Nervous System Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

All Conditions

Delirium

Recurrence

Psychomotor Agitation

Confusion

Neurobehavioral Manifestations

Neurologic Manifestations

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Disease Attributes

Anticonvulsants

Antiemetics

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Dyskinesia Agents

Cardiotonic Agents

Lorazepam

Haloperidol

Haloperidol decanoate

Antipsychotic Agents

Dopamine

Dopamine Antagonists

Dopamine Agents

Neurotransmitter Agents

Hypnotics and Sedatives

Anti-Anxiety Agents

GABA Modulators

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.

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.

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.

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.

Placebo

Quality-of-Life Assessment

Questionnaire Administration

David Hui

This phase II/IIII trial studies how well haloperidol and lorazepam work in controlling symptoms of persistent agitated delirium in patients with cancer that has spread to other places in the body undergoing palliative care. Haloperidol and lorazepam may help in controlling symptoms of agitated delirium in patients with cancer and may lessen any distress that their caregivers may be experiencing.

Primary Objectives:

I. To compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on the change in the Richmond Agitation Sedation Scale (RASS) score over 24 hours in patients admitted to an acute palliative care unit (APCU) who do not respond to low-dose haloperidol

Secondary Objectives:

I. To compare the effects of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on (1) rescue medication use; (2) the proportion of patients in the target RASS range (defined as RASS between -2 and 0) as well as the proportion of patients achieving treatment response (defined as RASS reduction of ≥ 1.5 points); (3) perceived comfort as assessed by caregivers and bedside nurses; (4) delirium-related distress in caregivers and nurses (Delirium Experience Questionnaire); (5) achievement of the proxy comfort goal; (6) symptom expression (Edmonton Symptom Assessment Scale \[ESAS\]); (7) delirium severity (Memorial Delirium Assessment Scale \[MDAS\]); (8) adverse effects; and (9) quality of end-of-life care.

II. To identify novel predictive markers of response to haloperidol and lorazepam.

OUTLINE: Patients are randomized to 1 of 4 groups.

GROUP I: Patients receive haloperidol intravenously (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 II: 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 III: 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 IV: 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.

Haloperidol and Lorazepam in Controlling Symptoms of Persistent Agitated Delirium in Patients With Advanced Cancer Undergoing Palliative Care

Strategies for Persistent Agitated Delirium in Palliative Care

The effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal will be compared on the change in the RASS score over 24 hours in patients admitted to an APCU who do not respond to low-dose haloperidol.(RASS between -2 and 0) Will use 2-sided t-tests for four pre-specified paired comparisons, if the required assumptions for this model are met. Non-parametric methods such as Wilcoxon rank-sum test may be used if any assumptions are violated.

Will conduct Bonferroni adjustment for the number of rescue doses. Will perform a comparison among the four arms using analysis of variance (ANOVA), followed by selected pairwise t-test comparisons, or the Kruskal-Wallis test followed by pairwise Wilcoxon rank-sum tests if the data violate assumptions for ANOVA. Will also compare these outcomes longitudinally using linear mixed models, with treatment as a between-patient factor and time as a within-subject factor. Appropriate transformations will be used as needed to satisfy model assumptions.

Will compare the proportions across all four treatment groups using a chi-squared test, followed by selected pairwise chi-squared tests. We will also compare these outcomes longitudinally and include all data after treatment administration using generalized linear mixed models, with treatment as a between-patient factor and time as a within-subject factor.

Will be used for patients with caregivers or nurses listing "agree" or "strongly agree" for patient comfort, proportion of patients with at least 2 on the Udvalg for Kliniske Undersogelser (UKU) scale, and proportion of patients with caregivers listing "excellent" quality of end-of-life care)

Examines both the recalled frequency of 6 delirium symptoms and associated distress in the rater: disorientation to time and place, visual/tactile/auditory hallucinations, delusional thoughts, and psychomotor agitation. It will be administered to family caregivers and nurses daily. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much, and 4=extremely distressed. This assessment will be administered to the blinded caregivers and bedside nurses daily.

The achievement of the proxy comfort goal will be assessed.

Validated and widely used in different clinical settings, including the APCU. It assesses the average symptom intensity of 10 symptoms (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, sleep, and feeling of well-being) over the past 24 hours using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). Because all patients will be delirious, caregivers will be asked to provide their proxy rating of ESAS daily.

Will perform a comparison among the four arms using ANOVA, followed by selected pairwise t-test comparisons, or the Kruskal-Wallis test followed by pairwise Wilcoxon rank-sum tests if the data violate assumptions for ANOVA. Will also compare these outcomes longitudinally using linear mixed models, with treatment as a between-patient factor and time as a within-subject factor. Appropriate transformations will be used as needed to satisfy model assumptions.

Will phone the bereaved caregivers who were most involved in the patient's care within 4-8 weeks of the patient's death to assess the patient's perceived quality of care and quality of life at the end-of-life, on the basis of questions previously used in the Coping with Cancer Study. Specifically, will ask caregivers, "Overall, how would you rate the care (the patient) received at the palliative care unit? Would you say it was excellent, very good, good, fair, or poor?" and "In your opinion, how would you rate the overall quality of (the patient)'s death or last week of life?" using a numeric rating scale from 0 (worst possible) to 10 (best possible). Will also ask them 2 questions related to control of agitation, adapted from the Quality of Death and Dying Questionnaire.

In each of the groups, will identify independent factors that are predictive of response (i.e. RASS reduction of \>= 1.5 points) to treatment using multivariable logistic regression analysis. Will assess the predictive value of plasma biomarkers (i.e. IL-6, IL-8, IL-10, and S100B) in the subset of patients.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Substance Related Disorders

Rare Diseases

Syndrome

Neurotoxicity Syndromes

Acute Graft Versus Host Disease

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

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

Placebo consisting of preservative free 0.9% normal saline given one time by vein.

Questionnaire completion at baseline, and every day while participant is in the palliative care unit. These questions will take about 20 minutes to complete.

Questionnaires

David Hui, MD

This randomized phase II trial studies how well haloperidol with or without lorazepam works in reducing confusion, disorientation, and inability to think or remember clearly (delirium) in patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Palliative therapy with haloperidol and lorazepam may reduce symptoms of delirium and help patients with advanced cancer live more comfortably. It is not yet known whether lorazepam may be an effective treatment for delirium when given with haloperidol.

PRIMARY OBJECTIVES:

I. To compare the effect of single dose lorazepam and placebo as an adjuvant to haloperidol on the intensity of agitation (Richmond Agitation Sedation Scale) over 8 hours.

II. To assess the within-arm effect of single-dose lorazepam or placebo, as an adjuvant agent with haloperidol, on agitation intensity (Richmond Agitation Sedation Scale) over 8 hours in patients admitted to an acute palliative care unit.

SECONDARY OBJECTIVES:

I. To compare the effect of single dose lorazepam and placebo as an adjuvant to haloperidol on (1) delirium related distress in nurses and caregivers, (2) delirium duration, (3) need for rescue doses of neuroleptics, (4) delirium recall, (5) symptom expression (Edmonton Symptom Assessment Scale), (6) communicative capacity, (7) adverse effects, (8) discharge outcomes, and (9) survival in cancer patients.

II. To evaluate proportion of patients who consent and are randomized to study however drop out before being treated or before finishing 8-hour Richmond Agitation Sedation Scale (RASS) assessment; and the reasons of drop-outs will be documented and reported.

III. To explore the changes in biomarker levels in saliva samples (salivary cortisol, cholinesterase, C-reactive protein, interleukin-1 beta, -6, and -10) over time and in association with delirium severity.

IV. To examine the inter-rater reliability of RASS in the Acute Palliative Care Unit (APCU) setting between the bedside nurse and the research nurse at the time of study enrollment.

V. To conduct exploratory analyses on RASS as an outcome. VI. To examine the association among rescue medication use, RASS and perceived comfort by the nurses and caregivers.

VII. To examine the proportion of patients enrolled onto the delirium trial who achieved control of agitation and did not require the randomized study medication.

VIII. To identify patient factors associated with control of agitated delirium.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive lorazepam intravenously (IV) over 1-2 minutes and haloperidol IV every 6 hours or every 1 hour if needed.

ARM II: Patients receive placebo IV over 1-2 minutes and haloperidol IV every 6 hours or every 1 hour if needed.

Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer

A Preliminary Double-Blind Randomized Controlled Trial of Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer Admitted to a Palliative Care Unit

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.

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.

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.

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.

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.

Received single dose of Lorazepam (3 mg IV, once) and Haloperidol (2mg IV, once)

Intervention Group (Lorazepam & Haloperidol)

Received single dose of Haloperidol (2mg IV, once)

Control Group (Placebo & Haloperidol)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

High School or less

College

Completed College

Not Available

Education

Metastatic Cancer

Locally advanced

Recurrent or Persistent

Cancer Stage

GastroIntestinal Cancer

Hematological Cancer

Genitourinary

Head and neck

Breast

Respiratory Cancer

Gynecological

Other

Cancer Type

The Karnofsky Performance Status scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities.

Karnofsky performance status

Intent to treat analysis of 58 participants, 29 for each arm

David Hui, MD/ Associate Professor, Palliative Care Medicine

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

Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points

Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points

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

Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Haloperidol and Lorazepam in Controlling Symptoms of Persistent Agitated Delirium in Patients With Advanced Cancer Undergoing Palliative Care	NCT03743649	Delirium Locally Advance... Metastatic Mali... Recurrent Malig...	Haloperidol Lorazepam Placebo Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer	NCT01949662	Advanced Cancer...	Lorazepam Placebo Haloperidol dec... Questionnaires	18 Years -	M.D. Anderson Cancer Center
Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer	NCT01949662	Advanced Cancer...	Lorazepam Placebo Haloperidol dec... Questionnaires	18 Years -	M.D. Anderson Cancer Center
Haloperidol and Lorazepam in Controlling Symptoms of Persistent Agitated Delirium in Patients With Advanced Cancer Undergoing Palliative Care	NCT03743649	Delirium Locally Advance... Metastatic Mali... Recurrent Malig...	Haloperidol Lorazepam Placebo Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for lorazepam

Every month we try and update this database with for lorazepam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lorazepam

Every month we try and update this database with for lorazepam cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lorazepam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.