Effects of Dexmedetomidine in Patients With Agitated Delirium in Palliative Care

NCT04824144 | Recruiting Phase 1 DMC

• 1 other identifier: 339633386643463
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this multi-centre phase I/II open-label, single-arm study is to determine the feasibility, optimal dose, and preliminary efficacy of dexmedetomidine to manage agitated delirium among patients near the end of life followed by a palliative care provider in a non-monitored setting. Fifty patients will receive dexmedetomidine (0.4 mcg/kg/hour, titrated up to 1.0 mcg/kg/hour) subcutaneously. Feasibility (recruitment rate, cost), safety (rate of adverse events), dosing, and preliminary efficacy (agitation, delirium severity) will be measured.

Conditions

Hyperactive Delirium; Delirium of Mixed Origin

Keywords

Dexmedetomidine; Agitation; Delirium; Palliative; End of life

Outcome Measures

Primary Outcomes (11)

• Dosing - Therapeutic Dose

  Dose at which the target Richmond Agitation Sedation Scale-Palliative (RASS-PAL) score of -1 ("drowsy"), 0 ("alert and calm"), or +1 ("restless") is achieved. The RASS-PAL is a 10-point scale with scores ranging from -5 (not rousable) to +4 (combative).

  Enrollment to study withdrawal, hospital discharge, or death, whichever is first

• Dosing - Time

  Time (in hours) at which the target Richmond Agitation Sedation Scale-Palliative (RASS-PAL) score of -1 ("drowsy"), 0 ("alert and calm"), or +1 ("restless") is achieved. The RASS-PAL is a 10-point scale with scores ranging from -5 (not rousable) to +4 (combative).

  Enrollment to study withdrawal, hospital discharge, or death, whichever is first

• Number of Participants With Adverse Events - Bradycardia

  Proportion of participants with Bradycardia (two consecutive readings of heart rate (HR)\<40 beats/minute)

  Enrollment to study withdrawal, hospital discharge, or death, whichever is first

• Number of Participants With Adverse Events - Hypotension

  Proportion of participants with Hypotension (systolic blood pressure(SBP) \< 70 mmHg or 40% drop from baseline with lightheadedness or loss of consciousness.

  Enrollment to study withdrawal, hospital discharge, or death, whichever is first

• Number of Participants With Adverse Events - Skin Tolerability

  Proportion of participants with skin intolerability of the infusion site, based on the National Cancer Institute Common Toxicity for Adverse Events.

  Enrollment to study withdrawal, hospital discharge, or death, whichever is first

• Recruitment Rate

  Number of patients enrolled divided by number of patients approached.

  Through study completion, up to 1 year

• Cost

  Comparison of total drug cost of dexmedetomidine (accounting for total dosage administered and duration of therapy) and compare the total cost to that of the alternative first line sedative identified by the treating physician.

  Through study completion, up to 13 months

• Baseline Agitation

  Measured using the Richmond Agitation Sedation Scale-Palliative (RASS-PAL). The RASS-PAL is a 10-point scale with scores ranging from -5 (not rousable) to +4 (combative).

  Baseline

• Baseline Delirium Severity

  Measured using the Nursing Delirium Screening Tool (Nu-DESC). Nu-DESC scores range from 0 to 10, with higher scores indicating worse delirium.

  Baseline

• Change in Agitation

  Measured using the Richmond Agitation Sedation Scale-Palliative (RASS-PAL). RASS-PAL is a 10-point scale with scores ranging from -5 (not rousable) to +4 (combative).

  Measured at Day 1 - 1 hour post administration, one hour post any dose change, and once daily from Day 1 to intervention completion (up to 13 months)

• Change in Delirium Severity

  Measured using the Nursing Delirium Screening Tool (Nu-DESC). Nu-DESC scores range from 0 to 10, with higher scores indicating worse delirium.

  Measured every 8 hours from Day 1 to intervention completion (up to 13 months)

Secondary Outcomes (4)

• Baseline Pain

  Baseline

• Change in Pain From Baseline

  Measured once daily from Day 1 to intervention completion (up to 13 months)

• Baseline Opioid Use

  Measured at Baseline

• Change in Opioid Use From Baseline

  Measured once daily from Day 1 to intervention completion (up to 13 months)

Study Arms (1)

Dexmedetomidine subcutaneous continuous infusion

EXPERIMENTAL

Participants will be given a starting low dose of 0.4 mcg/kg/hr, to be titrated up to a medium dose of 0.7 mcg/kg/hr and potentially up to a maximum dose of 1.0 mcg/kg/hr by subcutaneous infusion until the target RASS-PAL level has been achieved.

Drug: Dexmedetomidine Hydrochloride

Interventions

Dexmedetomidine Hydrochloride DRUG

Dexmedetomidine will be administered by subcutaneous continuous infusion using a Continuous Ambulatory Delivery Device (CADD pump).

Also known as: Dexmedetomidine, Precedex

Dexmedetomidine subcutaneous continuous infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥18 years)
• Admitted to a participating inpatient palliative care unit
• Meeting one of the following criteria:
• Agitated delirium: (i) Richmond Agitation-Sedation Scale for palliative care patients (RASS-PAL) score of +2 or greater and (ii) Confusion Assessment Method (CAM) positive status and (iii) Without a known potentially reversible cause (e.g. hypercalcemia, specific medication infection, etc.), or in whom the patient/Substitute Decision Maker (SDM) has requested not to treat the cause.
• Previous history of delirium (in the last 6 months)
• Patient is within the last two weeks of life and is expected to die during this admission (MRP judgement)

You may not qualify if:

• Hemodynamic instability (systolic blood pressure \<80mmHg)
• Bradyarrhythmia (heart rate \< 60) at baseline
• Patients on verapamil, diltiazem, or beta-blocker (patients are eligible if these medications are stopped prior to receiving dexmedetomidine)

Sponsors & Collaborators

• Bruyère Health Research Institute.: lead
• The Ottawa Hospital: collaborator
• Bruyère Continuing Care: collaborator
• Foothills Medical Centre: collaborator

Study Sites (3)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Bruyère Continuing Care

Ottawa, Ontario, K1N 5C8, Canada

RECRUITING

MeSH Terms

Conditions

Delirium; Psychomotor Agitation; Death

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Psychomotor Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Pathologic Processes

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• James Downar, MDCM, MSc

  Bruyère Health Research Institute.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Downar, MDCM, MSc

CONTACT

6135626262; jdownar@toh.ca

Julie Lapenskie, MSc

CONTACT

6135626262; jlapenskie@bruyere.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Division of Palliative Care

Model Details: The study is a multi-site, open-label, single-arm phase 1/2 proof-of-concept, dose-finding, feasibility, and preliminary efficacy clinical trial.

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: April 1, 2021
• Study Start: January 30, 2024
• Primary Completion: January 31, 2026
• Study Completion: March 31, 2026
• Last Updated: April 15, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)