Clinical trial NCT01949662: Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Cancers
Keywords: Advanced Malignant Solid Neoplasm
Delirium
Hematopoietic and Lymphoid Cell Neoplasm
Locally Advanced Malignant Solid Neoplasm
Malignant Solid Neoplasm
Neurotoxicity Syndrome
Questionnaires
Surveys
Acute palliative care unit
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-09-24
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* PATIENTS:
* Diagnosis of advanced cancer (defined as locally advanced, metastatic, recurrent, or incurable disease)
* Admitted to Acute Palliative Care Unit (APCU)
* Delirium as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV- TR) criteria
* Hyperactive/mixed delirium with RASS \>= 2 in the last 24 hours
* On scheduled haloperidol of =\< 8 mg in the last 24 hours
* Legally authorized representative consent
* FAMILY CAREGIVERS:
* Patient's spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
* Age 18 or older
* At the patient's bedside at least 4 hours each day during patient delirium episode
* Patients and family caregivers able to communicate in English or Spanish

Exclusion Criteria:

* PATIENTS
* History of myasthenia gravis or acute narrow angle glaucoma
* History of neuroleptic malignant syndrome
* History of Parkinson's disease or dementia
* Uncontrolled seizure disorder
* History of hypersensitivity to haloperidol or benzodiazepine
* On regular doses of benzodiazepine or chlorpromazine within the past 48 hours
* Previously documented and persistent corrected QT (QTc) prolongation (\> 500 ms)
* Heart failure exacerbation at the time of enrollment

Primary outcomes:
measure: Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points
timeFrame: Baseline to 8 hours
measure: Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points
timeFrame: 8 hours
Secondary outcomes:
measure: Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min
timeFrame: Baseline to 30 minutes
measure: Number of Participants With Richmond Agitation-Sedation Scale Score >=1 Within 8 hr
timeFrame: Baseline to 8 hours
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Hui, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hui D, Frisbee-Hume S, Wilson A, Dibaj SS, Nguyen T, De La Cruz M, Walker P, Zhukovsky DS, Delgado-Guay M, Vidal M, Epner D, Reddy A, Tanco K, Williams J, Hall S, Liu D, Hess K, Amin S, Breitbart W, Bruera E. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017 Sep 19;318(11):1047-1056. doi: 10.1001/jama.2017.11468.