We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients (CODEX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04289142
Recruitment Status : Recruiting
First Posted : February 28, 2020
Last Update Posted : March 15, 2022
Sponsor:
Collaborators:
London Health Sciences Centre
University Health Network, Toronto
McMaster University
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Delirium Cognitive Dysfunction Cognition Disorder Neurocognitive Disorders Mental Disorders Confusion Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Signs and Symptoms Dexmedetomidine Hypnotics and Sedatives Central Nervous System Depressants Physiological Effects of Drugs Analgesics, Non-Narcotic Analgesics Molecular Mechanisms of Pharmacological Action Drug: Dexmedetomidine Hydrochloride Group Phase 4

Detailed Description:

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 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).

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients: CODEX Trial
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : March 2026
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Dexmedetomidine Hydrochloride Group
Patients will receive a loading dose of 1.2 μg/kg dexmedetomidine prior to transfer to CVICU over 20 min immediately postoperative, followed by continuous infusion of 0.1- 1.2 μg/kg/h for up to 24 hours or until patient is ready for discharge from CVICU (whichever is earlier).
 Drug: Dexmedetomidine Hydrochloride Group
Dexmedetomidine will be initiated prior to transfer to the CVICU with loading dose of 1.2 ug kg-1 over approximately 20 minutes. This will be followed by an infusion at 0.1-1.2 ug kg-1h-1 in CVICU for up to 24 hours from the time DEX infusion started or until the patient is ready for discharge from the CVICU (whichever is earlier).
Other Name: Dexmedetomidine Hydrochloride
No Intervention: Standard of Care Group
Standard sedation protocols will be followed at the discretion of the attending physician.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Post-operative cognitive dysfunction [ Time Frame: 3 months ]
    Presence of POCD assessed by CogState Brief Battery (CBB)


Secondary Outcome Measures :
  1. Post-operative cognitive dysfunction (POCD) at 1 week, 6 months, 12 months after surgery [ Time Frame: 1 week, 6 and 12 months ]
    POCD assessed by CogState Brief Battery (CBB)

  2. Delirium [ Time Frame: Anytime up to post-operative day 10 ]
    Confusion Assessment Method (CAM/CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC), binary scale to determine if delirium is present or absent

  3. Length of stay [ Time Frame: An average of 5 -14 days ]
    ICU and total hospital stay

  4. Depressive symptoms [ Time Frame: 3, 6, and 12 months ]
    Evaluated by PHQ-9 (Patient Health Questionnaire, scale 0-27, higher score is worse outcome)

  5. Persistent Surgical Site Pain [ Time Frame: 3, 6, and 12 months ]
    Evaluated by Brief Pain Inventory

  6. Quality of Surgical Recovery [ Time Frame: 3, 6, 12 months ]
    Evaluated by QoR- (Quality of Recovery) 40 questionnaire (scale: 0-200, higher is better outcome)

  7. Mild Cognitive Impairment [ Time Frame: 3, 6, and 12 months ]
    Presence of MCI assessed by CogState Brief Battery (CBB)

  8. In-hospital mortality for index surgery [ Time Frame: through initial inpatient admission, average of 1 week ]
    death before hospital discharge after surgery

  9. Opioid consumption to POD 4 [ Time Frame: 4 days ]
    Cumulative opioid consumption

  10. Time to extubation [ Time Frame: through ICU stay, average of 12 hours ]
    Time from ICU arrival to cessation of mechanical ventilation


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  • Aortic arch replacement/re-implantation (Bentalls)
  • 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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04289142


Contacts
Layout table for location contacts
Contact: Stephen Choi, MD,MSc,FRCPC 416-480-6100 ext 1711 stephen.choi@sunnybrook.ca
Contact: Lilia Kaustov, PhD 416-480-6100 ext 89607 lilia.kaustov@sunnybrook.ca

Locations
Layout table for location information
Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Lilia Kaustov, PhD    416-480-6100 ext 89607    lilia.kaustov@sunnybrook.ca   
Principal Investigator: Stephen Choi, MD,FRCPC,MSc         
Principal Investigator: Sinziana Avramescu, MD,FRCPC,PhD         
Sub-Investigator: Angela Jerath, MD,FRCPC         
Sub-Investigator: George Djaiani, MD,FRCPC         
Sub-Investigator: Philip Jones, MD,FRCPC         
Sub-Investigator: Summer Syed, MD,FRCPC,MSc         
Sub-Investigator: David Mazer, MD,FRCPC,PhD         
Sub-Investigator: Tarit Saha, MD,FRCPC         
Sub-Investigator: Beverley A Orser, MD,PhD,FRCPC         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
London Health Sciences Centre
University Health Network, Toronto
McMaster University
Investigators
Layout table for investigator information
Principal Investigator: Stephen Choi, MD,MSc,FRCPC Sunnybrook Health Sciences Centre
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04289142    
Other Study ID Numbers: 1743
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: March 15, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All de-identified participants data collected during this trial that underlie the results reported in the publication(s) will be available upon request after publication of the primary results.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be available upon request immediately after publication of the primary results. No end date.
Access Criteria: Direct request to PI. Anyone who wishes to access the data.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Nervous System Diseases
Confusion
Neurologic Manifestations
Neurobehavioral Manifestations
Disease
Cognitive Dysfunction
Mental Disorders
Neurocognitive Disorders
Cognition Disorders
Pathologic Processes
Dexmedetomidine
Hypnotics and Sedatives
 Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action