- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03743649
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
Sao Paulo
-
Barretos, Sao Paulo, Brazil, 14784
- Hosptial de Cancer de Barretos
-
-
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Virginia
-
Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
- [Patients] Admitted to the acute palliative care unit‡
- [Patients] Delirium as per DSM-5 criteria
- [Patients] Hyperactive or mixed delirium with RASS ≥1* in the past 24 h despite efforts to treat potential underlying causes
- [Patients] On scheduled haloperidol for delirium (≤8 mg in the past 24 h) or required ≥4 mg of rescue haloperidol for agitation in the past 24 h
- [Patients] Age 18 years or older
- [Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or significant other (partner as defined by patient)
- [Caregivers] Age 18 years or older
Exclusion Criteria:
- [Patients] History of myasthenia gravis or acute narrow angle glaucoma
- [Patients] History of neuroleptic malignant syndrome or active seizure disorder (with seizure episode within the past week)
- [Patients] History of Parkinson's disease, Alzheimer's or Lewy body dementia
- [Patients] History of prolonged QTc or QTcF interval (>500 ms)† if documented by most recent ECG within the past month
- [Patients] History of hypersensitivity to haloperidol or lorazepam
- [Patients] On scheduled lorazepam within the past 48 h
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group I (haloperidol, placebo)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Group II (lorazepam, placebo)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Group III (haloperidol, lorazepam)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Group IV (placebo, lorazepam)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Richmond Agitation Sedation Scale (RASS) score in patients admitted to an acute palliative care unit (APCU)
Time Frame: Baseline to 24 hours
|
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.
|
Baseline to 24 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rescue medication use
Time Frame: At 24 hours
|
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.
|
At 24 hours
|
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)
Time Frame: At 24 hours
|
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.
|
At 24 hours
|
Perceived comfort as assessed by caregivers and bedside nurses questionnaire
Time Frame: At 24 hours
|
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)
|
At 24 hours
|
Delirium-related distress in caregivers and nurses assessed using Delirium Experience Questionnaire
Time Frame: At 24 hours
|
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.
|
At 24 hours
|
Proxy comfort goal level
Time Frame: Up to 24 hours
|
The achievement of the proxy comfort goal will be assessed.
|
Up to 24 hours
|
Symptom expression assessed using Edmonton Symptom Assessment Scale
Time Frame: At 24 hours
|
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.
|
At 24 hours
|
Delirium severity assessed using Memorial Delirium Assessment Scale
Time Frame: At 24 hours
|
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.
|
At 24 hours
|
Incidence of adverse events
Time Frame: Up to 24 hours
|
Up to 24 hours
|
|
Quality of end-of-life care: questionnaire
Time Frame: 4-8 weeks
|
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.
|
4-8 weeks
|
To identify novel predictive markers of response to haloperidol and lorazepam.
Time Frame: Up to 24 hours
|
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.
|
Up to 24 hours
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David Hui, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Confusion
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Disease Attributes
- Neoplasms
- Delirium
- Recurrence
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Dopamine Agents
- Dopamine Antagonists
- Hypnotics and Sedatives
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Anticonvulsants
- Anti-Dyskinesia Agents
- Haloperidol
- Haloperidol decanoate
- Lorazepam
Other Study ID Numbers
- 2018-0706 (Other Identifier: M D Anderson Cancer Center)
- NCI-2018-02438 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Delirium
-
Efficacy Care R&D LtdHadassah Medical OrganizationUnknownDelirium | Delirium, Cause Unknown | Delirium of Mixed Origin | Delirium Confusional State | Delirium Drug-InducedIsrael
-
Imperial College Healthcare NHS TrustRecruitingCardiac Surgery | Intensive Care Unit Delirium | Post Operative DeliriumUnited Kingdom
-
Oslo University HospitalUniversity of Melbourne; Norwegian Academy of MusicRecruitingDelirium in Old Age | Delirium of Mixed Origin | Delirium Superimposed on Dementia | Delirium Confusional StateNorway
-
Menoufia UniversityCompleted
-
Johns Hopkins UniversityNational Institute on Aging (NIA)Active, not recruitingDelirium | Delirium on Emergence | Hearing Loss | Hearing Loss, High-Frequency | Hearing Loss, Sensorineural | Delirium, Cause Unknown | Hearing Loss, Bilateral | Hearing Disability | Delirium in Old Age | Delirium of Mixed Origin | Delirium Superimposed on Dementia | Delirium Confusional State | Delirium With... and other conditionsUnited States
-
Universidad de SantanderUnknownDelirium of Mixed Origin | Hypoactive Delirium | Hyperactive DeliriumColombia
-
Chinese PLA General HospitalBeijing Tiantan HospitalRecruiting
-
Charite University, Berlin, GermanyBARMERRecruitingDelirium in Old AgeGermany
-
Mayo ClinicCompletedPost-Operative DeliriumUnited States
-
University Hospital, Basel, SwitzerlandInnosuisse - Swiss Innovation AgencyRecruitingPostoperative Delirium (POD)Switzerland
Clinical Trials on Quality-of-Life Assessment
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol Specific | Malignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)RecruitingChildhood Malignant NeoplasmUnited States, Canada, Puerto Rico, Australia, New Zealand
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Malignant Ovarian Epithelial Tumor | Ovarian Carcinosarcoma | Ovarian Brenner Tumor | Ovarian Mucinous... and other conditionsUnited States
-
Wake Forest University Health SciencesWithdrawnLung Metastases | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Recurrent Malignant Mesothelioma | Advanced Malignant Mesothelioma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Recruiting
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | COVID-19 InfectionUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | COVID-19 InfectionUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | Neuropathy | COVID-19 InfectionUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingCervical Carcinoma | Endometrial Carcinoma | Vaginal Carcinoma | Malignant Female Reproductive System Neoplasm | Vulvar CarcinomaUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingMetastatic Colorectal Carcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 and other conditionsUnited States