DeliriumPhase 4CODEXNCT04289142
Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients
A Phase 4 study testing Dexmedetomidine Hydrochloride Group in people with Delirium and Cognitive Dysfunction, run by Sunnybrook Health Sciences Centre at 8 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Delirium, Cognitive Dysfunction, Cognition Disorder
- What is being tested?
- Dexmedetomidine Hydrochloride Group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,400 participants
- Where
- 8 sitesCanada
- Study dates
- 1 Dec 2019to Mar 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Planned CABG (+/- valve, including off-pump) or valve replacement via sternotomy/thoracotomy, with initial recovery in the Cardiovascular Intensive Care Unit (CVICU)
- Age ≥60
Who cannot join
- 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)
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Canada8 sites, 4 recruiting
- Active, not recruiting
London Health Sciences
London, Ontario, N6A 5A5
- Recruiting
Laval University
Québec, Quebec, G1V 0A6
Francois Laforge, francois.laforge.1@ulaval.ca
Etienne Couture
- Active, not recruiting
University of Saskatchewan
Saskatoon, Saskatchewan, S7N 0W8
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Lilia Kaustov, PhD, 416-480-6100 ext. 89607, lilia.kaustov@sunnybrook.ca
Stephen Choi, MD,FRCPC,MSc
- Not yet recruiting
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Sanjay Yagnik, Sanjay.Yagnik@unityhealth.to
David Mazer
- Active, not recruiting
Toronto General Hospital
Toronto, Ontario, M5G 2C4
- Active, not recruiting
Royal Columbian Hospital
Vancouver, British Columbia, V3L 0A2
- Recruiting
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Nicola Edwards, nedwards@providencehealth.bc.ca
Raja Rajamohan, M.D
About this study
Official title: Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients: CODEX Trial
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.
Read the 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 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
- Delirium, Cognitive Dysfunction, Cognition Disorder, Neurocognitive Disorders, Mental Disorders, Confusion
- Being tested
- Dexmedetomidine Hydrochloride Group
- Medical subject headings
- Delirium, Cognitive Dysfunction, Cognition Disorders, Neurocognitive Disorders, Mental Disorders, Confusion, Neurobehavioral Manifestations, Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexmedetomidine Hydrochloride GroupDrug
Also called Dexmedetomidine Hydrochloride
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.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine Hydrochloride Group | Active comparator | 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. Receives: Drug: Dexmedetomidine Hydrochloride Group |
| Standard of Care Group | No intervention | Standard sedation protocols will be followed at the discretion of the attending physician. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-operative cognitive dysfunction
Presence of POCD assessed by CogState Brief Battery (CBB)
Measured: 3 months
Secondary outcomes (10)
Post-operative cognitive dysfunction (POCD) at 1 week, 6 months, 12 months after surgery
POCD assessed by CogState Brief Battery (CBB)
Measured: 1 week, 6 and 12 months
Delirium
Confusion Assessment Method (CAM/CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC), binary scale to determine if delirium is present or absent
Measured: Anytime up to post-operative day 10
Length of stay
ICU and total hospital stay
Measured: An average of 5 -14 days
Depressive symptoms
Evaluated by PHQ-9 (Patient Health Questionnaire, scale 0-27, higher score is worse outcome)
Measured: 3, 6, and 12 months
Persistent Surgical Site Pain
Evaluated by Brief Pain Inventory
Measured: 3, 6, and 12 months
Quality of Surgical Recovery
Evaluated by QoR- (Quality of Recovery) 40 questionnaire (scale: 0-200, higher is better outcome)
Measured: 3, 6, 12 months
Mild Cognitive Impairment
Presence of MCI assessed by CogState Brief Battery (CBB)
Measured: 3, 6, and 12 months
In-hospital mortality for index surgery
death before hospital discharge after surgery
Measured: through initial inpatient admission, average of 1 week
Opioid consumption to POD 4
Cumulative opioid consumption
Measured: 4 days
Time to extubation
Time from ICU arrival to cessation of mechanical ventilation
Measured: through ICU stay, average of 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2020
- Study start1 Dec 2019
- Primary completionJul 2028 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- London Health Sciences Centre, University Health Network, Toronto, McMaster University, Canadian Institutes of Health Research (CIHR), The Dana Foundation, Brain Canada, Alzheimer's Association, Hamilton Health Sciences Corporation, University of Saskatchewan, Fraser Health, Providence Health & Services
- Responsible party
- Sponsor
- Investigators
- Stephen Choi, MD,MSc,FRCPC, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04289142
- Sponsor's protocol ID
- 1743
- Acronym
- CODEX
- Status last verified
- Jul 2025
- First submitted
- 9 Oct 2019
- Last updated
- 1 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 33849856