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Trial record 1 of 1 for:    NCT02546765
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Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery (DEXACET)

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ClinicalTrials.gov Identifier: NCT02546765
Recruitment Status : Completed
First Posted : September 11, 2015
Results First Posted : January 7, 2020
Last Update Posted : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
Balachundhar Subramaniam, Beth Israel Deaconess Medical Center

Brief Summary:
Investigators will assess the incidence and duration of postoperative delirium in patients ≥60 years old undergoing coronary artery bypass grafting (CABG), with/without valve surgery (aortic and/or mitral) based on different regimens for postoperative sedation and analgesia. Patients will receive either intravenous (IV) dexmedetomidine and IV acetaminophen or standard postoperative management using IV propofol with morphine or hydromorphone. The Confusion Assessment Method (CAM) will be used to assess delirium in these patients. Investigators also seek to compare postoperative (48 hours) analgesic requirements in patients with or without IV acetaminophen. Investigators will finally assess postoperative cognition in post-surgical patients up to one year post-discharge using a cognitive assessment scale.

Condition or disease Intervention/treatment Phase
Delirium Drug: IV acetaminophen & IV propofol Drug: IV acetaminophen & IV dexmedetomidine Drug: IV propofol & placebo Drug: IV dexmedetomidine & placebo Phase 4

Detailed Description:

This is a prospective, randomized, placebo-controlled, triple-blinded, factorial design study consisting of 120 patients who were randomized and received a study intervention. Intravenous dexmedetomidine and acetaminophen will be compared to the standard sedation/analgesic propofol and opioid regimen.

After obtaining informed consent, study subjects will be randomized by an unblinded investigator and receive a specific combination of both sedatives and analgesic medications. Sedatives will include either IV propofol or IV dexmedetomidine, and analgesics IV acetaminophen or placebo (100 mL 0.9% NaCl equivalent to the administered volume of IV acetaminophen). Subjects will be allocated in a 1:1:1:1 fashion into the following four treatment arms: 1. IV acetaminophen with IV propofol, 2. IV acetaminophen with IV dexmedetomidine, 3. IV propofol with placebo, or 4. IV dexmedetomidine with placebo. Sedation and analgesia protocols will begin while patients are in the OR and continue as they are transferred to the Cardiovascular Intensive Care Unit (CVICU). The medications for sedation will be weight based (loading infusion of 0.5 - 1 µg/kg given over 10 minutes followed by a maintenance infusion of 0.1-1.4 µg/kg/hr for IV dexmedetomidine, or 20-100 µg/kg/min for IV propofol). Postoperative sedation is administrated 4-6 hours before patients are woken up in the CVICU. IV Acetaminophen (1g or 100mL) will be given every 6 hours for 48 hours to patients randomized to this drug. The volume of the placebo will be administered in respective groups in the same timeframe. Oral acetaminophen will be continued until discharge in all patients. All groups will also receive bolus doses of opioids (IV morphine or hydromorphone) as needed for breakthrough pain.

Patients will be administered a preoperative (baseline) and a series of post-operative evaluations to assess delirium by a blinded investigator. Baseline assessments will include the Montreal Cognitive Assessment (MoCA), days of the week (DOW), months of the year (MOY), Delirium Symptom Interview (DSI), the Geriatric Depression Scale (GDS) and the Confusion Assessment Method (CAM). Daily cognitive assessments will include the DSI, CAM, and a standard cognitive assessment. At discharge, the MoCA, DOW, MOY, DSI, and CAM will be given. Follow-up assessments will be conducted at 1 month and 1 year post-discharge and will include the telephonic MoCA, DSI, GDS and CAM. The delirium research assessments will not be provided to the treating clinicians. Treating clinicians will assess and treat delirium as usual, including assessment and correction of reversible causes, behavioral management, and use of IV haloperidol as needed for agitation. Rescue doses of haloperidol will be recorded in the study.

Blood will be collected from all subjects at the time of the baseline assessment, post-operation day 1 (POD1) while in ICU, POD 2 in the ICU, and within 48 hours of discharge. Two sets of 10 mL will be collected at each time point, with a total of 80mL of blood per patient. Efforts will be made to efficiently draw blood through the patient's arterial line at baseline or add onto to scheduled draws with phlebotomy. The plasma and buffy coat will be separated from the blood, aliquoted into labeled vials, and stored in a biomarker bank at -80°C for future use.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery in Adult Patients 60 Years of Age and Older
Actual Study Start Date : October 2015
Actual Primary Completion Date : May 2018
Actual Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IV acetaminophen & IV propofol

20-100 µg/kg/min IV propofol given for 4-6 hours before the patients are woken up in the ICU

1g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

Drug: IV acetaminophen & IV propofol
use of IV tylenol and IV propofol for pain and sedation (respectively)
Other Names:
  • Ofirmev
  • Diprivan

Experimental: IV acetaminophen & IV dexmedetomidine

A loading infusion of 0.5 - 1 µg/kg given over 10 minutes will be administered. After the loading infusion, a maintenance infusion of 0.1-1.4 µg/kg/hr will be initiated.

1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

Drug: IV acetaminophen & IV dexmedetomidine
use of IV tylenol and IV dexmedetomidine for pain and sedation (respectively)
Other Names:
  • Ofirmev
  • Precedex

Active Comparator: IV propofol & placebo
20-100 µg/kg/min IV propofol given for 4-6 hours before the patients are woken up in the ICU Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl.
Drug: IV propofol & placebo
use of IV propofol for sedation and morphine, the drug of choice for cardiac pain
Other Name: Diprivan

Active Comparator: IV dexmedetomidine & placebo
0.1-1.0 µg/kg/hour IV dexmedetomidine given for 4-6 hours before the patients are woken up in the ICU Volume of the placebo (saline) will match that of i.v. acetaminophen at 100ml 0.9% NaCl.
Drug: IV dexmedetomidine & placebo
use of IV dexmedetomidine for sedation and morphine, the drug of choice for cardiac pain
Other Name: Precedex




Primary Outcome Measures :
  1. Incidence of Delirium [ Time Frame: Participants will be followed for the duration of the hospital stay, an average of 5 days ]
    Incidence of delirium will be analyzed between patients treated with and without IV acetaminophen, measured from 24 hours post-operation and daily until discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM).


Secondary Outcome Measures :
  1. Duration of Delirium [ Time Frame: Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 month and 1- year following the date of surgery ]
    Duration of delirium will be analyzed, measured from 24 hours post-operation and daily until discharge. Additional measurements will be made at 1 month and 1 year after discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM).

  2. Severity of Delirium [ Time Frame: Participants will be followed for the duration of the hospital stay, an average of 6 days ]
    Severity of delirium will be analyzed, measured from 24 hours post-operation and daily until discharge. The worst severity experienced while in the hospital will be analyzed. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method Severity Score (CAM-S, Confusion Assessment Method-Severity). range 0 [best/no delirium] to 19 [worst]; Minimal Clinical Important Difference (MCID) 2 points

  3. Postoperative Opioid Consumption in Morphine Equivalents [ Time Frame: Participants will be followed for the first 48 hours postoperatively. ]
    Defined by the amount of additional opioid (IV morphine or hydromorphone) and oral acetaminophen medications required in the first 48 hours postoperatively. Values will be converted to morphine equivalents for analysis. Total morphine equivalent is calculated as the sum of (fentanyl dose x 100)+(hydromorphone dose x 4)+morphine dose+(oxycodone dose x 1.5)

  4. Montreal Cognitive Assessment (MoCA) [ Time Frame: On the day of discharge, an average of 6 days ]
    MoCA scores at discharge will be reported in order to assess the occurrence of postoperative cognitive decline. Blinded study staff trained in administering the assessments will collect the data. MoCA is scored on a scale from 0 [worst] to 30 [best]; ǂA MoCA score of 24 would be equivalent to an Mini-Mental State Examination (MMSE) of about 27 or 28. Depending on education and peak intellectual attainment, such a score could be consistent with being either cognitively normal, or having very early mild cognitive impairment. Certainly such a person would be capable of living independently in the community and managing most or all of their affairs.

  5. Hospital Length of Stay [ Time Frame: Measured in days admitted in the hospital, an average of 6 days ]
    Defined by the number of days admitted in the hospital following the completion of surgery.

  6. ICU Length of Stay [ Time Frame: Measured in days admitted in the ICU, an average of 2 days ]
    Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor

  7. Follow up Incidence of Cognitive Dysfunction [ Time Frame: Patients will be assessed for cognitive dysfunction with T-MOCA at 1 month following the date of surgery ]
    The follow up incidence of cognitive dysfunction will be analyzed at 1 month after discharge. T-MoCA is Telephone Montreal Cognitive Assessment Scale (MOCA). The T-MoCA is scored out of 22. The minimum score is 0 (worst) and maximum score is 22 (best). T-MOCA is converted back to 30 (full MOCA) with the help of conversion algorithms to a full MOCA.Example: 19/22 converts back to 30 by performing the following equation: (19×30) ÷ 22. The total converted score is 25.9 or 26/30 which is considered in the normal range.



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:

  • Patients ≥ 60 years of age
  • Undergoing CABG with/without valve (aortic and/or mitral) procedure requiring bypass

Exclusion Criteria:

  • Pre-operative Left Ventricular Ejection Fraction (LVEF) < 30%
  • Emergent or urgent procedures, aortic surgery
  • Pre-existing cognitive impairment (defined based on a short screening assessment), Parkinson's disease, Alzheimer's disease, recent seizures (<3 months)
  • Prophylactic medications for cognitive decline
  • Serum creatinine > 2 mg/dl
  • Liver dysfunction (liver enzymes > 4x the baseline, since patients will have a baseline liver function tests), history and exam suggestive of jaundice
  • Known history of alcohol or drug abuse (>10 drinks per week)
  • Hypersensitivity to any of the study drug and percutaneous procedures
  • Non-English speaking

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): NCT02546765


Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Principal Investigator: Balachundhar Subramaniam, MD, MPH Beth Israel Deaconess Medical Center
  Study Documents (Full-Text)

Documents provided by Balachundhar Subramaniam, Beth Israel Deaconess Medical Center:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Balachundhar Subramaniam, Anesthesiologist, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02546765    
Other Study ID Numbers: 2014P000413
First Posted: September 11, 2015    Key Record Dates
Results First Posted: January 7, 2020
Last Update Posted: April 9, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Balachundhar Subramaniam, Beth Israel Deaconess Medical Center:
analgesics
cardiac surgery
sedation
Additional relevant MeSH terms:
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Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Acetaminophen
Dexmedetomidine
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
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
Antipyretics