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Dexmedetomidine to Reduce the Incidence of POCD After Open Cardiac Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03480061
Recruitment Status : Active, not recruiting
First Posted : March 27, 2018
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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 disease Intervention/treatment Phase
Delirium Postoperative Cognitive Dysfunction Dexmedetomidine Cognitive Impairment Depression 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).

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 9, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/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 Name: Dexmedetomidine Hydrochloride

No Intervention: Standard of Care Group
Standard sedation protocols will be followed at the discretion of the attending physician.



Primary Outcome Measures :
  1. Rate of recruitment [ Time Frame: 12 Months ]
    Ability to recruit 15% a full trail sample size (90 participants)


Secondary Outcome Measures :
  1. Completion of follow-up assessments [ Time Frame: 3 months ]
    Ability to achieve 90% follow-up of administering cognitive assessment 3 months after surgery



Information from the National Library of Medicine

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

Information from the National Library of Medicine

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): NCT03480061


Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
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Principal Investigator: Stephen Choi, MD,MSc,FRCPC Sunnybrook Health Sciences Centre
Principal Investigator: Sinziana Avramescu, MD,PhD,FRCPC Sunnybrook Health Sciences Centre
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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03480061    
Other Study ID Numbers: 2018
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Delirium
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action