Haloperidol + Lorazepam for Delirium in Advanced Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Haloperidol

Must not be taking: Benzodiazepines, Chlorpromazine

Disqualifiers: Myasthenia gravis, Glaucoma, Parkinson's, 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: 8 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether haloperidol, a common medication for confusion, with or without lorazepam, can better ease symptoms of delirium in patients with advanced cancer. Delirium includes issues like confusion and memory problems, and the trial aims to determine if these medications can help patients feel more comfortable. Participants have advanced cancer that cannot be controlled and are experiencing delirium in a palliative care unit. Those dealing with confusion and memory issues related to their cancer may find this trial relevant. As a Phase 2 trial, the 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 requires that you have not taken regular doses of benzodiazepine or chlorpromazine in the past 48 hours. If you are on these medications, you may need to stop them before participating.

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

Research shows that using haloperidol and lorazepam together is generally safe for patients with advanced cancer. Studies have found that this combination can help reduce symptoms of agitated delirium, such as confusion and restlessness. Patients taking both medications often feel better within just a few hours.

Importantly, no major safety issues have been reported with this treatment combination in the available studies. The evidence suggests that adding lorazepam to haloperidol can effectively manage delirium symptoms without causing significant side effects. While every treatment can have side effects, the data supports the safety of using these drugs together for this condition. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for delirium in advanced cancer, which typically involves medications like haloperidol alone, this trial explores the combination of haloperidol with lorazepam. Researchers are excited about this approach because lorazepam, a benzodiazepine, may enhance the calming effects of haloperidol, potentially offering quicker relief from delirium symptoms. Additionally, this combination is administered intravenously, which could provide faster onset of action compared to oral medications. These features make the treatment potentially transformative for patients experiencing the distress of delirium in a palliative care setting.

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

In this trial, participants will receive either a combination of lorazepam and haloperidol or haloperidol with a placebo. Research has shown that lorazepam combined with haloperidol reduces agitation related to delirium more effectively than haloperidol alone. Lorazepam, whether used by itself or with haloperidol, significantly reduces agitation in patients with advanced cancer. One study found that adding lorazepam to haloperidol led to a greater decrease in agitation after 8 hours compared to using only haloperidol. This combination may better control delirium symptoms for those with ongoing issues. Overall, evidence supports that the combination of lorazepam and haloperidol manages agitation more effectively than haloperidol alone. ^{3 6 7 8 9}

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 in a palliative care unit and have had hyperactive or mixed symptoms recently. They must be on low-dose haloperidol and not have conditions like myasthenia gravis, glaucoma, Parkinson's disease, dementia, uncontrolled seizures, or certain heart issues.

Inclusion Criteria

I have a close family member or partner involved.

I have experienced severe confusion or agitation recently.

I have been diagnosed with delirium.

Exclusion Criteria

I am allergic to haloperidol or benzodiazepines.

I have taken benzodiazepine or chlorpromazine regularly in the last 48 hours.

My heart failure is not getting worse right now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either lorazepam or placebo with haloperidol to assess the effect on delirium over an 8-hour period

8 hours

Continuous monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 days

Daily assessments in the palliative care unit

What Are the Treatments Tested in This Trial?

Interventions

• Haloperidol
• Lorazepam

Trial Overview The study is testing if adding lorazepam to haloperidol can better reduce delirium symptoms in patients with advanced cancer compared to using just haloperidol. Participants will be randomly assigned to receive either both drugs or only haloperidol alongside a placebo.

How Is the Trial Designed?

Group I: Lorazepam + Haloperidol Experimental Treatment 3 Interventions

Participants given a single dose of lorazepam 3 mg by vein, in addition to a standardized dose of haloperidol 8 mg/day by vein, while in palliative care unit. Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete

Group II: Placebo + Haloperidol Active Control 3 Interventions

Participants receive placebo, preservative free 0.9% normal saline, by vein plus a standardized dose of haloperidol 8 mg/day by vein, while in palliative care unit. Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete

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+

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03060-6/fulltext

1476O Haloperidol and lorazepam for agitated delirium in ... Scheduled medications proactively reduced breakthrough agitation compared to placebo. Lorazepam and combination therapy were more effective than haloperidol.

2. mdanderson.org mdanderson.org/newsroom/research-newsroom/lorazepam-significantly-reduces-agitation-in-patients-with-advanced-cancer-and-delirium.h00-159778023.html

Lorazepam significantly reduces agitation in patients with ... Follow-up results show that lorazepam, alone or with haloperidol, significantly reduced agitation more than haloperidol alone or a placebo.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28975307/

Effect of Lorazepam With Haloperidol vs ... - PubMed The addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours.

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2654385

Effect of Lorazepam With Haloperidol vs ... The addition of lorazepam to haloperidol may provide superior control of agitation in patients with persistent delirium.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03743649

NCT03743649 | Haloperidol and Lorazepam in Controlling ... Haloperidol and lorazepam may help in controlling symptoms of agitated delirium in patients with cancer and may lessen any distress that their caregivers may ...

6. mdanderson.org mdanderson.org/newsroom/esmo--combination-therapy-reduced-agitated-delirium-in-patients-with-advanced-cancers.h00-159700701.html

Combination therapy reduced agitated delirium in patients ... Patients that received the combination of haloperidol and lorazepam experienced a significant decrease in agitated delirium when measured at 24 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5661867/

Effect of Lorazepam With Haloperidol vs ... Lorazepam + haloperidol was associated with a significantly greater reduction in RASS score than placebo + haloperidol at 8 hours.

8. aafp.org aafp.org/pubs/afp/issues/2018/0215/od4.html

Lorazepam Added to Haloperidol Effective for Agitated ... Using a single dose of lorazepam in combination with haloperidol decreases agitation in end-of-life patients with cancer who had persistent ...

9. mdpi.com mdpi.com/2072-6694/16/11/2045

Pharmacologic Management of End-of-Life Delirium The authors concluded that both haloperidol and olanzapine were efficacious in reducing delirium symptoms in patients with advanced cancer.