- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02546765
Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery (DEXACET)
Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery in Adult Patients 60 Years of Age and Older
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: TRIPLE
Arms and Interventions
Participant Group / 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 |
use of IV tylenol and IV propofol for pain and sedation (respectively)
Other Names:
|
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 |
use of IV tylenol and IV dexmedetomidine for pain and sedation (respectively)
Other Names:
|
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.
|
use of IV propofol for sedation and morphine, the drug of choice for cardiac pain
Other Names:
|
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.
|
use of IV dexmedetomidine for sedation and morphine, the drug of choice for cardiac pain
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Participants will be followed for the duration of the hospital stay, an average of 5 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
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
|
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
|
Participants will be followed for the duration of the hospital stay, an average of 6 days
|
Postoperative Opioid Consumption in Morphine Equivalents
Time Frame: Participants will be followed for the first 48 hours postoperatively.
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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)
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Participants will be followed for the first 48 hours postoperatively.
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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.
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On the day of discharge, an average of 6 days
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Hospital Length of Stay
Time Frame: Measured in days admitted in the hospital, an average of 6 days
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Defined by the number of days admitted in the hospital following the completion of surgery.
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Measured in days admitted in the hospital, an average of 6 days
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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
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Measured in days admitted in the ICU, an average of 2 days
|
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.
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Patients will be assessed for cognitive dysfunction with T-MOCA at 1 month following the date of surgery
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Collaborators and Investigators
Publications and helpful links
General Publications
- Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.
- Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available. Erratum In: N Engl J Med. 2006 Apr 13;354(15):1655.
- Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, Khuri SF, Lipsitz LA, Ramlawi B, Levitsky S, Marcantonio ER. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009 Jan 20;119(2):229-36. doi: 10.1161/CIRCULATIONAHA.108.795260. Epub 2008 Dec 31.
- Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009 May-Jun;50(3):206-17. doi: 10.1176/appi.psy.50.3.206.
- Lin YY, He B, Chen J, Wang ZN. Can dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? a meta-analysis. Crit Care. 2012 Sep 27;16(5):R169. doi: 10.1186/cc11646.
- Corbett SM, Rebuck JA, Greene CM, Callas PW, Neale BW, Healey MA, Leavitt BJ. Dexmedetomidine does not improve patient satisfaction when compared with propofol during mechanical ventilation. Crit Care Med. 2005 May;33(5):940-5. doi: 10.1097/01.ccm.0000162565.18193.e5.
- Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009 Nov;111(5):1075-84. doi: 10.1097/ALN.0b013e3181b6a783.
- Dasta JF, Jacobi J, Sesti AM, McLaughlin TP. Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: an outcomes analysis. Pharmacotherapy. 2006 Jun;26(6):798-805. doi: 10.1592/phco.26.6.798.
- Holmer Pettersson P, Jakobsson J, Owall A. Plasma concentrations following repeated rectal or intravenous administration of paracetamol after heart surgery. Acta Anaesthesiol Scand. 2006 Jul;50(6):673-7. doi: 10.1111/j.1399-6576.2006.01043.x.
- Subramaniam B, Shankar P, Shaefi S, Mueller A, O'Gara B, Banner-Goodspeed V, Gallagher J, Gasangwa D, Patxot M, Packiasabapathy S, Mathur P, Eikermann M, Talmor D, Marcantonio ER. Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):686-696. doi: 10.1001/jama.2019.0234. Erratum In: JAMA. 2019 Jul 16;322(3):276.
- Shankar P, Mueller A, Packiasabapathy S, Gasangwa D, Patxot M, O'Gara B, Shaefi S, Marcantonio ER, Subramaniam B. Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial. Trials. 2018 Jun 22;19(1):326. doi: 10.1186/s13063-018-2718-0.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Neurologic Manifestations
- Confusion
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Delirium
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Analgesics, Non-Narcotic
- Antipyretics
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Hypnotics and Sedatives
- Propofol
- Dexmedetomidine
- Acetaminophen
Other Study ID Numbers
- 2014P000413
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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