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Recruiting NCT04289142

Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients

Phase IV Interventional Delirium Cognitive Dysfunction Cognition Disorder Neurocognitive Disorders

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Dexmedetomidine Hydrochloride Group.
Who it may be relevant to
Registry conditions: Delirium, Cognitive Dysfunction, Cognition Disorder, Neurocognitive Disorders. Basic parameters: from 60 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients: CODEX Trial

Overview

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

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).

Interventions

  • Drug 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.

Primary outcome measures

  • Post-operative cognitive dysfunction [Time frame: 3 months]
Secondary outcome measures (10)
  • Post-operative cognitive dysfunction (POCD) at 1 week, 6 months, 12 months after surgery [Time frame: 1 week, 6 and 12 months]
  • Delirium [Time frame: Anytime up to post-operative day 10]
  • Length of stay [Time frame: An average of 5 -14 days]
  • Depressive symptoms [Time frame: 3, 6, and 12 months]
  • Persistent Surgical Site Pain [Time frame: 3, 6, and 12 months]
  • Quality of Surgical Recovery [Time frame: 3, 6, 12 months]
  • Mild Cognitive Impairment [Time frame: 3, 6, and 12 months]
  • In-hospital mortality for index surgery [Time frame: through initial inpatient admission, average of 1 week]
  • Opioid consumption to POD 4 [Time frame: 4 days]
  • Time to extubation [Time frame: through ICU stay, average of 12 hours]

Eligibility 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) 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Prevention

Study locations

Canada · 8 centers
  • Royal Columbian Hospital — Vancouver
  • St. Paul's Hospital — Vancouver
  • London Health Sciences — London
  • Sunnybrook Health Sciences Centre — Toronto
  • St. Michael's Hospital — Toronto
  • Toronto General Hospital — Toronto
  • Laval University — Québec
  • University of Saskatchewan — Saskatoon

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. PMID 33849856

Identifiers

NCT: NCT04289142 · 1743

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗