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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)

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: 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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Treatment
Condition Delirium
Interventions Drug: IV acetaminophen & IV propofol
Drug: IV acetaminophen & IV dexmedetomidine
Drug: IV propofol & placebo
Drug: IV dexmedetomidine & placebo
Enrollment 140
Recruitment Details  
Pre-assignment Details After signing the informed consent, 19 withdrew prior to randomization. (8 patient withdrawals, 8 found ineligible, 1 withdrawn because of inappropriate behavior and emotional lability, 1 withdrawn after entering and receiving intervention in another trial, 1 withdrawn because of inability to complete baseline assessment for same-day admission)
Arm/Group Title IV Acetaminophen & IV Propofol IV Acetaminophen & IV Dexmedetomidine IV Propofol & Placebo IV Dexmedetomidine & Placebo
Hide Arm/Group Description

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

IV acetaminophen & IV propofol: use of IV tylenol and IV propofol for pain and sedation (respectively)

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

IV acetaminophen & IV dexmedetomidine: use of IV tylenol and IV dexmedetomidine for pain and sedation (respectively)

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.

IV propofol & placebo: use of IV propofol for sedation and morphine, the drug of choice for cardiac pain

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.

IV dexmedetomidine & placebo: use of IV dexmedetomidine for sedation and morphine, the drug of choice for cardiac pain

Period Title: Overall Study
Started 31 30 30 30
Completed 31 29 [1] 30 30
Not Completed 0 1 0 0
Reason Not Completed
Withdrawal by Subject             0             1             0             0
[1]
29 Received study drug; 1 withdrew before surgery and after randomization
Arm/Group Title Acetaminophen-Propofol Acetaminophen-Dexmedetomidine Placebo-Propofol Placebo-Dexmedetomidine Total
Hide Arm/Group Description Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous Propofol as sedative until extubation Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous dexmedetomidine as sedative until extubation Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Propofol as a sedative until extubation Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Dexmedetomidine as a sedative until extubation Total of all reporting groups
Overall Number of Baseline Participants 31 29 30 30 120
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
70
(66 to 75)
64
(63 to 72)
71
(64 to 79)
69
(63 to 74)
69
(63 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
Female
7
  22.6%
3
  10.3%
4
  13.3%
5
  16.7%
19
  15.8%
Male
24
  77.4%
26
  89.7%
26
  86.7%
25
  83.3%
101
  84.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
Hispanic or Latino
0
   0.0%
1
   3.4%
2
   6.7%
1
   3.3%
4
   3.3%
Not Hispanic or Latino
31
 100.0%
28
  96.6%
28
  93.3%
29
  96.7%
116
  96.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   3.2%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   3.2%
2
   6.9%
1
   3.3%
1
   3.3%
5
   4.2%
White
29
  93.5%
26
  89.7%
28
  93.3%
28
  93.3%
111
  92.5%
More than one race
0
   0.0%
0
   0.0%
1
   3.3%
0
   0.0%
1
   0.8%
Unknown or Not Reported
0
   0.0%
1
   3.4%
0
   0.0%
1
   3.3%
2
   1.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
31 29 30 30 120
Weight  
Median (Inter-Quartile Range)
Unit of measure:  Kg
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
84.1
(79 to 93.2)
89.1
(80.4 to 102)
90
(75.8 to 107)
87.6
(82 to 102)
87
(79.15 to 100.15)
Height  
Median (Inter-Quartile Range)
Unit of measure:  Cms
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
170.2
(167.6 to 173.3)
173
(167.6 to 180.3)
175.1
(167.6 to 180)
172.7
(167.6 to 178)
172.7
(167.6 to 179)
Body mass index  
Median (Inter-Quartile Range)
Unit of measure:  Kg/m^2
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
28.5
(26.6 to 32.3)
29.7
(26.6 to 32.3)
29.2
(25.9 to 34.3)
29.4
(27 to 32)
29.44
(26.53 to 32.69)
Surgical Characteristics-  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
CABG surgery 19 19 23 18 79
CABG+mitral 1 1 0 0 2
CABG+aortic 10 8 6 8 32
Other 1 1 1 4 7
Number of arteries affected  
Median (Inter-Quartile Range)
Unit of measure:  Arteries
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
3
(2 to 3)
3
(2 to 4)
3
(2 to 3)
3
(2 to 3)
3
(2 to 3)
Preoperative statin use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
29
  93.5%
24
  82.8%
27
  90.0%
25
  83.3%
105
  87.5%
Cross-clamp time  
Median (Inter-Quartile Range)
Unit of measure:  Minutes
Number Analyzed 31 participants 29 participants 30 participants 30 participants 120 participants
78
(66 to 87)
67
(58 to 84)
64
(54 to 96)
73
(60 to 93)
75
(59 to 93)
1.Primary Outcome
Title Incidence of Delirium
Hide Description 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).
Time Frame Participants will be followed for the duration of the hospital stay, an average of 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study.
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
Those who received IV acetaminophen for analgesia and Propofol for sedation
Those who received Placebo for analgesia and dexmedetomidine for sedation
Patients who received placebo for analgesia and Propofol for sedation
Overall Number of Participants Analyzed 29 31 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
2
   6.9%
4
  12.9%
8
  26.7%
9
  30.0%
2.Secondary Outcome
Title Duration of Delirium
Hide Description 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).
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
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study. Therefore, participants were analyzed for primary analgesic use (N=60 in each group)
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Those who received Acetaminophen for analgesia and dexmedetomidine for sedation
Those who received acetaminophen for analgesia and propofol for sedation
Those who received placebo for analgesia and dexmedetomidine for sedation
Those who received Placebo for sedation and Propofol for analgesia
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: days
1
(1 to 1)
1
(1 to 1)
1
(1 to 3)
3
(2 to 3)
3.Secondary Outcome
Title Severity of Delirium
Hide Description 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
Time Frame Participants will be followed for the duration of the hospital stay, an average of 6 days
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study. Therefore, participants were analyzed for primary analgesic use (N=60 in each group)
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Those who received acetaminophen for analgesia and dexmedetomidine for sedation
Those who received acetaminophen for analgesia and propofol for sedation
Those who received placebo for analgesia and dexmedetomidine for sedation
Those who received placebo for analgesia and propofol for sedation
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
10
(9 to 11)
8
(6 to 10)
6
(6 to 9)
9
(8 to 11)
4.Secondary Outcome
Title Postoperative Opioid Consumption in Morphine Equivalents
Hide Description 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)
Time Frame Participants will be followed for the first 48 hours postoperatively.
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study.
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
Those who received acetaminophen for analgesia and propofol for sedation
Those who received Placebo for analgesia and dexmedetomidine for sedation
Those who received placebo for analgesia and dexmedetomidine for sedation
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: mcg
10050
(5094 to 12530)
12611
(10026 to 17639)
11382
(10032 to 18840)
12616
(10116 to 22590)
5.Secondary Outcome
Title Montreal Cognitive Assessment (MoCA)
Hide Description 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.
Time Frame On the day of discharge, an average of 6 days
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study.
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
Those who received placebo for analgesia and propofol for sedation
Those who received placebo for analgesia and dexmedetomidine for sedation
Those who received Placebo for analgesia and Propofol for sedation
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: score on a scale
23
(22 to 26)
24
(22 to 26)
24
(20 to 26)
23
(21 to 26)
6.Secondary Outcome
Title Hospital Length of Stay
Hide Description Defined by the number of days admitted in the hospital following the completion of surgery.
Time Frame Measured in days admitted in the hospital, an average of 6 days
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study.
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
Those who received acetaminophen for analgesia and propofol for sedation
Those who received Placebo for analgesia and dexmedetomidine for sedation
Those who received placebo for analgesia and propofol for sedation
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: days
8
(6 to 9)
8
(6 to 11)
9
(7 to 11)
8
(6 to 11)
7.Secondary Outcome
Title ICU Length of Stay
Hide Description Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor
Time Frame Measured in days admitted in the ICU, an average of 2 days
Hide Outcome Measure Data
Hide Analysis Population Description
This is a 2 x 2 cross over study.
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Patients who received intravenous Acetaminophen for analgesia and Dexmedetomidine for sedation
Those who received acetaminophen for analgesia and propofol for sedation
Those who received Placebo for analgesia and Dexmedetomidine for sedation
Those who received Placebo for analgesia and Propofol for sedation
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: hours
28.8
(24.9 to 43.5)
30.3
(25.3 to 52.8)
49.1
(29 to 92.9)
29.3
(25.7 to 74.3)
8.Secondary Outcome
Title Follow up Incidence of Cognitive Dysfunction
Hide Description 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.
Time Frame Patients will be assessed for cognitive dysfunction with T-MOCA at 1 month following the date of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Telephone (T)-MOCA at 1 month. This is a 2 x 2 cross over study.
Arm/Group Title Acetaminophen and Dexmedetomidine Acetaminophen and Propofol Placebo and Dexmedetomidine Placebo and Propofol
Hide Arm/Group Description:
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
Those who received acetaminophen for analgesia and propofol for sedation
Those who received placebo for analgesia and dexmedetomidine for sedation
Those who received Placebo for analgesia and Propofol for sedation
Overall Number of Participants Analyzed 29 31 30 30
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
17
(16 to 20)
18
(16 to 20)
19
(17.5 to 21)
18
(16 to 19.5)
Time Frame During hospital stay, an average of 7 days
Adverse Event Reporting Description These were outcomes that are collected by the Society of Thoracic Surgery
 
Arm/Group Title Acetaminophen-Propofol Acetaminophen-Dexmedetomidine Placebo-Propofol Placebo-Dexmedetomidine
Hide Arm/Group Description Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous Propofol as sedative until extubation Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous dexmedetomidine as sedative until extubation Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Propofol as a sedative until extubation Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Dexmedetomidine as a sedative until extubation
All-Cause Mortality
Acetaminophen-Propofol Acetaminophen-Dexmedetomidine Placebo-Propofol Placebo-Dexmedetomidine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/31 (0.00%)      0/29 (0.00%)      0/30 (0.00%)      0/30 (0.00%)    
Hide Serious Adverse Events
Acetaminophen-Propofol Acetaminophen-Dexmedetomidine Placebo-Propofol Placebo-Dexmedetomidine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/31 (0.00%)      0/29 (0.00%)      0/30 (0.00%)      0/30 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Acetaminophen-Propofol Acetaminophen-Dexmedetomidine Placebo-Propofol Placebo-Dexmedetomidine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/31 (45.16%)      7/29 (24.14%)      7/30 (23.33%)      14/30 (46.67%)    
Cardiac disorders         
Hypotension  1 [1]  14/31 (45.16%)  14 7/29 (24.14%)  7 7/30 (23.33%)  7 14/30 (46.67%)  14
Bradycardia  2 [2]  1/31 (3.23%)  1 0/29 (0.00%)  0 0/30 (0.00%)  0 1/30 (3.33%)  1
1
Term from vocabulary, ICU hypotension
2
Term from vocabulary, ICU bradycardia
Indicates events were collected by systematic assessment
[1]
Hypotension during the ICU admission
[2]
ICU bradycardia reported as Heart rate < 60 beats/min
This single center study with restrictive inclusion may place some limitations on generalizability.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Balachundhar Subramaniam
Organization: Beth Israel Deaconess Medical Center
Phone: 6176320706 ext 6176320706
EMail: bsubrama@bidmc.harvard.edu
Publications:
Layout table for additonal information
Responsible Party: Balachundhar Subramaniam, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02546765    
Other Study ID Numbers: 2014P000413
First Submitted: January 13, 2015
First Posted: September 11, 2015
Results First Submitted: November 14, 2019
Results First Posted: January 7, 2020
Last Update Posted: April 9, 2020