Trial Outcomes & Findings for Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery (NCT NCT02546765)
NCT ID: NCT02546765
Last Updated: 2020-04-09
Results Overview
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).
COMPLETED
PHASE4
140 participants
Participants will be followed for the duration of the hospital stay, an average of 5 days
2020-04-09
Participant Flow
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 (8 patient withdrawals, 8 found ineligible, 1 withdrawn because of inappropriate behavior and emotional lability, 1 withdrawn after entering and receiving intervention in another trial, 1 withdrawn because of inability to complete baseline assessment for same-day admission)
Participant milestones
| Measure |
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
IV acetaminophen \& IV propofol: use of IV tylenol and IV propofol for pain and sedation (respectively)
|
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
IV acetaminophen \& IV dexmedetomidine: use of IV tylenol and IV dexmedetomidine for pain and sedation (respectively)
|
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.
IV propofol \& placebo: use of IV propofol for sedation and morphine, the drug of choice for cardiac pain
|
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.
IV dexmedetomidine \& placebo: use of IV dexmedetomidine for sedation and morphine, the drug of choice for cardiac pain
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
31
|
30
|
30
|
30
|
|
Overall Study
COMPLETED
|
31
|
29
|
30
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
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
IV acetaminophen \& IV propofol: use of IV tylenol and IV propofol for pain and sedation (respectively)
|
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
IV acetaminophen \& IV dexmedetomidine: use of IV tylenol and IV dexmedetomidine for pain and sedation (respectively)
|
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.
IV propofol \& placebo: use of IV propofol for sedation and morphine, the drug of choice for cardiac pain
|
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.
IV dexmedetomidine \& placebo: use of IV dexmedetomidine for sedation and morphine, the drug of choice for cardiac pain
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery
Baseline characteristics by cohort
| Measure |
Acetaminophen-Propofol
n=31 Participants
Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous Propofol as sedative until extubation
|
Acetaminophen-Dexmedetomidine
n=29 Participants
Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous dexmedetomidine as sedative until extubation
|
Placebo-Propofol
n=30 Participants
Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Propofol as a sedative until extubation
|
Placebo-Dexmedetomidine
n=30 Participants
Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Dexmedetomidine as a sedative until extubation
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
70 years
n=93 Participants
|
64 years
n=4 Participants
|
71 years
n=27 Participants
|
69 years
n=483 Participants
|
69 years
n=36 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
19 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
25 Participants
n=483 Participants
|
101 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
31 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
29 Participants
n=483 Participants
|
116 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
5 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
28 Participants
n=483 Participants
|
111 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=93 Participants
|
29 participants
n=4 Participants
|
30 participants
n=27 Participants
|
30 participants
n=483 Participants
|
120 participants
n=36 Participants
|
|
Weight
|
84.1 kg
n=93 Participants
|
89.1 kg
n=4 Participants
|
90 kg
n=27 Participants
|
87.6 kg
n=483 Participants
|
87 kg
n=36 Participants
|
|
Height
|
170.2 cms
n=93 Participants
|
173 cms
n=4 Participants
|
175.1 cms
n=27 Participants
|
172.7 cms
n=483 Participants
|
172.7 cms
n=36 Participants
|
|
Body mass index
|
28.5 kg/m^2
n=93 Participants
|
29.7 kg/m^2
n=4 Participants
|
29.2 kg/m^2
n=27 Participants
|
29.4 kg/m^2
n=483 Participants
|
29.44 kg/m^2
n=36 Participants
|
|
Surgical Characteristics-
CABG surgery
|
19 participants
n=93 Participants
|
19 participants
n=4 Participants
|
23 participants
n=27 Participants
|
18 participants
n=483 Participants
|
79 participants
n=36 Participants
|
|
Surgical Characteristics-
CABG+mitral
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
0 participants
n=27 Participants
|
0 participants
n=483 Participants
|
2 participants
n=36 Participants
|
|
Surgical Characteristics-
CABG+aortic
|
10 participants
n=93 Participants
|
8 participants
n=4 Participants
|
6 participants
n=27 Participants
|
8 participants
n=483 Participants
|
32 participants
n=36 Participants
|
|
Surgical Characteristics-
Other
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
4 participants
n=483 Participants
|
7 participants
n=36 Participants
|
|
Number of arteries affected
|
3 arteries
n=93 Participants
|
3 arteries
n=4 Participants
|
3 arteries
n=27 Participants
|
3 arteries
n=483 Participants
|
3 arteries
n=36 Participants
|
|
Preoperative statin use
|
29 Participants
n=93 Participants
|
24 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
25 Participants
n=483 Participants
|
105 Participants
n=36 Participants
|
|
Cross-clamp time
|
78 minutes
n=93 Participants
|
67 minutes
n=4 Participants
|
64 minutes
n=27 Participants
|
73 minutes
n=483 Participants
|
75 minutes
n=36 Participants
|
PRIMARY outcome
Timeframe: Participants will be followed for the duration of the hospital stay, an average of 5 daysPopulation: This is a 2 x 2 cross over study.
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).
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Incidence of Delirium
|
2 Participants
|
4 Participants
|
8 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 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 surgeryPopulation: This is a 2 x 2 cross over study. Therefore, participants were analyzed for primary analgesic use (N=60 in each group)
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).
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Duration of Delirium
|
1 days
Interval 1.0 to 1.0
|
1 days
Interval 1.0 to 1.0
|
1 days
Interval 1.0 to 3.0
|
3 days
Interval 2.0 to 3.0
|
SECONDARY outcome
Timeframe: Participants will be followed for the duration of the hospital stay, an average of 6 daysPopulation: This is a 2 x 2 cross over study. Therefore, participants were analyzed for primary analgesic use (N=60 in each group)
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
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Severity of Delirium
|
10 units on a scale
Interval 9.0 to 11.0
|
8 units on a scale
Interval 6.0 to 10.0
|
6 units on a scale
Interval 6.0 to 9.0
|
9 units on a scale
Interval 8.0 to 11.0
|
SECONDARY outcome
Timeframe: Participants will be followed for the first 48 hours postoperatively.Population: This is a 2 x 2 cross over study.
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)
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Postoperative Opioid Consumption in Morphine Equivalents
|
10050 mcg
Interval 5094.0 to 12530.0
|
12611 mcg
Interval 10026.0 to 17639.0
|
11382 mcg
Interval 10032.0 to 18840.0
|
12616 mcg
Interval 10116.0 to 22590.0
|
SECONDARY outcome
Timeframe: On the day of discharge, an average of 6 daysPopulation: This is a 2 x 2 cross over study.
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.
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Montreal Cognitive Assessment (MoCA)
|
23 score on a scale
Interval 22.0 to 26.0
|
24 score on a scale
Interval 22.0 to 26.0
|
24 score on a scale
Interval 20.0 to 26.0
|
23 score on a scale
Interval 21.0 to 26.0
|
SECONDARY outcome
Timeframe: Measured in days admitted in the hospital, an average of 6 daysPopulation: This is a 2 x 2 cross over study.
Defined by the number of days admitted in the hospital following the completion of surgery.
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Hospital Length of Stay
|
8 days
Interval 6.0 to 9.0
|
8 days
Interval 6.0 to 11.0
|
9 days
Interval 7.0 to 11.0
|
8 days
Interval 6.0 to 11.0
|
SECONDARY outcome
Timeframe: Measured in days admitted in the ICU, an average of 2 daysPopulation: This is a 2 x 2 cross over study.
Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
ICU Length of Stay
|
28.8 hours
Interval 24.9 to 43.5
|
30.3 hours
Interval 25.3 to 52.8
|
49.1 hours
Interval 29.0 to 92.9
|
29.3 hours
Interval 25.7 to 74.3
|
SECONDARY outcome
Timeframe: Patients will be assessed for cognitive dysfunction with T-MOCA at 1 month following the date of surgeryPopulation: Telephone (T)-MOCA at 1 month. This is a 2 x 2 cross over study.
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.
Outcome measures
| Measure |
Acetaminophen and Dexmedetomidine
n=29 Participants
Patients who received intravenous Acetaminophen for analgesia and dexmedetomidine for sedation
|
Acetaminophen and Propofol
n=31 Participants
Those who received IV acetaminophen for analgesia and Propofol for sedation
|
Placebo and Dexmedetomidine
n=30 Participants
Those who received Placebo for analgesia and dexmedetomidine for sedation
|
Placebo and Propofol
n=30 Participants
Patients who received placebo for analgesia and Propofol for sedation
|
|---|---|---|---|---|
|
Follow up Incidence of Cognitive Dysfunction
|
17 units on a scale
Interval 16.0 to 20.0
|
18 units on a scale
Interval 16.0 to 20.0
|
19 units on a scale
Interval 17.5 to 21.0
|
18 units on a scale
Interval 16.0 to 19.5
|
Adverse Events
Acetaminophen-Propofol
Acetaminophen-Dexmedetomidine
Placebo-Propofol
Placebo-Dexmedetomidine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Acetaminophen-Propofol
n=31 participants at risk
Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous Propofol as sedative until extubation
|
Acetaminophen-Dexmedetomidine
n=29 participants at risk
Received Intravenous Acetaminophen 6 hourly for 8 doses and intravenous dexmedetomidine as sedative until extubation
|
Placebo-Propofol
n=30 participants at risk
Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Propofol as a sedative until extubation
|
Placebo-Dexmedetomidine
n=30 participants at risk
Received Intravenous Placebo 6 hourly for 8 doses and Intravenous Dexmedetomidine as a sedative until extubation
|
|---|---|---|---|---|
|
Cardiac disorders
Hypotension
|
45.2%
14/31 • Number of events 14 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
24.1%
7/29 • Number of events 7 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
23.3%
7/30 • Number of events 7 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
46.7%
14/30 • Number of events 14 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
|
Cardiac disorders
Bradycardia
|
3.2%
1/31 • Number of events 1 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
0.00%
0/29 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
0.00%
0/30 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
3.3%
1/30 • Number of events 1 • During hospital stay, an average of 7 days
These were outcomes that are collected by the Society of Thoracic Surgery
|
Additional Information
Dr. Balachundhar Subramaniam
Beth Israel Deaconess Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place