Haloperidol +/- Chlorpromazine for Delirium in Cancer Patients

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: M.D. Anderson Cancer Center

Must be taking: Haloperidol

Must not be taking: Chlorpromazine

Disqualifiers: Myasthenia gravis, Glaucoma, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether haloperidol alone or with chlorpromazine can control delirium symptoms in cancer patients whose disease has spread or returned. Delirium can cause confusion and loss of contact with reality, which these medications aim to manage. The study includes three groups: one receiving haloperidol, another chlorpromazine, and the third a combination of both. It seeks patients with advanced cancer experiencing restlessness or agitation, who are already receiving haloperidol for delirium. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken chlorpromazine in the past 48 hours.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both haloperidol and chlorpromazine have been studied for their safety in treating delirium. Haloperidol carries a low risk of causing serious health problems. One study found that patients taking haloperidol were less likely to fall or get out of bed compared to those taking a placebo, indicating it is well-tolerated. Chlorpromazine has effectively improved delirium symptoms for many patients, with 80% showing lasting improvement in some cases. However, higher doses of antipsychotics like chlorpromazine can increase risks for terminally ill patients.

For those considering using both haloperidol and chlorpromazine together, about 30% of doctors often use this combination to manage delirium. Patients in palliative care may be more sensitive to side effects due to their health condition. Overall, haloperidol and chlorpromazine appear safe to use, but individual reactions can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore different ways to manage delirium in cancer patients using haloperidol and chlorpromazine. Unlike typical treatments that often focus solely on one drug, this investigation looks at both haloperidol and chlorpromazine separately and in combination, which could offer more flexible treatment options. Haloperidol and chlorpromazine work by blocking dopamine receptors, but using them together might enhance their effects or reduce side effects, offering a potentially more effective and tolerable solution. This approach could lead to more personalized care for patients, improving their quality of life during treatment.

What evidence suggests that this trial's treatments could be effective for delirium in cancer patients?

Research has shown that haloperidol, which participants in this trial may receive, can help reduce some symptoms of delirium, such as the need for extra medication and events related to agitation, although it doesn't significantly lessen delirium itself. Another treatment option in this trial is chlorpromazine, which studies indicate can greatly improve delirium symptoms in 80% of patients, especially in palliative care settings. Participants in this trial may also receive a combination of haloperidol and chlorpromazine, which significantly improved delirium symptoms in cancer patients. Both medications have effectively managed agitation and confusion in delirium. Therefore, promising evidence supports their use for treating delirium in cancer patients. ^{1 2 6 7 8}

Who Is on the Research Team?

David Hui

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced cancer experiencing delirium, who are admitted to the acute palliative care unit. They must have a diagnosis of hyperactive or mixed delirium and be on haloperidol treatment. Excluded are those with neuroleptic malignant syndrome, seizure disorders, Parkinson's disease, Alzheimer's dementia, hypersensitivity to the drugs being tested, myasthenia gravis, glaucoma or a prolonged QTc interval.

Inclusion Criteria

I am currently admitted to a palliative care unit.

My cancer is advanced and cannot be cured with surgery or radiation alone.

The patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)

Exclusion Criteria

You have had a bad reaction to haloperidol or chlorpromazine in the past.

I have had a seizure in the last week or a history of neuroleptic malignant syndrome.

I have taken chlorpromazine in the last 48 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive haloperidol and/or chlorpromazine intravenously every 4 hours to manage delirium symptoms

24 hours

Continuous monitoring in the acute palliative care unit

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 days

Daily assessments

What Are the Treatments Tested in This Trial?

Interventions

• Chlorpromazine
• Haloperidol

Trial Overview The study is testing whether adding chlorpromazine to haloperidol is more effective in treating delirium symptoms in patients with advanced cancer than using haloperidol alone. It's a randomized trial where patients will either receive both medications or just haloperidol while their quality of life and symptom changes are monitored.

How Is the Trial Designed?

Group I: Group III (haloperidol, chlorpromazine) Experimental Treatment 4 Interventions

Patients receive haloperidol and chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Group II: Group II (chlorpromazine) Experimental Treatment 3 Interventions

Patients receive chlorpromazine IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Group III: Group I (haloperidol) Experimental Treatment 3 Interventions

Patients receive haloperidol IV over 3-15 minutes every 4 hours in the absence of unacceptable toxicity.

Haloperidol is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Haldol for:

• Schizophrenia
• Acute psychosis
• Agitation
• Delirium

Approved in European Union as Haldol for:

• Schizophrenia
• Acute psychosis
• Agitation
• Delirium
• Tourette's syndrome

Approved in Canada as Haldol for:

• Schizophrenia
• Acute psychosis
• Agitation
• Delirium

Approved in Japan as Haldol for:

• Schizophrenia
• Acute psychosis
• Agitation
• Delirium

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Institute of Nursing Research (NINR)

Collaborator

Trials

623

Recruited

10,400,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11170992/

Pharmacologic Management of End-of-Life Delirium The Chlorpromazine and Haloperidol for Agitated Delirium (CHAD) study is a single-center, double-blind, double-dummy randomized clinical trial ...

2. liebertpub.com liebertpub.com/doi/10.1089/jpm.2022.0308

Chlorpromazine's Potential Role in Palliating Distressing ... Results: Sustained improvement in symptoms of delirium was seen in 80% of patients as identified in the palliative psychiatrist's progress notes. Meanwhile, 75% ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8274723/

Multifaceted effect of chlorpromazine in cancer Subsequent studies showed that CPZ can calm severely agitated psychotic patients, paving the way for its use as an antipsychotic medication worldwide [13].

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0016508555800844

Anti-Emetic Effect of Chlorpromazine (Thorazine) in Cancer ... The drug was found to be effective, greatly surpassing the effectiveness of placebos, in combating the nausea and vomiting due to uremia and radiation therapy.

5. journals.sagepub.com journals.sagepub.com/doi/full/10.1089/jpm.2022.0308

Chlorpromazine's Potential Role in Palliating Distressing ... Improvement in delirium was also measured as a reduction in the mean daily DOSS scores from baseline (day before CPZ initiation) to a value <3. A patient was ...

6. liebertpub.com liebertpub.com/doi/full/10.1089/jpm.2022.0308

Chlorpromazine's Potential Role in Palliating Distressing ... Results: Sustained improvement in symptoms of delirium was seen in 80% of patients as identified in the palliative psychiatrist's progress notes. Meanwhile, 75 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0885392422004730

Association of Antipsychotic Dose With Survival ... Higher doses of antipsychotics were associated with increased mortality in terminally ill cancer patients with delirium.

8. jpsmjournal.com jpsmjournal.com/article/S0885-3924(22)00786-2/fulltext

Drug Choice for Hyperactive Delirium in Terminally-Ill ... However, there is disagreement regarding the effectiveness and safety of pharmacological treatment for delirium. Pharmacological treatment may ...