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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how dexmedetomidine, a sedative, might help manage agitated delirium in patients nearing the end of life. Researchers aim to determine the best dose and assess its safety and effectiveness when administered subcutaneously. They seek patients admitted to a palliative care unit who experience severe confusion and agitation without a treatable cause for their symptoms. The study aims to improve comfort for those in their final days. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that dexmedetomidine is likely to be safe for humans?

Research has shown that dexmedetomidine is generally safe in certain situations. Some studies suggest it can reduce confusion in patients after heart surgery, indicating it might help with similar symptoms in other cases.

However, other studies found that dexmedetomidine might increase confusion in very sick patients. This risk varies based on the situation and how the drug is used.

Most evidence comes from studies with patients in intensive care or after surgery, where the drug helps calm them. In these cases, dexmedetomidine is usually well-tolerated, but monitoring patients closely is important to catch any side effects early.

This trial is in the early stages (Phase 1/2), meaning researchers are still determining the best dose and possible side effects for this specific use. In these early trials, safety is the main focus, and participants are closely watched for any negative reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for delirium?

Unlike the standard treatments for delirium, which often involve antipsychotics and sedatives, dexmedetomidine offers a novel approach by acting on alpha-2 adrenoceptors. This mechanism helps calm patients without the heavy sedation associated with other drugs, potentially allowing for a more alert state. Additionally, dexmedetomidine is administered through a subcutaneous infusion, providing a steady, controlled release that can be precisely adjusted to achieve desired sedation levels. Researchers are particularly excited about its potential to manage delirium with fewer side effects, improving patient outcomes and comfort.

What evidence suggests that dexmedetomidine might be an effective treatment for agitated delirium?

Research has shown that dexmedetomidine can lower the risk of confusion and disorientation (delirium) in patients after heart surgery. Some studies found it could reduce the chance of delirium by about 24%. This trial will investigate the effects of dexmedetomidine administered as a subcutaneous continuous infusion. While dexmedetomidine may calm patients, especially in end-of-life care, results can vary, and some studies have shown mixed outcomes. Overall, dexmedetomidine appears promising, but more research is needed to confirm its effectiveness in different situations. ^{6 7 8 9 10}

Who Is on the Research Team?

James Downar, MDCM, MSc

Principal Investigator

Bruyère Health Research Institute.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Bruyère Health Research Institute.

Lead Sponsor

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+

Published Research Related to This Trial

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 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, 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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12149363/

The Effects of Dexmedetomidine on Postoperative Delirium ... Overall, dexmedetomidine reduces the risk of delirium by 24% in postoperative cardiac patients; however, some uncertainty accompanied this ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40441198/

Dexmedetomidine increases the risk of delirium in critically ... Among 78,364 patients analyzed, 22,159 (28.28%) had positive delirium records. Propensity matching yielded 4666 patients (2333 per treatment ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053077025004355

Review Article Effect of dexmedetomidine on the incidence ... Dexmedetomidine was effective to reduce the incidence of postoperative delirium following cardiac surgery when given either intraoperative or postoperative.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02809937

Dexmedetomidine and Long-term Outcome in Elderly ... The occurrence of delirium is associated with worse long-term outcomes including worse functional recovery, decline in cognitive function, and increased ...

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-023-04618-z

Use of dexmedetomidine in critical-ill patients: is it time to look ... The analysis suggested that the utilization of dexmedetomidine may have a higher probability of 90-day mortality in patients aged ≤ 65 years.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4157475/

Efficacy and Safety of Dexmedetomidine for Postoperative ... This preliminary study suggests that dexmedetomidine as a postoperative sedative agent is as sociated with significantly lower rates of delirium after cardiac ...

7. journals.lww.com journals.lww.com/md-journal/fulltext/2025/05300/dexmedetomidine_increases_the_risk_of_delirium_in.17.aspx

Dexmedetomidine increases the risk of delirium in critically DEX administration significantly increased the risk of delirium (P < .001). It was also associated with extended ICU stay (P < .001) but ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299925004777

Delirium risk associated with Esketamine, Sevoflurane ... Our findings demonstrate that propofol, sevoflurane, and dexmedetomidine are significantly associated with the risk of delirium, whereas esketamine did not ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03012984

Dexmedetomidine Supplemented Analgesia and Incidence ... Studies have shown that, for ICU patients requiring mechanical ventilation, sedation with dexmedetomidine reduces the incidence of delirium when compared with ...

10. cardiothoracicsurgery.biomedcentral.com cardiothoracicsurgery.biomedcentral.com/articles/10.1186/s13019-025-03360-7

Dexmedetomidine for delirium prevention in adult patients ... Dexmedetomidine is safe for cardiac surgery patients and to some extent reduces the incidence of delirium in cardiac surgery patients, which is more important ...