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Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03928236
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : May 13, 2020
Information provided by (Responsible Party):
Population Health Research Institute

Brief Summary:
B-FREE is a pragmatic, multicentre, cluster crossover trial evaluating whether a policy limiting the use of intra-operative benzodiazepine reduces post-operative delirium when compared with a policy of 'ad libitum' administration. The knowledge generated by this study will provide the basis for cardiac anesthesia practice guidelines.

Condition or disease Intervention/treatment Phase
Delirium Post-cardiac Surgery Other: Limited Intraoperative Benzodiazepine Other: Liberal Intraoperative Benzodiazepine Not Applicable

Detailed Description:

Delirium, an acute state of confusion, occurs in approximately 1 in 5 adults after open heart surgery. Even though it is a temporary state, patients who experience delirium are at increased risk of serious problems that last after the delirium has resolved. These problems include decreases in thinking, mobility, self-care, and the ability to live independently in a community setting. Patients who experience delirium have longer stays in hospital, are more likely to be discharged to a nursing home, and are more likely to die. Benzodiazepines are a sedative and amnestic medication that may be associated with delirium. As such, benzodiazepines are rarely used for sedation in the intensive care unit after cardiac surgery. However, benzodiazepines continue to be used frequently in the operating room by anesthesiologists during open heart surgery because of their amnestic effects and limited impact on blood pressure. Nevertheless, practice is divided among cardiac anesthesiologists, with some never using benzodiazepines and others using them for nearly all patients.

Because the best approach (routine benzodiazepines or restricted benzodiazepines) remains uncertain, we will compare the effect of a hospital policy of intraoperative medication use that includes benzodiazepines to a policy that uses alternative medications and no benzodiazepines on the incidence of delirium after open heart surgery. The findings of the study have the potential to improve the outcomes of tens of thousands of patients around the world and will provide the basis for cardiac anesthesiology practice guidelines.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15886 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Multicenter, cluster-randomized, crossover trial
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Arm Intervention/treatment
Experimental: Limited Benzodiazepine Policy
Policy of no routine use of any intraoperative benzodiazepines.
Other: Limited Intraoperative Benzodiazepine
policy for limited use of intraoperative benzodiazepine

Active Comparator: Liberal Benzodiazepine Policy
Policy for the administration of benzodiazepine as per clinical guidelines but no lower than 0.03 mg/kg (ideal body weight midazolam equivalent) to all patients undergoing cardiac surgery. Any benzodiazepine may be used.
Other: Liberal Intraoperative Benzodiazepine
policy for liberal use of intraoperative benzodiazepine

Primary Outcome Measures :
  1. Incidence of Delirium [ Time Frame: up to 72 hours post cardiac surgery ]
    Delirium assessed in the ICU using standardized and validated delirium scales

Secondary Outcome Measures :
  1. Number of Days in ICU after Cardiac Surgery [ Time Frame: through study completion, approximately 22 months ]
    Length of Stay (LOS) in Intensive Care Unit after Cardiac Surgery

  2. Number of Days in Hospital after Cardiac Surgery [ Time Frame: through study completion, approximately 22 months ]
    Length of Stay (LOS) in Hospital after Cardiac Surgery

  3. Incidence of In-hospital Mortality [ Time Frame: through study completion, approximately 22 months ]
    Death from any cause after index cardiac surgery and during the index hospitalization

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Hospital is a major surgical center with a minimum of 500 cases of cardiac surgery per year.
  • Equipoise by the hospital physicians regarding the use of benzodiazepines during surgery (≥ 95% of hospital cardiac anesthesia group agrees to manage adult patients (age >18 years) as per the benzodiazepine policy in place during a given crossover period).
  • Hospital routinely assesses patients (age >18 years) for postoperative delirium at least once every 12 hours during the initial 72 hours after cardiac surgery as a part of routine clinical care using either the Confusion Assessment Method-ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC).

Exclusion Criteria:

- Hospital does not meet inclusion criteria

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 identifier (NCT number): NCT03928236

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Contact: B-Free Study Coordinator 905212100

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Canada, Ontario
Hamilton Health Sciences, General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Principal Investigator, MD         
Sponsors and Collaborators
Population Health Research Institute
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Principal Investigator: Jessica Spence, MD FRCPC Population Health Research Institute
Principal Investigator: Eric Jacobsohn, MBChB MPHE University of Manitoba
Study Chair: Stuart Connolly, MD FRCPC Population Health Research Institute
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Responsible Party: Population Health Research Institute Identifier: NCT03928236    
Other Study ID Numbers: B-Free.2019
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 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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Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders