Dexmedetomidine to Reduce the Incidence of POCD After Open Cardiac Surgery

Sponsor
Sunnybrook Health Sciences Centre (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03480061
Collaborator
(none)
90
Enrollment
1
Location
2
Arms
51.7
Anticipated Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Dexmedetomidine Hydrochloride Group
Phase 4

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Dexmedetomidine to Reduce the Incidence of Persistent Cognitive Dysfunction After Open Cardiac Surgery: A Pilot Randomized Trial
Actual Study Start Date :
Aug 9, 2018
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: 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).

Drug: 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).
Other Names:
  • Dexmedetomidine Hydrochloride
  • No Intervention: Standard of Care Group

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

    Outcome Measures

    Primary Outcome Measures

    1. Rate of recruitment [12 Months]

      Ability to recruit 15% a full trail sample size (90 participants)

    Secondary Outcome Measures

    1. Completion of follow-up assessments [3 months]

      Ability to achieve 90% follow-up of administering cognitive assessment 3 months after surgery

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Sunnybrook Health Sciences CentreTorontoOntarioCanadaM4N 3M5

    Sponsors and Collaborators

    • Sunnybrook Health Sciences Centre

    Investigators

    • Principal Investigator: Stephen Choi, MD,MSc,FRCPC, Sunnybrook Health Sciences Centre
    • Principal Investigator: Sinziana Avramescu, MD,PhD,FRCPC, Sunnybrook Health Sciences Centre

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sunnybrook Health Sciences Centre
    ClinicalTrials.gov Identifier:
    NCT03480061
    Other Study ID Numbers:
    • 2018
    First Posted:
    Mar 27, 2018
    Last Update Posted:
    Oct 7, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 7, 2021