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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04289142
Other study ID # 1743
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date December 1, 2019
Est. completion date March 2026

Study information

Verified date November 2023
Source Sunnybrook Health Sciences Centre
Contact Stephen Choi, MD,MSc,FRCPC
Phone 416-480-6100
Email stephen.choi@sunnybrook.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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).


Recruitment information / eligibility

Status Recruiting
Enrollment 2400
Est. completion date March 2026
Est. primary completion date March 2026
Accepts healthy volunteers No
Gender All
Age group 60 Years and older
Eligibility 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)

Study Design


Intervention

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 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.

Locations

Country Name City State
Canada Sunnybrook Health Sciences Centre Toronto Ontario

Sponsors (4)

Lead Sponsor Collaborator
Sunnybrook Health Sciences Centre London Health Sciences Centre, McMaster University, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Post-operative cognitive dysfunction Presence of POCD assessed by CogState Brief Battery (CBB) 3 months
Secondary Post-operative cognitive dysfunction (POCD) at 1 week, 6 months, 12 months after surgery POCD assessed by CogState Brief Battery (CBB) 1 week, 6 and 12 months
Secondary Delirium Confusion Assessment Method (CAM/CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC), binary scale to determine if delirium is present or absent Anytime up to post-operative day 10
Secondary Length of stay ICU and total hospital stay An average of 5 -14 days
Secondary Depressive symptoms Evaluated by PHQ-9 (Patient Health Questionnaire, scale 0-27, higher score is worse outcome) 3, 6, and 12 months
Secondary Persistent Surgical Site Pain Evaluated by Brief Pain Inventory 3, 6, and 12 months
Secondary Quality of Surgical Recovery Evaluated by QoR- (Quality of Recovery) 40 questionnaire (scale: 0-200, higher is better outcome) 3, 6, 12 months
Secondary Mild Cognitive Impairment Presence of MCI assessed by CogState Brief Battery (CBB) 3, 6, and 12 months
Secondary In-hospital mortality for index surgery death before hospital discharge after surgery through initial inpatient admission, average of 1 week
Secondary Opioid consumption to POD 4 Cumulative opioid consumption 4 days
Secondary Time to extubation Time from ICU arrival to cessation of mechanical ventilation through ICU stay, average of 12 hours
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