Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients (CODEX)
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|ClinicalTrials.gov Identifier: NCT04289142|
Recruitment Status : Recruiting
First Posted : February 28, 2020
Last Update Posted : October 19, 2020
|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|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2400 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|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|
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.
- Post-operative cognitive dysfunction [ Time Frame: 3 months ]Presence of POCD assessed by CogState Brief Battery (CBB)
- 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)
- 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
- Length of stay [ Time Frame: An average of 5 -14 days ]ICU and total hospital stay
- Depressive symptoms [ Time Frame: 3, 6, and 12 months ]Evaluated by PHQ-9 (Patient Health Questionnaire, scale 0-27, higher score is worse outcome)
- Persistent Surgical Site Pain [ Time Frame: 3, 6, and 12 months ]Evaluated by Brief Pain Inventory
- 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)
- Mild Cognitive Impairment [ Time Frame: 3, 6, and 12 months ]Presence of MCI assessed by CogState Brief Battery (CBB)
- In-hospital mortality for index surgery [ Time Frame: through initial inpatient admission, average of 1 week ]death before hospital discharge after surgery
- Opioid consumption to POD 4 [ Time Frame: 4 days ]Cumulative opioid consumption
- Time to extubation [ Time Frame: through ICU stay, average of 12 hours ]Time from ICU arrival to cessation of mechanical ventilation
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
|Contact: Stephen Choi, MD,MSc,FRCPC||416-480-6100 ext firstname.lastname@example.org|
|Contact: Lilia Kaustov, PhD||416-480-6100 ext email@example.com|
|Sunnybrook Health Sciences Centre||Recruiting|
|Toronto, Ontario, Canada, M4N 3M5|
|Contact: Lilia Kaustov, PhD 416-480-6100 ext 89607 firstname.lastname@example.org|
|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|
|Principal Investigator:||Stephen Choi, MD,MSc,FRCPC||Sunnybrook Health Sciences Centre|