Haloperidol + Lorazepam for Cancer-related Delirium

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: M.D. Anderson Cancer Center

Must be taking: Haloperidol

Must not be taking: Lorazepam

Disqualifiers: Myasthenia gravis, Seizure disorder, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 hours

110 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing how well haloperidol and lorazepam help manage severe agitation and confusion in cancer patients receiving palliative care. These patients often do not respond to usual treatments. Haloperidol and lorazepam work by calming the brain and reducing symptoms of agitation and confusion.

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 been on scheduled lorazepam in the past 48 hours.

What evidence supports the effectiveness of the drug combination of haloperidol and lorazepam for treating cancer-related delirium?

Research shows that the combination of haloperidol and lorazepam has been used effectively to quickly and safely calm delirium symptoms in over 2,000 cancer patients, even in emergency situations. This combination allows for lower doses of haloperidol, making it a preferred choice for managing delirium in critically ill patients. ^{1 2 3 4 5}

Is the combination of haloperidol and lorazepam safe for treating delirium in cancer patients?

Research shows that the combination of haloperidol and lorazepam has been used safely in over 2,000 cancer patients with delirium, even in those with severe illness. Side effects are generally mild and well tolerated, making it a safe option for managing symptoms in these patients. ^{1 2 3 6 7}

What makes the drug combination of Haloperidol and Lorazepam unique for treating cancer-related delirium?

The combination of Haloperidol and Lorazepam for cancer-related delirium is unique because it uses two different types of medications: Haloperidol, an antipsychotic that helps manage confusion and agitation, and Lorazepam, a sedative that can reduce anxiety and help with sleep. This dual approach may offer a more comprehensive management of symptoms compared to using a single medication. ^{8 9 10 11 12}

Research Team

David Hui

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced cancer experiencing persistent agitated delirium, despite treatment efforts. They must be admitted to a palliative care unit and have been on haloperidol or required it for agitation. Excluded are those with certain neurological disorders, history of severe reactions to the drugs being tested, or specific heart rhythm abnormalities.

Inclusion Criteria

I have taken up to 8 mg of haloperidol for delirium or needed at least 4 mg for agitation recently.

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

I am currently in a hospital's palliative care unit.

Exclusion Criteria

Your heart's electrical activity (measured by ECG) has shown a specific abnormality called prolonged QTc interval in the last month.

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

I have a history of myasthenia gravis or acute narrow angle glaucoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive haloperidol and/or lorazepam intravenously every 4 hours and then every hour as needed until discharge from the palliative care unit

Up to 24 hours

Continuous monitoring in palliative care unit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Phone follow-up with caregivers

Treatment Details

Interventions

• Haloperidol
• Lorazepam

Trial Overview The study examines if haloperidol and lorazepam can effectively manage symptoms of agitated delirium in patients undergoing palliative care for advanced cancer. It also looks at how these medications might affect the well-being of caregivers.

Participant Groups

Group I: Group IV (placebo, lorazepam) Experimental Treatment 4 Interventions

Patients receive two different placebos IV every 4 hours. Patients then receive placebo IV and lorazepam IV over 3-15 minutes every hour as needed until discharge from palliative care unit.

Group II: Group III (haloperidol, lorazepam) Experimental Treatment 4 Interventions

Patients receive haloperidol IV over 3-15 minutes every 4 hours and then every hour as needed and lorazepam IV over 3-15 minutes every 4 hours and then every hour as needed until discharge from palliative care unit.

Group III: Group II (lorazepam, placebo) Experimental Treatment 4 Interventions

Patients receive lorazepam IV over 3-15 minutes every 4 hours and then every hour as needed and placebo IV every 4 hours and then every hour as needed until discharge from palliative care unit.

Group IV: Group I (haloperidol, placebo) Experimental Treatment 4 Interventions

Patients receive haloperidol IV over 3-15 minutes every 4 hours and then every hour as needed and placebo IV every 4 hours and then every hour as needed until discharge from palliative care unit.

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 Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 30 adult AIDS patients with delirium, treatment with low doses of haloperidol or chlorpromazine significantly improved delirium symptoms, while lorazepam showed no improvement and caused adverse effects.

Haloperidol and chlorpromazine were associated with a low prevalence of extrapyramidal side effects, making them safer options for treating delirium in this patient population compared to lorazepam, which was terminated early due to treatment-limiting side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Breitbart, W., Marotta, R., Platt, MM., et al.[2022]

In a study of 61 acute schizophrenic patients over 28 days, combining lorazepam with haloperidol did not lead to better outcomes in reducing psychotic symptoms compared to haloperidol alone, as measured by BPRS scores.

The study found no significant relationship between lorazepam serum levels and improvements in psychotic symptoms or side effects, suggesting that the risks of using lorazepam alongside haloperidol may not be justified by any potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis. Stevens, A., Stevens, I., Mahal, A., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Emergency intravenous sedation of the delirious, medically ill patient. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

Usage of haloperidol for delirium in cancer patients. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of delirium in the critically ill patient. [2008]

5. Germany pubmed.ncbi.nlm.nih.gov

Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis. [2013]

6. Australia pubmed.ncbi.nlm.nih.gov

Lorazepam as an adjunct to antiemetic therapy with haloperidol in patients receiving cytotoxic chemotherapy. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of levetiracetam in patients with glioma: a clinical prospective study. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Associations of levetiracetam use with the safety and tolerability profile of chemoradiotherapy for patients with newly diagnosed glioblastoma. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Risk of Glioblastoma Multiforme in Patients Taking Ion Channel Blockers. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Levetiracetam as a sensitizer of concurrent chemoradiotherapy in newly diagnosed glioblastoma: An open-label phase 2 study. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of the effects of valproic acid and levetiracetam on apoptosis in the human ovarian cancer cell line OVCAR-3. [2020]