Dexmedetomidine for Delirium

(MINDDS II Trial)

Recruiting at 15 trial locations

Overseen By Ariel Mueller, MA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Massachusetts General Hospital

Disqualifiers: Alzheimer's, Severe liver failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

Duration: 3 days

1800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how dexmedetomidine, a sedative, affects delirium (a state of confusion) and recovery after heart surgery. Participants are divided into three groups: one receiving intravenous dexmedetomidine, another receiving sublingual dexmedetomidine, and a third receiving a placebo. The trial aims to determine if the medication reduces delirium and improves post-surgery outcomes. Individuals aged 60 or older, undergoing heart surgery with a planned ICU stay, may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the drug dexmedetomidine has mixed safety results. Some studies found it might increase the risk of delirium (confusion and agitation) in ICU patients, with one study reporting this in 28.28% of patients. However, other research suggests dexmedetomidine can help manage agitation and lower the risk of delirium in some cases.

Regarding side effects, patients using dexmedetomidine experienced more cases of bradycardia (a slower than normal heart rate), with one study noting it in 16.5% of patients. This rate is higher compared to those who did not receive the drug.

For the sublingual form (under-the-tongue) of dexmedetomidine, studies have shown it can reduce agitation, which is promising. While specific safety data for sublingual use is less common, the overall safety of dexmedetomidine is well-known from its use in other medical settings.

This drug is in a later phase of testing, meaning it has already gone through earlier safety checks. So, a good amount of safety information is available, although risks like bradycardia remain important to consider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for delirium, which typically involves antipsychotics or benzodiazepines, dexmedetomidine offers a unique approach. This drug acts on the alpha-2 adrenergic receptors, providing sedation without the respiratory depression that can occur with traditional sedatives. Researchers are excited about dexmedetomidine because it can be administered intravenously or sublingually, offering flexibility in treatment. Additionally, it provides a calming effect that might reduce the duration and severity of delirium symptoms more effectively than existing options.

What evidence suggests that this trial's treatments could be effective for postoperative delirium?

This trial will compare different methods of administering dexmedetomidine to manage delirium in ICU patients. Research shows that dexmedetomidine can calm and reduce restlessness in ICU patients with severe confusion, known as hyperactive delirium. Studies have found that it may also shorten the duration of agitation, aiding recovery after surgery. For heart surgery patients, dexmedetomidine has effectively reduced the chances of post-operative confusion. While some research suggests it might increase the risk of confusion in general ICU use, evidence also indicates that its calming effects may improve survival. Overall, dexmedetomidine appears promising in managing confusion symptoms in surgical patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Oluwaseun Johnson-Akeju, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for elderly patients who have recently undergone cardiac surgery and are at risk of developing delirium, a common postoperative complication. Participants must meet certain health standards to be eligible.

Inclusion Criteria

I am 60 years old or older.

I am scheduled for heart surgery that will use a heart-lung machine.

I am scheduled to stay in the ICU after my surgery.

Exclusion Criteria

Co-enrollment in other interventional studies that, in the opinion of the site investigator and/or PI, might interfere with study participation, collection, or interpretation of the study data

I am scheduled for surgery that will stop my blood circulation.

I have severe impairments from brain damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either intravenous or sublingual dexmedetomidine or placebo nightly for the first three nights in the ICU

3 days

Inpatient ICU stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of delirium, pain, and global health

365 days

In-person and telephonic follow-ups at 30, 180, and 365 days

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine
• Placebo

Trial Overview

The MINDDS II study is testing whether dexmedetomidine, given either intravenously or sublingually at night, can reduce the incidence of delirium and improve recovery after heart surgery compared to placebo.

How Is the Trial Designed?

Group I: Sublingual Dexmedetomidine Experimental Treatment 2 Interventions

After admission to the ICU and discontinuation of mechanical ventilation, sublingual dexmedetomidine (120 μg) and an intravenous placebo (0.9% saline over 40 minutes) will be administered nightly for the first three nights while the patient is in the intensive care unit.

Group II: Intravenous Dexmedetomidine Experimental Treatment 2 Interventions

After admission to the ICU and discontinuation of mechanical ventilation, intravenous dexmedetomidine (1 μg/kg over 40 minutes, a maximal dose of 80 μg) and a sublingual placebo (inert film) will be administered nightly for the first three nights while the patient is in the intensive care unit.

Group III: Placebo Placebo Group 2 Interventions

After admission to the ICU and discontinuation of mechanical ventilation, an intravenous placebo (0.9% saline over 40 minutes) and a sublingual placebo (inert film) will be administered nightly for the first three nights while the patient is in the intensive care unit.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

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 of 30 patients with liver dysfunction undergoing percutaneous arterial chemoembolization for hepatocellular carcinoma, dexmedetomidine sedation was successfully used in all cases, demonstrating its feasibility for this procedure.

The sedation was generally safe, with only minor adverse events reported in 3 patients, and no serious complications requiring treatment, indicating that dexmedetomidine can be a reliable option for sedation in patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. Komemushi, A., Suzuki, S., Sano, A., et al.[2015]

A meta-analysis of 10 trials involving 2,286 participants found that perioperative dexmedetomidine significantly reduced the risk of postoperative delirium by 47% compared to placebo or other sedation methods.

Higher infusion rates of dexmedetomidine (above 0.2 μg/kg/h) further decreased the risk of delirium by 34%, while lower rates (below 0.2 μg/kg/h) showed an even greater reduction of 62%, indicating that the dosage plays a crucial role in its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative dexmedetomidine and postoperative delirium in non-cardiac surgery: a meta-analysis. Ming, S., Zhang, X., Gong, Z., et al.[2021]

In a study of 60 cardiac surgery patients, dexmedetomidine significantly reduced the duration of delirium (26.5 hours) compared to haloperidol (36.3 hours), indicating its efficacy in managing postoperative delirium.

Dexmedetomidine also led to a shorter ICU stay (2.73 days) compared to haloperidol (3.5 days), while allowing for better sedation levels without causing respiratory depression, although it was associated with dose-dependent bradycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of delirium in the early postoperative period after cardiac surgery]. Eremenko, AA., Chernova, EV.[2014]

Dexmedetomidine is commonly used as a safe sedative during surgeries, but there are rare cases where it can lead to serious complications, such as cardiac arrest.

In this report, a 76-year-old woman experienced cardiac arrest during a pacemaker lead extraction procedure while being treated with dexmedetomidine, highlighting the need for careful monitoring in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Shah, AN., Koneru, J., Nicoara, A., et al.[2013]

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]

Dexmedetomidine is an effective sedative for mechanically ventilated patients and during surgical procedures, requiring less rescue sedation compared to placebo, which indicates its efficacy in maintaining optimal sedation levels.

It is generally well tolerated, with a lower incidence of postoperative delirium and no respiratory depression, although it can cause hypotension and bradycardia, which typically resolve without treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. Hoy, SM., Keating, GM.[2022]

Dexmedetomidine, a selective α2 agonist used for sedation in ICU patients, may help reduce the risk of delirium compared to other sedation methods, although the evidence is limited due to the small number of studies (only three trials) and their varying designs.

While dexmedetomidine appears to allow for less deep sedation and reduced use of benzodiazepines—both of which are linked to higher delirium risk—more research is needed to confirm its effectiveness in preventing delirium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining the Role of Dexmedetomidine in the Prevention of Delirium in the Intensive Care Unit. Nelson, S., Muzyk, AJ., Bucklin, MH., et al.[2018]

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]

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This study investigated the risk and outcomes of delirium in ICU patients who received DEX within 24 hours preceding a delirium assessment, compared to those ...

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In regard to safety, subjects randomized to dexmedetomidine experienced significantly more bradycardia (16.5% versus 6.1%, p = 0.006) and significantly less ...

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The use of dexmedetomidine was associated with reduced risk of delirium (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54–0.75; very low-quality ...