Dexmedetomidine for Delirium

Recruiting at 4 trial locations

Overseen By Julie Lapenskie, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Verapamil, Diltiazem, Beta-blockers

Disqualifiers: Hemodynamic instability, Bradyarrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 13 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are taking verapamil, diltiazem, or a beta-blocker, you will need to stop these medications before starting the trial.

What data supports the effectiveness of the drug Dexmedetomidine for treating delirium?

Dexmedetomidine has been used to treat delirium in intubated critically ill patients, and there is a hypothesis that it might be better than haloperidol (a common delirium treatment) for non-intubated patients with hyperactive delirium. However, the evidence is still being studied, and its effectiveness for non-intubated patients is not yet confirmed. ^{1 2 3 4 5}

Is dexmedetomidine safe for use in humans?

Dexmedetomidine, used under names like Precedex and Dexdor, is generally considered safe for humans, but it can cause side effects like low blood pressure (hypotension) and slow heart rate (bradycardia). These side effects are manageable with medication, and the drug has been well-tolerated in both adults and children in various clinical settings. ^{1 5 6 7 8}

What makes the drug dexmedetomidine unique for treating delirium?

Dexmedetomidine is unique because it is a highly selective alpha2 adrenoreceptor agonist that provides sedation with minimal respiratory depression, unlike other sedatives. It allows patients to be easily aroused and maintains some memory and cognition, making it effective for controlling delirium in ICU patients without the respiratory side effects common with other sedatives. ^{3 5 9 10 11}

Research Team

James Downar, MDCM, MSc

Principal Investigator

Bruyère Research Institute

Eligibility Criteria

This trial is for adults with agitated delirium in palliative care, who've had delirium recently or are in their last two weeks of life. They must have a specific level of agitation and confusion without reversible causes, or choose not to treat such causes. It's not for those with very low blood pressure, slow heart rate, or taking certain heart medications unless stopped before the trial.

Inclusion Criteria

The patient is expected to pass away within the next two weeks.

Meeting one of the following criteria:

I am experiencing severe confusion or agitation without a treatable cause.

Exclusion Criteria

Your heart rate is less than 60 beats per minute when measured before the study.

I am not currently taking verapamil, diltiazem, or beta-blockers, or I can stop them before starting dexmedetomidine.

My blood pressure is stable and not below 80mmHg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexmedetomidine subcutaneously, starting at 0.4 mcg/kg/hr, titrated up to 1.0 mcg/kg/hr to manage agitated delirium

Up to 13 months

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexmedetomidine Hydrochloride

Trial Overview The study tests dexmedetomidine's ability to manage agitated delirium at the end-of-life stage. Fifty patients will receive varying doses subcutaneously in a non-monitored setting. The focus is on finding the right dose and seeing how well it works by looking at recruitment rates, costs, safety through adverse events tracking, and its effect on agitation and severity of delirium.

Participant Groups

Group I: Dexmedetomidine subcutaneous continuous infusion Experimental Treatment 1 Intervention

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.

Dexmedetomidine Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Precedex for:

• Sedation for mechanically ventilated patients
• Procedural sedation
• Acute agitation associated with schizophrenia or bipolar disorder

Approved in European Union as Dexdor for:

• Sedation for mechanically ventilated patients
• Procedural sedation

Approved in Canada as Dexmedetomidine Hydrochloride for:

• Sedation for mechanically ventilated patients
• Procedural sedation

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Bruyere Research Institute

Lead Sponsor

Trials

35

Recruited

2,024,000+

Bruyère Continuing Care

Collaborator

Trials

1

Recruited

50+

Elisabeth Bruyere Hospital

Collaborator

Trials

1

Recruited

50+

Princess Margaret Hospital, Canada

Collaborator

Trials

121

Recruited

40,000+

Providence Care Hospital

Collaborator

Trials

1

Recruited

50+

The Ottawa Hospital

Collaborator

Trials

97

Recruited

64,000+

Élisabeth Bruyère Hospital

Collaborator

Trials

1

Recruited

50+

Providence Care

Collaborator

Trials

3

Recruited

370+

Foothills Medical Centre

Collaborator

Trials

21

Recruited

20,200+

Findings from Research

This systematic review protocol aims to evaluate the efficacy and safety of dexmedetomidine in managing delirium in critically ill patients, addressing conflicting evidence from previous studies.

The review will include all relevant randomized clinical trials and utilize rigorous methods, including the Cochrane risk of bias tool and GRADE assessment, to ensure high-quality evidence for clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine for the management of delirium in critically ill patients-A protocol for a systematic review. Maagaard, M., Barbateskovic, M., Perner, A., et al.[2023]

This systematic review protocol aims to evaluate the efficacy of dexmedetomidine in preventing delirium in critically ill patients by comparing it to a placebo, with a focus on clinical outcomes and incidence rates.

The review will include all randomized trials and utilize rigorous methods, including the Cochrane risk of bias tool and GRADE for assessing evidence quality, to ensure reliable results that can inform clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine for the prevention of delirium in critically ill patients - A protocol for a systematic review. Maagaard, M., Barbateskovic, M., Perner, A., et al.[2023]

In a study of 263 critically ill elderly patients, dexmedetomidine was found to provide better sedation for delirium control compared to olanzapine, with lower RASS scores indicating less agitation.

However, olanzapine was associated with fewer adverse effects, such as respiratory depression and hypotension, making it a safer option for managing delirium in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are dexmedetomidine and olanzapine suitable to control delirium in critically ill elderly patients? A retrospective cohort study. Liu, S., Zhao, R., Yang, R., et al.[2021]

This study will compare the efficacy and safety of dexmedetomidine versus haloperidol for treating nocturnal hyperactive delirium in non-intubated critically ill patients, involving 100 participants in a randomized controlled trial.

The primary goal is to determine which medication better achieves targeted sedation levels within 2 hours, potentially establishing dexmedetomidine as a new treatment option for hyperactive delirium in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine versus haloperidol for sedation of non-intubated patients with hyperactive delirium during the night in a high dependency unit: study protocol for an open-label, parallel-group, randomized controlled trial (DEX-HD trial). Minami, T., Watanabe, H., Kato, T., et al.[2023]

In a study of 19 patients aged 65 on average who underwent various cardiac surgeries, continuous infusion of dexmedetomidine was found to effectively sedate patients without significantly affecting heart rate or other hemodynamic parameters, except for a decrease in blood pressure.

Dexmedetomidine caused a reduction in systemic vascular resistance and mixed venous oxygen saturation, indicating its vaso-dilating effects, which suggests it can be safely used as a sedative in the post-operative setting after cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of dexmedetomidine in patients after cardiac surgery. Ishikawa, S., Kugawa, S., Neya, K., et al.[2006]

Dexmedetomidine (DEX) is an effective sedative with neuroprotective properties, showing improved outcomes in ICU patients and potential as a non-opioid analgesic, which is important for reducing opioid-related side effects.

While DEX has significant benefits for the nervous system, clinicians must be aware of potential adverse effects like hypotension and bradycardia, which can be managed with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as an Analgesic Agent with Neuroprotective Properties: Experimental and Clinical Aspects. Bozorgi, H., Zamani, M., Motaghi, E., et al.[2021]

Dexmedetomidine hydrochloride (Precedex) is a highly selective alpha(2)-adrenoreceptor agonist that effectively induces sedation and analgesia in ICU patients, with a significantly higher effective rate for reducing the need for additional sedatives (90.9% vs. 44.6% for placebo) and analgesics (87.3% vs. 75.0% for placebo).

The drug acts primarily through the alpha(2A)-receptor subtype in the locus coeruleus, leading to its sedative effects, but it can also cause adverse events such as hypertension and hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dexmedetomidine hydrochloride (Precedex), a new sedative in intensive care, its pharmacological characteristics and clinical study result]. Taiji, K.[2019]

In a study involving 91 pediatric patients, dexmedetomidine was found to be a well-tolerated alternative sedative for non-intubated moderate or deep sedation, with a low incidence of serious adverse events.

While respiratory depression and hypotension were the most common treatment-emergent adverse events, they were manageable and consistent with dexmedetomidine's known safety profile, indicating its potential for safe use in children during elective procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. Jooste, EH., Hammer, GB., Reyes, CR., et al.[2020]

Dexmedetomidine, a selective α-2 receptor agonist, shows promise in preventing and treating delirium in ICU patients due to its unique mechanism of action that provides sedation without significant respiratory depression.

The review of eight clinical trials indicates that dexmedetomidine may help manage ICU-associated delirium effectively, but further large-scale studies are needed to confirm its role and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. Mo, Y., Zimmermann, AE.[2022]

Dexmedetomidine is an effective sedative and analgesic that works quickly, reaching peak effects within one hour, and has shown comparable efficacy to haloperidol and benzodiazepines for treating delirium in intensive care settings.

It has an opioid-sparing effect, meaning it can reduce the need for opioids while enhancing pain relief, making it a valuable option for palliative care, particularly in managing delirium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: dexmedetomidine: does it have potential in palliative medicine? Prommer, E.[2013]

Dexmedetomidine (DEX) was successfully used to manage hyperactive delirium in a 28-year-old male ICU patient after a severe hepatic injury, demonstrating its efficacy in controlling delirium when other sedatives failed.

DEX is advantageous because it provides sedation with minimal respiratory depression and helps maintain memory and cognition, making it a safer option for ICU patients at risk of postoperative delirium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of dexmedetomidine in a critically ill patient with hyperactive delirium: a case report]. Tamada, N., Matsuzaki, S., Matsuda, T., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine for the management of delirium in critically ill patients-A protocol for a systematic review. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine for the prevention of delirium in critically ill patients - A protocol for a systematic review. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Are dexmedetomidine and olanzapine suitable to control delirium in critically ill elderly patients? A retrospective cohort study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine versus haloperidol for sedation of non-intubated patients with hyperactive delirium during the night in a high dependency unit: study protocol for an open-label, parallel-group, randomized controlled trial (DEX-HD trial). [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of dexmedetomidine in patients after cardiac surgery. [2006]

6. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as an Analgesic Agent with Neuroprotective Properties: Experimental and Clinical Aspects. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

[Dexmedetomidine hydrochloride (Precedex), a new sedative in intensive care, its pharmacological characteristics and clinical study result]. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Review article: dexmedetomidine: does it have potential in palliative medicine? [2013]

11. Japan pubmed.ncbi.nlm.nih.gov

[Use of dexmedetomidine in a critically ill patient with hyperactive delirium: a case report]. [2013]