Dexmedetomidine Sublingual Film for the Management of Agitation in Delirium: Safety and Preliminary Efficacy

NCT04382170 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2019P002353
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigator will examine the safety, tolerability, optimal dose, and preliminary efficacy of dexmedetomidine sublingual film in a randomized, double-blind, controlled trial in 40 hospitalized patients with hyperactive delirium (i.e., delirium with agitation) in the Intensive Care Unit (ICU) setting. Specific Aim #1 (safety and tolerability): To examine the incidence of cardiovascular and other side effects following the administration of dexmedetomidine sublingual film in patients hospitalized in the ICU with delirium and agitation in a randomized, double-blind trial (total N=80 patients with delirium \[with or without agitation\], with a goal of administering dexmedetomidine to at least 40 participants with agitation). Hypothesis: Dexmedetomidine sublingual film will be associated with hypotension and/or bradycardia requiring clinical intervention in ≤ 20% (8 of 40) participants. Dexmedetomidine will not be associated with QTc prolongation or non-cardiac adverse events. Specific Aim #2 (preliminary efficacy): To examine the impact of dexmedetomidine sublingual film on agitation and delirium severity. Hypothesis: Dexmedetomidine will lead to reductions in agitation and delirium severity during the follow-up period (co-primary endpoints = 1 and 2 hours post-administration). Specific Aim #3 (optimal dosing): To identify the minimum dose that is effective at reducing agitation and delirium severity without causing significant side effects. Hypothesis: Participants receiving doses of 60 mcg of dexmedetomidine will have a faster time to a reduction in agitation and greater reductions in delirium severity than participants receiving 20 mcg of dexmedetomidine.

Conditions

Delirium

Keywords

agitation; delirium; dexmedetomidine

Outcome Measures

Primary Outcomes (5)

• Change in Heart Rate

  Heart rate will be assessed participant's flowsheet or using the telemetry monitor for the 6 hours following the initial medication administration.

  Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6

• Change in Blood Pressure

  Blood pressure will be assessed participant's flowsheet or using the telemetry monitor/automated blood pressure cuff for the 6 hours following the initial medication administration.

  Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6

• Change in Oxygen Saturation

  Oxygen saturation will be assessed participant's Epic flowsheet or using the telemetry monitor/pulse oximter for the 6 hours following the initial medication administration.

  Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6

• Change in QTc Interval

  An ECG will be performed intermittently over the 6 hour monitoring period, and QTc will be calculated using the Fridericia formula.

  Baseline, Hour 1.5, Hour 3, Hour 4.5, Hour 6

• Self-reported Side Effects

  Incidence of side effects reported for dexmedetomidine in post-marketing surveillance

  Hour 6

Secondary Outcomes (3)

• Change in Agitation

  Baseline, Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 6

• Change in Delirium Severity

  Baseline, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6

• Time to resolution of agitation

  Hour 6

Study Arms (2)

20 mcg

ACTIVE COMPARATOR

Participants randomized to the 20mcg group will receive 20mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 80mcg.

Drug: Dexmedetomidine sublingual film

60 mcg

EXPERIMENTAL

Participants randomized to the 60mcg group will receive 60mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 240mcg.

Drug: Dexmedetomidine sublingual film

Interventions

Dexmedetomidine sublingual film DRUG

Dexmedetomidine sublingual film for the management of agitation in hospitalized patients with delirium.

Also known as: Precedex

20 mcg; 60 mcg

Eligibility Criteria

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

You may qualify if:

• Adults hospitalized on a medical or surgical intensive care unit at MGH
• Diagnosis of delirium, assessed according to DSM-5 criteria (DSM-5)
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive, at screening
• Weight at least 60 kg (132 pounds), at screening
• In the opinion of the study and clinical teams, sufficiently physically healthy to receive dexmedetomidine sublingual film

You may not qualify if:

• Per medical record or team report, diagnoses of:
• Dementia
• Significant traumatic brain injury
• History of stroke, with persistent neurologic deficits
• Presence of any of the following cardiovascular comorbidities
• Sick sinus syndrome
• A resting heart rate of \< 55 beats per minutes or systolic blood pressure (BP) \<100 mmHg or \>160 mmHg or diastolic BP \<70 mmHg or ˃ 95 mmHg at enrollment and prior to dosing.
• Evidence of cardiac ischemia on a 12-lead electrocardiogram (ECG)
• Corrected QT interval of \> 450 msec
• Presence of a permanent pacemaker device
• Per medical record (notes, current medications, flowsheets):
• Second degree (or greater) Atrioventricular (AV) block without a pacemaker
• Known allergy or adverse reaction to dexmedetomidine
• Current use of dexmedetomidine
• Inability to take sublingual dexmedetomidine due to severe agitation, neurological impairment, nil per os (NPO) status, or other cause.

Sponsors & Collaborators

• Jeff C. Huffman, MD: lead
• BioXcel Therapeutics Inc: collaborator

MeSH Terms

Conditions

Delirium; Psychomotor Agitation

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jeff C Huffman, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Cardiac Psychiatry Research Program

Model Details: This study will be a randomized, controlled, 2-arm, double-blinded trial.

Study Record Dates

• First Submitted: April 25, 2020
• First Posted: May 11, 2020
• Study Start: June 1, 2020
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: May 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share