Haloperidol + Lorazepam for Cancer-related Delirium

Not currently recruiting at 2 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: M.D. Anderson Cancer Center
Must be taking: Haloperidol
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well two medications, haloperidol and lorazepam, manage symptoms of agitated delirium in cancer patients receiving palliative care. The researchers aim to determine if these treatments can ease the distress caused by delirium, benefiting both patients and their caregivers. Participants will receive either haloperidol, lorazepam, a combination of the two, or a placebo for comparison. This trial suits those with advanced cancer experiencing persistent delirium that hasn't improved with usual treatments. As a Phase 2 and Phase 3 trial, this research evaluates the treatments' effectiveness in a larger group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in care.

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.

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

Research has shown that haloperidol and lorazepam can be well-tolerated in treating delirium in patients with advanced cancer. One study found that haloperidol is generally safe, though it may not always effectively treat delirium. Another study demonstrated that lorazepam significantly reduces agitation, making it a good option for calming symptoms.

When used together, haloperidol and lorazepam have shown promising results. A comprehensive analysis found that this combination had the highest success rate for treating delirium. Additionally, another study noted a significant decrease in agitated delirium when patients received both medications.

Overall, while some caution is advised, especially for older patients, both drugs have been shown to be safe when used correctly. This suggests that using both medications together could be a helpful option for managing delirium symptoms in cancer patients.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for cancer-related delirium because they involve two well-known medications, haloperidol and lorazepam, in novel combinations. Haloperidol is typically used to manage psychotic disorders, while lorazepam is commonly used for anxiety. In this trial, these medications are being administered intravenously and in combination, offering potentially faster relief for patients experiencing delirium. This approach could provide a more effective and rapid treatment option for managing delirium in palliative care settings compared to traditional methods, which often rely on singular treatments.

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

Research has shown that both haloperidol and lorazepam can ease symptoms of agitated delirium in cancer patients, particularly those in palliative care. In this trial, participants will join different treatment groups to evaluate these medications. Some will receive lorazepam, either alone or with haloperidol. Studies have found that this combination significantly reduces agitation more than haloperidol alone or a placebo. Reports indicate that using both haloperidol and lorazepam together greatly reduces symptoms, especially in the first 8 to 24 hours. Patients using these treatments have experienced a noticeable decrease in restlessness and agitation related to end-of-life delirium. These findings suggest that these medications can effectively manage symptoms and improve comfort for cancer patients dealing with delirium.34678

Who Is on the Research Team?

David Hui | MD Anderson Cancer Center

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 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.
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Exclusion Criteria

You have had a bad reaction to haloperidol or lorazepam in the past.
Your heart's electrical activity (measured by ECG) has shown a specific abnormality called prolonged QTc interval in the last month.
I have a history of myasthenia gravis or acute narrow angle glaucoma.
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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 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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Group IV (placebo, lorazepam)Experimental Treatment4 Interventions
Group II: Group III (haloperidol, lorazepam)Experimental Treatment4 Interventions
Group III: Group II (lorazepam, placebo)Experimental Treatment4 Interventions
Group IV: Group I (haloperidol, placebo)Experimental Treatment4 Interventions

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

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Approved in United States as Haldol for:
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Approved in European Union as Haldol for:
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Approved in Canada as Haldol for:
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Approved in Japan as Haldol for:

Find a Clinic Near You

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+

Published Research Related to This Trial

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.
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]
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.
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]

Citations

Frequency and Outcome of Neuroleptic Rotation in the ...Among 167 patients with delirium, 128 (77%) received only haloperidol and 39 (23%) received a second neuroleptic. Ninety-one patients (71%) who received ...
Haloperidol for the Treatment of Delirium in ICU PatientsWe obtained data on the primary outcome from 963 patients (96.3%) and data on 90-day mortality and the secondary outcomes from 987 patients (98.7%). At the ...
Review Haloperidol in palliative care: Indications and risksOverall, there is low-quality evidence to support that haloperidol may worsen symptoms of delirium in terminally ill patients with mild-moderate delirium, ...
ESMO 2024: Combination therapy reduced agitated ...Patients that received the combination of haloperidol and lorazepam experienced a significant decrease in agitated delirium when measured at 24 ...
Lorazepam, haloperidol significantly reduce end-of-life ...Key takeaways: Lorazepam and haloperidol can significantly decrease agitation related to end-of-life delirium for patients with cancer.
Haloperidol and Lorazepam for Delirium in Patients With ...Palliative therapy with haloperidol and lorazepam may reduce symptoms of delirium and help patients with advanced cancer live more comfortably. It is not yet ...
Prevalence of Delirium in Advance Cancer Patients ...In our study we found prevalence of delirium was 31.29% in advanced cancer patients admitted to hospice centre.
Efficacy and Safety of Haloperidol in the Prevention and ...The summary of results did not find that haloperidol is effective in preventing or treating delirium, though all included reviews found it a safe drug to use.
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