Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients

NCT ID: NCT04289142

Last Updated: 2025-12-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

2400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-01

Study Completion Date

2029-03-31

Brief Summary

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Anesthesia is a drug induced, reversible, comatose state that facilitates surgery and it is widely assumed that cognition returns to baseline after anesthetics have been eliminated. However, many patients have persistent memory impairment for weeks to months after surgery. Cardiac surgery appears to carry the highest risk of postoperative cognitive dysfunction (POCD). These cognitive deficits are associated with increased mortality, prolonged hospital stay and loss of independence. The investigators propose to investigate the role of Dexmedetomidine (DEX) in preventing long-term POCD after cardiac surgery and enhancing early postoperative recovery. It is anticipated that DEX will be the first effective preventative therapy for POCD, improve patient outcomes, and reduce length of stay and healthcare costs.

Detailed Description

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Dexmedetomidine (DEX), a highly potent and selective α2-adrenoceptors (α2R) agonist used in clinical practice for sedation, analgesia, and anxiolysis, was recently shown to have beneficial effects on early cognitive changes by reducing delirium in humans. It also reduced memory impairment after surgery and isoflurane anesthesia, both in elderly mice (20-22 months) and in pups exposed to anesthesia in the early postnatal period. Importantly, co-treatment with DEX has been shown to restore learning and memory function in rats exposed to propofol in utero. Therefore, the investigators set out to investigate whether DEX has an effect on cognitive dysfunction months after surgery and whether it accelerates cognitive recovery from anesthesia and surgery.

This is a double blinded, multi-site trial facilitated by Clinical Trials Ontario (CTO). Participants will be randomized 1:1 in permuted blocks of 4 to 8. The randomization sequence will be computer generated and stratified by 2 factors, planned procedure (CABG/CABG + valve or valve only procedure) and study site.

In hospital outcomes include delirium (assessed twice daily post-operative day (POD) 0-10, death, hemodynamic instability requiring vasopressors, time to extubation, re-intubation (and reason), length of stay (in Cardiovascular Intensive Care Unit and total hospital), POCD, depressive symptoms between POD 4-10, post-operative complications (infection \[surgical site, sepsis, pneumonia\], myocardial infarction, renal replacement therapy, re-operation, cumulative opioid consumption (to POD 5), in-hospital mortality.

Post-operative outcomes include POCD (3/6/12 months), depression (3/6/12 months), mild cognitive impairment (MCI) at 3/6/12 months (defined as 1-2 standard deviations below age matched controls), persistent surgical site pain at sternotomy/thoracotomy/graft harvest site (Brief Pain Inventory, 3/6/12 months), recovery (3,6, 12 months).

Conditions

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Dexmedetomidine Hypnotics and Sedatives Central Nervous System Depressants Delirium Cognitive Dysfunction Cognition Disorder Neurocognitive Disorders Mental Disorders Confusion Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Signs and Symptoms Physiological Effects of Drugs Analgesics, Non-Narcotic Analgesics Molecular Mechanisms of Pharmacological Action

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dexmedetomidine Hydrochloride Group

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 Type ACTIVE_COMPARATOR

Dexmedetomidine Hydrochloride Group

Intervention Type DRUG

Dexmedetomidine will be initiated prior to transfer to the CVICU with loading dose of 1.2 ug/kg over approximately 20-60 minutes. This will be followed by an infusion at 0.3 ug/kg/h in CVICU for up to 12 hours from the time DEX infusion started or until the patient is ready for discharge from the CVICU (whichever is earlier). Any additional sedatives necessary at the discretion of ICU.

Standard of Care Group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Dexmedetomidine Hydrochloride Group

Dexmedetomidine will be initiated prior to transfer to the CVICU with loading dose of 1.2 ug/kg over approximately 20-60 minutes. This will be followed by an infusion at 0.3 ug/kg/h in CVICU for up to 12 hours from the time DEX infusion started or until the patient is ready for discharge from the CVICU (whichever is earlier). Any additional sedatives necessary at the discretion of ICU.

Intervention Type DRUG

Other Intervention Names

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Dexmedetomidine Hydrochloride

Eligibility Criteria

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Inclusion Criteria

* Planned CABG (+/- valve, including off-pump) or valve replacement via sternotomy/thoracotomy, with initial recovery in the Cardiovascular Intensive Care Unit (CVICU)
* Age ≥60

Exclusion Criteria

* Lack of patient consent
* Pre-operative major cognitive dysfunction (CogState Brief Battery score \< 80) at screening
* Aortic arch replacement/re-implantation (surgery requiring hypothermic circulatory arrest, e.g. Bentall procedure)
* Allergy/contraindication to dexmedetomidine (untreated 2nd degree type 2 or 3rd degree heart block (pacemaker), cirrhosis, HR \< 50 , grade 4 LV, renal failure or on renal replacement therapy)
* Unlikely to comply with study assessments (e.g. no fixed address, cannot complete cognitive tests at the 3, 6, and 12 month time points)
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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London Health Sciences Centre

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role collaborator

McMaster University

OTHER

Sponsor Role collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

The Dana Foundation

OTHER

Sponsor Role collaborator

Brain Canada

OTHER

Sponsor Role collaborator

Alzheimer's Association

OTHER

Sponsor Role collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role collaborator

University of Saskatchewan

OTHER

Sponsor Role collaborator

Fraser Health

OTHER

Sponsor Role collaborator

Providence Health & Services

OTHER

Sponsor Role collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen Choi, MD,MSc,FRCPC

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

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Royal Columbian Hospital

Vancouver, British Columbia, Canada

Site Status ACTIVE_NOT_RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

London Health Sciences

London, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Toronto General Hospital

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Laval University

Québec, Quebec, Canada

Site Status RECRUITING

University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status ACTIVE_NOT_RECRUITING

Countries

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Canada

Central Contacts

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Stephen Choi, MD,MSc,FRCPC

Role: CONTACT

416-480-6100 ext. 1711

Lilia Kaustov, PhD

Role: CONTACT

416-480-6100 ext. 89607

Facility Contacts

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Nicola Edwards

Role: primary

Lilia Kaustov, PhD

Role: primary

416-480-6100 ext. 89607

Sanjay Yagnik

Role: primary

Francois Laforge

Role: primary

References

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Choi S, Jerath A, Jones P, Avramescu S, Djaiani G, Syed S, Saha T, Kaustov L, Kiss A, D'Aragon F, Hedlin P, Rajamohan R, Couture EJ, Singh A, Mapplebeck JC, Wong S, Orser BA. Cognitive Outcomes after DEXmedetomidine sedation in cardiac surgery: CODEX randomised controlled trial protocol. BMJ Open. 2021 Apr 13;11(4):e046851. doi: 10.1136/bmjopen-2020-046851.

Reference Type DERIVED
PMID: 33849856 (View on PubMed)

Other Identifiers

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1743

Identifier Type: -

Identifier Source: org_study_id

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