Dexmedetomidine to Reduce the Incidence of POCD After Open Cardiac Surgery

NCT ID: NCT03480061

Last Updated: 2024-12-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-09
• Study Completion Date: 2026-12-31

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.

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.

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 (for full multicentre trial).

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 4), 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; Postoperative Cognitive Dysfunction; Dexmedetomidine; Cognitive Impairment; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Dexmedetomidine Hydrochloride Group

Patients will receive a loading dose of 1 μg/kg dexmedetomidine prior to transfer to CVICU over 20 min immediately postoperative, followed by continuous infusion of 0.1- 1.0 μg/kg/h for up to 24 hours or until patient is ready for discharge from CVICU (whichever is earlier).

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine Hydrochloride Group

Intervention Type: DRUG

Dexmedetomidine will be initiated prior to transfer to the CVICU with loading dose of 1 ug kg-1 over approximately 20 minutes. This will be followed by an infusion at 0.1-1.0 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).

Standard of Care Group

Standard sedation protocols will be followed at the discretion of the attending physician.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dexmedetomidine Hydrochloride Group

Dexmedetomidine will be initiated prior to transfer to the CVICU with loading dose of 1 ug kg-1 over approximately 20 minutes. This will be followed by an infusion at 0.1-1.0 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).

Intervention Type: DRUG

Other Intervention Names

Dexmedetomidine Hydrochloride

Eligibility Criteria

Inclusion Criteria

• Planned CABG (including off-pump) or valve replacement (+/- CABG) via sternotomy/thoracotomy, with initial recovery in the Cardiovascular Intensive Care Unit (CVICU)
• age ≥60

Exclusion Criteria

• Lack of patient consent
• Pregnant or nursing females
• 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 timepoints)

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Choi, MD,MSc,FRCPC

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Sinziana Avramescu, MD,PhD,FRCPC

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

2018

Identifier Type: -

Identifier Source: org_study_id