Dexmedetomidine for Postoperative Cognitive Dysfunction

(CODEX Trial)

Recruiting at 7 trial locations

Overseen By Stephen Choi, MD,FRCPC,MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Cognitive dysfunction, Heart block, Cirrhosis, others

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

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

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 12 hours

2400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Dexmedetomidine Hydrochloride, a sedative medication, can prevent memory problems that some people experience after heart surgery. These memory issues, known as postoperative cognitive dysfunction (POCD), can affect daily life and recovery. The trial compares Dexmedetomidine to standard care, aiming to improve recovery and reduce hospital stays. Individuals scheduled for heart surgeries, such as bypass or valve replacement, who will recover in a specialized heart care unit, might be suitable candidates. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

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 is the safety track record for Dexmedetomidine Hydrochloride?

Research shows that dexmedetomidine (DEX) is generally safe for people. Studies have found that DEX can help reduce confusion in patients after surgery and may support brain function, possibly protecting the brain post-surgery.

Previous studies did not identify any major safety issues with DEX. Some patients might experience changes in heart rate or blood pressure, but these are usually manageable with other medications.

Hospitals already use DEX to keep patients calm and sleepy, so doctors are very familiar with it. Overall, DEX appears well-tolerated and safe for many patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for postoperative cognitive dysfunction use standard sedation protocols, which vary widely. But dexmedetomidine hydrochloride works differently. It's an alpha-2 adrenergic agonist that provides sedation with less risk of respiratory depression, which is a common side effect of other sedatives. Researchers are excited about dexmedetomidine because it might offer a safer sedation option, helping patients recover their cognitive function more effectively after surgery.

What evidence suggests that Dexmedetomidine might be an effective treatment for postoperative cognitive dysfunction?

Research has shown that dexmedetomidine (DEX) can help manage memory and thinking problems after surgery, known as postoperative cognitive dysfunction (POCD). One study found that the incidence of POCD decreased from 21.31% to 9.2% with the use of DEX. Other studies have reported similar findings, suggesting that DEX helps protect the brain after surgery. A review of multiple studies also supports this, indicating a lower risk of POCD in older adults using DEX. In this trial, participants in the Dexmedetomidine Hydrochloride Group will receive DEX, while those in the Standard of Care Group will follow standard sedation protocols. Overall, the evidence suggests that DEX can improve recovery after surgery by protecting against cognitive issues. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephen Choi, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for cardiac surgery patients aged 60 or older who are recovering in the CVICU and can complete cognitive tests post-surgery. It's not for those with major pre-op cognitive issues, certain heart conditions, severe liver or kidney disease, or an allergy to dexmedetomidine.

Inclusion Criteria

I am scheduled for heart surgery that requires opening my chest, with initial recovery in the CVICU.

I am 60 years old or older.

Exclusion Criteria

I do not have severe allergies or conditions that dexmedetomidine could worsen.

Pre-operative major cognitive dysfunction (CogState Brief Battery score < 80)

I have had an aortic arch replacement or Bentall procedure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexmedetomidine or standard sedation protocols post-surgery

Up to 12 hours

In-hospital stay

In-hospital Monitoring

Participants are monitored for delirium, hemodynamic stability, and other complications

10 days

Daily assessments

Follow-up

Participants are monitored for cognitive outcomes and other post-operative conditions

12 months

Assessments at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine Hydrochloride

Trial Overview

The study is testing whether Dexmedetomidine (DEX) can prevent long-term memory and thinking problems after cardiac surgery. The goal is to see if DEX improves recovery and reduces hospital stay and healthcare costs.

How Is the Trial Designed?

Group I: Dexmedetomidine Hydrochloride Group Active Control 1 Intervention

Patients will receive a loading dose of 1.2 μg/kg dexmedetomidine prior to transfer to CVICU over 20-60 min immediately postoperative, followed by continuous infusion of 0.3 μg/kg/h for up to 12 hours or until patient is ready for discharge from CVICU (whichever is earlier). Any additional sedatives necessary at the discretion of ICU.

Group II: Standard of Care Group Active Control 1 Intervention

Standard sedation protocols will be followed at the discretion of the attending physician.

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?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Brain Canada

Collaborator

Trials

22

Recruited

6,100+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

University of Saskatchewan

Collaborator

Trials

261

Recruited

156,000+

The Dana Foundation

Collaborator

Trials

18

Recruited

980+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Fraser Health

Collaborator

Trials

49

Recruited

708,000+

Providence Health & Services

Collaborator

Trials

131

Recruited

827,000+

London Health Sciences Centre

Collaborator

Trials

151

Recruited

60,400+

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 significantly reduces the incidence of postoperative cognitive dysfunction (POCD) in elderly adults after general anesthesia, with a relative risk of 0.59 based on 13 randomized controlled trials.

The use of dexmedetomidine also improves cognitive function as measured by the Mini-Mental State Examination (MMSE) score on the first postoperative day, indicating its potential benefits in enhancing recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients after general anaesthesia: A meta-analysis. Zhou, C., Zhu, Y., Liu, Z., et al.[2022]

Dexmedetomidine hydrochloride (Dex) significantly lowers heart rate and arterial pressure during and after intracranial aneurysm surgery, indicating its effectiveness in stabilizing hemodynamics.

Patients receiving Dex showed improved cognitive protection and reduced postoperative pain compared to the control group, suggesting its beneficial role in recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain protective effect and hemodynamics of dexmedetomidine hydrochloride in patients with intracranial aneurysm. Zheng, D., Zhao, S., Zhang, N., et al.[2020]

In a study of 80 elderly patients undergoing laparoscopic colorectal surgery, dexmedetomidine at doses of 0.5 and 0.8 µg/kg significantly reduced the incidence of postoperative cognitive dysfunction (POCD) compared to lower doses and a control group.

While higher doses of dexmedetomidine were effective in reducing POCD, they were also associated with increased rates of hypotension and bradycardia, particularly in the highest dose group, indicating a need for careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of different doses of dexmedetomidine on cognitive dysfunction in elderly patients early after laparoscopic surgery for colorectal cancer]. Zhang, Y., Xing, Z., Xu, Y., et al.[2018]

In elderly patients undergoing major surgery, continuous infusion of dexmedetomidine (DEX) at doses of 200 μg or 400 μg significantly reduced the incidence of postoperative delirium (POD) and early postoperative cognitive dysfunction (POCD) compared to lower doses.

DEX 400 μg was particularly effective in reducing early POCD in patients who had open surgery, and this treatment did not lead to increased sedation, pain intensity, or side effects, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial. Zhao, W., Hu, Y., Chen, H., et al.[2022]

In a study of 148 aged surgical patients, dexmedetomidine significantly reduced the incidence of post-operative cognitive dysfunction (POCD) to 9.20% compared to 21.31% in the control group, indicating its efficacy in protecting cognitive function after surgery.

The mechanism behind this protective effect may involve the suppression of inflammatory markers, as dexmedetomidine inhibited the post-operative increase of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), which were positively correlated with the incidence of POCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of dexmedetomidine on post-operative cognitive dysfunction and inflammatory factors in senile patients. Chen, W., Liu, B., Zhang, F., et al.[2022]

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]

A meta-analysis of 14 randomized controlled trials involving 1626 elderly adults showed that dexmedetomidine significantly reduces the incidence of postoperative cognitive dysfunction (POCD), with a risk ratio of 0.47, indicating nearly a 53% reduction in risk.

The most robust evidence for dexmedetomidine's effectiveness in preventing POCD came from studies using the Mini-Mental State Examination (MMSE) for diagnosis, suggesting it may be a valuable preventative treatment for cognitive issues after surgery in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of dexmedetomidine on postoperative cognitive dysfunction in the elderly: A meta-analysis of randomized controlled trials. Yu, H., Kang, H., Fan, J., et al.[2022]

In a study of 83 pediatric patients undergoing inguinal hernia repair, intranasal administration of dexmedetomidine resulted in lower rates of emergence agitation (4.76%) compared to intravenous administration (21.95%), indicating a more favorable awakening experience.

Patients receiving intranasal dexmedetomidine also showed better cognitive, language, and motor scores three days post-surgery, with a significantly lower incidence of cognitive dysfunction (4.76% vs. 21.95% for IV), suggesting that this route of administration may enhance early cognitive recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of different routes of administration on early cognitive function following inguinal hernia repair. Huang, J., Deng, B., Shuai, J., et al.[2021]

Citations

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The results of this study showed that dexmedetomidine could effectively manage POCD in elderly patients with fracture.

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In conclusion, this meta-analysis suggests that DEX has a protective effect on the cognitive function of patients with GICs undergoing RS. Integrating DEX into ...

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A meta-analysis by Yu et al (6) indicated that DEX was associated with a reduced risk of POCD in old adults. Therefore, it was hypothesized that ...

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In hospital outcomes include delirium (assessed twice daily post-operative day (POD) 0-10, death, hemodynamic instability requiring vasopressors, time to ...

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However, few studies have demonstrated the safety and efficacy of PCA-based DEX in reducing postoperative cognitive decline. This study is the first to ...

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Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that ...

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The Effects of Dexmedetomidine on Perioperative...

Dexmedetomidine (DEX) effectively reduces delirium in the intensive care unit and reportedly attenuates cognitive decline following major noncardiac surgery.