Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01949662
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 93
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 84
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if giving lorazepam in combination with haloperidol can help to control the symptoms of delirium in patients with advanced cancer. The safety of this drug combination will also be studied.

In this study, lorazepam is being compared to a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancers	Drug: Lorazepam; Drug: Placebo; Drug: Haloperidol decanoate; Behavioral: Questionnaires	Phase 2

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups:

• If you are in Group 1, you will receive lorazepam.

• If you are in Group 2, you will receive a placebo.

Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving. You will have an equal chance of being in each group.

All patients will receive haloperidol as part of your standard of care. The study doctor can tell you more about haloperidol, how it is designed to work, and about any side effects it may have.

Study Drug Administration:

After you have started receiving haloperidol, you will receive lorazepam or the placebo by vein 1 time over about 1-2 minutes.

Study Tests:

Every day while you are in the palliative care unit, you will be asked to complete the same questionnaires about symptoms and how you are feeling that you were asked at screening. If at any point you recover from your confusion, you will be asked if you remember the confusion and how distressing it was.

Saliva Samples:

While you are in the hospital, saliva samples (about 1/2 a teaspoon) will be collected every day to check for changes in your body's chemical levels. To collect the saliva, a swab will be brushed inside your mouth until enough saliva is gathered on the swab. This should take about 30 seconds to complete.

Length of Study:

You will receive the study drug or placebo 1 time. You will be monitored as part of this study until you leave the palliative care unit. You may go off study at any time that you/your caregiver decides it is in your best interest.

This is an investigational study. Lorazepam is FDA approved and commercially available for the treatment of anxiety, insomnia, and seizures. Its use to help control agitation/delirium is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Preliminary Double-Blind Randomized Controlled Trial of Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer Admitted to a Palliative Care Unit
• Actual Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Aug 26, 2016
• Anticipated Study Completion Date: Jan 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lorazepam + Haloperidol 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	Drug: Lorazepam; 3 mg by vein one time only.; Drug: Haloperidol decanoate; 8 mg/day by vein.; Behavioral: Questionnaires; Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete.; Other Names: Surveys
Active Comparator: Placebo + Haloperidol 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	Drug: Placebo; Placebo consisting of preservative free 0.9% normal saline given one time by vein.; Drug: Haloperidol decanoate; 8 mg/day by vein.; Behavioral: Questionnaires; Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete.; Other Names: Surveys

Outcome Measures

Primary Outcome Measures

1. Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points [Baseline to 8 hours]

   The primary outcome was change in Richmond Agitation-Sedation Scale score from baseline to 8 hours after treatment administration. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.

2. Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points [8 hours]

   Absolute score of Richmond Agitation-Sedation Scale at 8 hr, points. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.

Secondary Outcome Measures

1. Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min [Baseline to 30 minutes]

   Change in Richmond Agitation-Sedation Scale score from baseline to 30 min. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.

2. Number of Participants With Richmond Agitation-Sedation Scale Score >=1 Within 8 hr [Baseline to 8 hours]

   Number of participants with Richmond Agitation-Sedation Scale score >=1 within 8 hr. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic, recurrent, or incurable disease)

2. [Patients] Admitted to Acute Palliative Care Unit (APCU)

3. [Patients] Delirium as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria

4. [Patients] Hyperactive/mixed delirium with RASS >/=2 in the last 24 hours

5. [Patients] On scheduled haloperidol of </=8 mg in the last 24 hours

6. [Patients] Age 18 or older

7. [Patients] Legally Authorized Representative consent

8. [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)

9. [Family Caregivers] Age 18 or older

10. [Family Caregivers] At the patient's bedside at least 4 hours each day during patient delirium episode

11. [Patients and Family Caregivers] Able to communicate in English or Spanish

Exclusion Criteria:

1. [Patients] History of myasthenia gravis or acute narrow angle glaucoma

2. [Patients] History of neuroleptic malignant syndrome

3. [Patients] History of Parkinson's disease or dementia

4. [Patients] Uncontrolled seizure disorder

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

6. [Patients] On regular doses of benzodiazepine or chlorpromazine within the past 48 hours

7. [Patients] Previously documented and persistent QTc prolongation (>500 ms)

8. [Patients] Heart failure exacerbation at the time of enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Hui, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01949662
• Other Study ID Numbers: 2013-0345; NCI-2013-02351; 1R21CA186000-01A1
• First Posted: Sep 24, 2013
• Last Update Posted: Oct 30, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Advanced Cancers; Locally advanced cancer; Metastatic cancer; Recurrent cancer; Incurable cancer; Delirium; Agitation; Lorazepam; Haloperidol; Placebo; Questionnaires; Surveys; Acute palliative care unit
• Additional relevant MeSH terms: Neoplasms; Delirium; Lorazepam; Haloperidol; Haloperidol decanoate

Study Results

Participant Flow

Recruitment Details	Patients were recruited between 1/2014 and 6/2016 from MD Anderson Cancer Center with active cancer diagnosis, having age >=18, with Delirium with Richmond Agitation-Sedation Scale score of >=2 and receiving scheduled Haloperidol 1-8 mg/day.
Pre-assignment Detail	3 patients were excluded before randomization. 1 died and 2 were ineligible.

Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)	Control Group (Placebo & Haloperidol)
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)	Received single dose of Haloperidol (2mg IV, once)
Period Title: Overall Study
STARTED	47	43
COMPLETED	29	29
NOT COMPLETED	18	14

Baseline Characteristics

Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)	Control Group (Placebo & Haloperidol)	Total
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)	Received single dose of Haloperidol (2mg IV, once)	Total of all reporting groups
Overall Participants	29	29	58
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	66	64	65
Sex: Female, Male (Count of Participants)
Female	11 37.9%	16 55.2%	27 46.6%
Male	18 62.1%	13 44.8%	31 53.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.9%	0 0%	2 3.4%
Not Hispanic or Latino	27 93.1%	29 100%	56 96.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 13.8%	4 13.8%	8 13.8%
White	23 79.3%	23 79.3%	46 79.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 6.9%	2 6.9%	4 6.9%
Region of Enrollment (Count of Participants)
United States	29 100%	29 100%	58 100%
Education (Count of Participants)
High School or less	7 24.1%	8 27.6%	15 25.9%
College	11 37.9%	6 20.7%	17 29.3%
Completed College	10 34.5%	14 48.3%	24 41.4%
Not Available	1 3.4%	1 3.4%	2 3.4%
Cancer Stage (Count of Participants)
Metastatic Cancer	20 69%	26 89.7%	46 79.3%
Locally advanced	1 3.4%	0 0%	1 1.7%
Recurrent or Persistent	8 27.6%	3 10.3%	11 19%
Cancer Type (Count of Participants)
GastroIntestinal Cancer	9 31%	4 13.8%	13 22.4%
Hematological Cancer	8 27.6%	2 6.9%	10 17.2%
Genitourinary	2 6.9%	1 3.4%	3 5.2%
Head and neck	0 0%	1 3.4%	1 1.7%
Breast	0 0%	5 17.2%	5 8.6%
Respiratory Cancer	4 13.8%	10 34.5%	14 24.1%
Gynecological	2 6.9%	2 6.9%	4 6.9%
Other	4 13.8%	4 13.8%	8 13.8%
Karnofsky performance status (Count of Participants)
10%	7 24.1%	5 17.2%	12 20.7%
20%	15 51.7%	12 41.4%	27 46.6%
30%	4 13.8%	10 34.5%	14 24.1%
40%	3 10.3%	2 6.9%	5 8.6%

Outcome Measures

1. Primary Outcome

Title	Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points
Description	The primary outcome was change in Richmond Agitation-Sedation Scale score from baseline to 8 hours after treatment administration. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.
Time Frame	Baseline to 8 hours

Outcome Measure Data

Analysis Population Description

Intent to treat 58 participants, a total of 29 for each arm; 3 participants were lost to follow up from each arm.

Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)	Control Group (Placebo & Haloperidol)
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)	Received single dose of Haloperidol (2mg IV, once)
Measure Participants	26	26
Mean (95% Confidence Interval) [score on a scale]	-4.1	-2.3

2. Primary Outcome

Title	Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points
Description	Absolute score of Richmond Agitation-Sedation Scale at 8 hr, points. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.
Time Frame	8 hours

Outcome Measure Data

Analysis Population Description

Intent to treat 58 participants, a total of 29 for each arm; 3 participants were lost to follow up from each arm.

Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)	Control Group (Placebo & Haloperidol)
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)	Received single dose of Haloperidol (2mg IV, once)
Measure Participants	26	26
Mean (95% Confidence Interval) [score on a scale]	-2.5	-0.7

3. Secondary Outcome

Title	Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min
Description	Change in Richmond Agitation-Sedation Scale score from baseline to 30 min. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.
Time Frame	Baseline to 30 minutes

Outcome Measure Data

Analysis Population Description

Intent to treat 58 participants, a total of 29 for each arm

Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)	Control Group (Placebo & Haloperidol)
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)	Received single dose of Haloperidol (2mg IV, once)
Measure Participants	29	29
Mean (95% Confidence Interval) [score on a scale]	-3.6	-1.6

4. Secondary Outcome

Title	Number of Participants With Richmond Agitation-Sedation Scale Score >=1 Within 8 hr
Description	Number of participants with Richmond Agitation-Sedation Scale score >=1 within 8 hr. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient.
Time Frame	Baseline to 8 hours

Outcome Measure Data

Analysis Population Description

Intent to treat 58 participants, a total of 29 from each arm

Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)	Control Group (Placebo & Haloperidol)
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)	Received single dose of Haloperidol (2mg IV, once)
Measure Participants	29	29
Count of Participants [Participants]	8 27.6%	22 75.9%

Adverse Events

Time Frame	Baseline up to 3 days
Adverse Event Reporting Description	UKU (Udvalg for Kliniske Undersøgelser ) Adverse events Assessment. Total intent to treat = 58 (29+29); Total Participants used for the All Cause Mortality in both Arms, Intervention (47), and Placebo (43). The total number of deaths in the Intervention Group were 10 which includes 9 from the incomplete category and 1 from the complete category. The total number of deaths in the Control Group were 10 which includes 7 from the incomplete category and 3 from the complete category.
Arm/Group Title	Intervention Group (Lorazepam & Haloperidol)		Control Group (Placebo & Haloperidol)
Arm/Group Description	Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)		Received single dose of Haloperidol (2mg IV, once)
All Cause Mortality
	Intervention Group (Lorazepam & Haloperidol)		Control Group (Placebo & Haloperidol)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/47 (21.3%)		10/43 (23.3%)
Serious Adverse Events
	Intervention Group (Lorazepam & Haloperidol)		Control Group (Placebo & Haloperidol)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Intervention Group (Lorazepam & Haloperidol)		Control Group (Placebo & Haloperidol)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/29 (10.3%)		4/29 (13.8%)
Musculoskeletal and connective tissue disorders
Hypokinesia	3/29 (10.3%)		4/29 (13.8%)
Hyperkinesia	1/29 (3.4%)		2/29 (6.9%)
Akathisia	3/29 (10.3%)		1/29 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.