Haloperidol and/or Chlorpromazine for Refractory Agitated Delirium

Study Groups:

If you are found to be eligible and agree to take part, you will be randomly assigned (as in
a roll of the dice) to 1 of 3 study groups. This is done because no one knows if one study
group is better, the same, or worse than the other group. You will have an equal chance of
being in each group.

- If you are in Group 1, you will receive haloperidol.

- If you are in Group 2, you will receive chlorpromazine.

- If you are in Group 3, you will receive haloperidol and chlorpromazine.

Neither you nor the study staff will know which study drug you are receiving. However, if
needed for your safety, the study staff will be able to find out what you are receiving.

Study Drug Administration:

You will receive the study drug(s) by vein over about 3-15 minutes every 4 hours until you
are discharged from the palliative care unit or you withdraw from the study. You may receive
additional doses every 1 hour, if needed. The dose level and length of administration may be
raised or lowered to meet your needs.

Length of Treatment:

You may continue receiving the study drug(s) for as long as you are in the palliative care
unit. You may stop receiving the study drug(s) at any time that you and/or your caregiver
decides it is in your best interest.

Baseline Procedures:

Before your first dose of the study drug(s):

- Your demographic information (such as age, sex, date of birth, race, marital status, and
education), medical information, and cancer history will be recorded.

- You will complete a test to measure your level of delirium. To complete this test, the
study doctor will ask you to complete several thinking tasks, such as recalling a set of
numbers or words, remembering different objects, and stating what day it is. This test
should take less than 10 minutes to complete.

- You will complete 1 questionnaire about any symptoms you may be having. This should take
about 5 minutes to complete.

Study Procedures:

Every 8 hours during the first 24 hours that you are in the palliative care unit, you will
repeat the symptoms questionnaire. After the first 24 hours, you will complete the
questionnaire 1 time each day until you are discharged.

If and when you recover from the delirium, you will be asked to complete a questionnaire
about your experience with delirium. This should take about 5 minutes to complete. Your
active participation on this study will be over at that point.

Inclusion Criteria:

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 ( 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

9. [Family Caregivers] At the patient's bedside at least 4 h/day

Exclusion Criteria:

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)

5. [Patients] History of hypersensitivity to haloperidol or chlorpromazine

6. [Patients] On scheduled chlorpromazine within the past 48 h