCI CTCAE v4.03; this will be supplemented by the UKU assessment, which is a validated questionnaire for documenting the adverse effects of neuroleptics. Vital signs will be assessed q8h during the first day of study medications and q12h thereafter. Discharge outcomes and survival will be assessed at the end of the study.
- Proxy sedation goals [Baseline and Day 1]
We will assess proxy sedation goals from the perspective of the bedside nurses and caregivers. It begins with three brief vignettes, describing 3 different hypothetical patients (agitation delirium, mixed delirium, hypoactive delirium) and asking about the sedation goal. Bedside nurses and caregivers will then answer five items that assess sedation level goals specific to the enrolled patient. The research staff will also complete the 5-question Communication Capacity Scale.
- After Death questionnaire [30-180 days after death]
This is an instrument to examine the quality of death. The questionnaire consists of 5 items to bereaved caregivers once over the telephone between 30-180 days after death in APCU. It contains one question based on the CanCORS study published by Wright et al. JAMA 2016 ("Overall, how would you rate the care received at the palliative care unit? Would you say it was excellent, very good, good, fair or poor?" We will define high quality end-of-life care as that which family member rated as excellent.)
Eligibility Criteria
Criteria
Inclusion:
-
[Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
-
[Patients] Admitted to the acute palliative care unit
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[Patients] Delirium as per DSM-V criteria (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5))
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[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).
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[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
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[Patients] Age 18 years or older
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[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
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[Patients] History of prolonged QTc interval (>500 ms) if documented by ECG within the past month
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[Patients] History of hypersensitivity to haloperidol or chlorpromazine
-
[Patients] On scheduled chlorpromazine within the past 48 h
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
- National Institutes of Health (NIH)
- National Institute of Nursing Research (NINR)
Investigators
- Principal Investigator: David Hui, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2016-0687
- NCI-2017-01065
- 2016-0687
- R21NR016736