Dexmedetomidine for Delirium

(MINDDS II Trial)

Recruiting in Palo Alto (17 mi)

+11 other locations

Overseen by Oluwaseun Johnson-Akeju, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Massachusetts General Hospital

Disqualifiers: Alzheimer's, Severe liver failure, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a pragmatic phase III, randomized, blinded, double placebo-controlled, three-arm trial of elderly patients following cardiac surgery to assess the relationship between nighttime intravenous (IV) and sublingual dexmedetomidine on postoperative delirium and functional outcomes after surgery.

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.

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

Research suggests that Dexmedetomidine, a sedative, may help prevent delirium by avoiding deep sedation and reducing the use of benzodiazepines, which are linked to higher delirium risk. However, more studies are needed to confirm its effectiveness specifically for delirium treatment. ^{1 2 3 4 5}

Is dexmedetomidine safe for use in humans?

Dexmedetomidine is generally considered safe for use in humans, but it can cause side effects like respiratory depression (slowed breathing) and low blood pressure. In rare cases, it has been associated with serious events like cardiac arrest, especially in patients with certain heart conditions. ^{1 6 7 8 9}

How does the drug dexmedetomidine differ from other treatments for delirium?

Dexmedetomidine is unique because it is a highly selective alpha(2)-adrenergic receptor agonist that provides sedation without significant respiratory depression, unlike other sedatives. It may also reduce the need for additional sedatives like propofol and morphine, which can increase the risk of delirium. ^{1 5 9 10 11}

Research Team

Oluwaseun Johnson-Akeju, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dexmedetomidine (Sedative)
• Placebo (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.

Participant Groups

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+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

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]

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, 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 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]

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]

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 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]

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]

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. China pubmed.ncbi.nlm.nih.gov

Perioperative dexmedetomidine and postoperative delirium in non-cardiac surgery: a meta-analysis. [2021]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Treatment of delirium in the early postoperative period after cardiac surgery]. [2014]

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

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

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

Defining the Role of Dexmedetomidine in the Prevention of Delirium in the Intensive Care Unit. [2018]

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

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. [2013]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Japan pubmed.ncbi.nlm.nih.gov

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. [2015]

10. Japan pubmed.ncbi.nlm.nih.gov

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

11. New Zealand 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. [2022]