Trial Outcomes & Findings for The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction (NCT NCT02554253)

NCT ID: NCT02554253

Last Updated: 2022-02-15

Results Overview

Pre and postoperative cognitive studies will be performed to assess change in cognitive function. Postoperative cognitive dysfunction (POCD) was defined a-priori as a decline of decline of \>1 standard deviation (i.e. z-score decline of \> 1) on at least 2 neurocognitive tests. The neurocognitive tests utilized include Trail making Test A, Trail making Test B, Hopkins Verbal Learning Test-Revised Learning trials, Hopkins Verbal Learning Test-Revised Delayed Recall, Digit Span, Controlled Oral Word Association Test, Stroop color/word test, and the Mini Mental Status Examination.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.

Results posted on

2022-02-15

Participant Flow

Participants who were undergoing complex cardiac surgery at Mayo Clinic were recruited between August 2015 and October 2019.

Of the 265 patients assessed for eligibility, 52 were randomized to study groups. 8 did not meet inclusion criteria, 97 declined to participate, 96 were unable to be contacted before surgery, and 12 were unable to coordinate preoperative testing before surgery.

Participant milestones

Participant milestones
Measure
Ketamine
Ketamine induction Ketamine: Ketamine used for induction
Propofol
Propofol induction Propofol: Propofol for induction
Overall Study
STARTED
26
26
Overall Study
COMPLETED
25
24
Overall Study
NOT COMPLETED
1
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Ketamine
Ketamine induction Ketamine: Ketamine used for induction
Propofol
Propofol induction Propofol: Propofol for induction
Overall Study
ineligible after enrollment
1
0
Overall Study
converted to transcatheter procedure
0
1
Overall Study
received both drugs
0
1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ketamine
n=25 Participants
Ketamine induction Ketamine: Ketamine used for induction
Propofol
n=24 Participants
Propofol induction Propofol: Propofol used for induction
Total
n=49 Participants
Total of all reporting groups
Age, Continuous
76.4 years
STANDARD_DEVIATION 3.5 • n=25 Participants
76.1 years
STANDARD_DEVIATION 5.3 • n=24 Participants
76.3 years
STANDARD_DEVIATION 4.4 • n=49 Participants
Sex: Female, Male
Female
9 Participants
n=25 Participants
10 Participants
n=24 Participants
19 Participants
n=49 Participants
Sex: Female, Male
Male
16 Participants
n=25 Participants
14 Participants
n=24 Participants
30 Participants
n=49 Participants
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.
Region of Enrollment
United States
25 Participants
n=25 Participants
24 Participants
n=24 Participants
49 Participants
n=49 Participants
Trail Making Test A
-0.1 Z score
STANDARD_DEVIATION 0.8 • n=25 Participants
0 Z score
STANDARD_DEVIATION 1.1 • n=24 Participants
0.0 Z score
STANDARD_DEVIATION 1.0 • n=49 Participants
Trail Making Test B
0.2 Z score
STANDARD_DEVIATION 1.0 • n=25 Participants
-0.1 Z score
STANDARD_DEVIATION 1.1 • n=24 Participants
0.1 Z score
STANDARD_DEVIATION 1.1 • n=49 Participants
Hopkins Verbal Learning Test-Revised (HVLT-R) Learning Trials test
-0.7 Z score
STANDARD_DEVIATION 0.9 • n=25 Participants
-0.5 Z score
STANDARD_DEVIATION 0.8 • n=24 Participants
-0.6 Z score
STANDARD_DEVIATION 0.9 • n=49 Participants
Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall
-0.9 Z score
STANDARD_DEVIATION 1.3 • n=25 Participants
-0.8 Z score
STANDARD_DEVIATION 1.2 • n=24 Participants
-0.9 Z score
STANDARD_DEVIATION 1.2 • n=49 Participants
Hopkins Verbal Learning Test-Revised (HVLT-R) Digit Span
0.2 Z score
STANDARD_DEVIATION 0.8 • n=25 Participants
0.1 Z score
STANDARD_DEVIATION 1.0 • n=24 Participants
0.2 Z score
STANDARD_DEVIATION 0.9 • n=49 Participants
Controlled Oral Word Association Test (COWAT)
0.1 Z score
STANDARD_DEVIATION 0.8 • n=25 Participants
0.1 Z score
STANDARD_DEVIATION 0.8 • n=24 Participants
0.1 Z score
STANDARD_DEVIATION 0.8 • n=49 Participants
Stroop color/word test
-0.3 Z score
STANDARD_DEVIATION 1.0 • n=25 Participants
-0.6 Z score
STANDARD_DEVIATION 1.3 • n=24 Participants
-0.4 Z score
STANDARD_DEVIATION 1.1 • n=49 Participants
Mini-Mental Status Exam
0.7 Z score
STANDARD_DEVIATION 0.9 • n=25 Participants
0.4 Z score
STANDARD_DEVIATION 1.1 • n=24 Participants
0.6 Z score
STANDARD_DEVIATION 1.0 • n=49 Participants

PRIMARY outcome

Timeframe: Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.

Population: Intent to treat population

Pre and postoperative cognitive studies will be performed to assess change in cognitive function. Postoperative cognitive dysfunction (POCD) was defined a-priori as a decline of decline of \>1 standard deviation (i.e. z-score decline of \> 1) on at least 2 neurocognitive tests. The neurocognitive tests utilized include Trail making Test A, Trail making Test B, Hopkins Verbal Learning Test-Revised Learning trials, Hopkins Verbal Learning Test-Revised Delayed Recall, Digit Span, Controlled Oral Word Association Test, Stroop color/word test, and the Mini Mental Status Examination.

Outcome measures

Outcome measures
Measure
Ketamine
n=25 Participants
Ketamine induction Ketamine: Ketamine used for induction
Propofol
n=24 Participants
Propofol induction Propofol: Propofol for induction
Number of Patients With Postoperative Cognitive Dysfunction
16 Participants
10 Participants

SECONDARY outcome

Timeframe: Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.

Population: Intent to treat

AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria including an increase in serum creatinine ≥0.3 mg/dL within 48 hours, an increase in serum creatinine to ≥1.5 times baseline within 7 days, and urine output \< 0.5 mL/kg/hr for 6 hours.

Outcome measures

Outcome measures
Measure
Ketamine
n=25 Participants
Ketamine induction Ketamine: Ketamine used for induction
Propofol
n=24 Participants
Propofol induction Propofol: Propofol for induction
Number of Patients With Acute Kidney Injury
6 Participants
12 Participants

SECONDARY outcome

Timeframe: Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.

Delirium was defined as a positive CAM (Confusion assessment method) score. CAM score was recorded every 12 hours postoperatively as per routine. The CAM consists of 4 features: 1-Onset, 2-Inattention, 3-Disorganized thinking, and 4-altered level of consciousness. The diagnosis of delirium by CAM is based on the presence of features 1 and 2, and either 3 or 4. The score is either positive or negative. Positive means the patient has delirium and negative indicates the patient is not delirious.

Outcome measures

Outcome measures
Measure
Ketamine
n=25 Participants
Ketamine induction Ketamine: Ketamine used for induction
Propofol
n=24 Participants
Propofol induction Propofol: Propofol for induction
Number of Patients Who Develop Postoperative Delirium
0 Participants
1 Participants

Adverse Events

Ketamine

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Propofol

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ketamine
n=25 participants at risk
Ketamine induction Ketamine: Ketamine used for induction
Propofol
n=24 participants at risk
Propofol induction Propofol: Propofol used for induction
Cardiac disorders
Complete heart block
0.00%
0/25 • Surgery to discharge, up to 10 days postoperatively
4.2%
1/24 • Number of events 1 • Surgery to discharge, up to 10 days postoperatively
Cardiac disorders
RV failure
4.0%
1/25 • Number of events 1 • Surgery to discharge, up to 10 days postoperatively
0.00%
0/24 • Surgery to discharge, up to 10 days postoperatively
Respiratory, thoracic and mediastinal disorders
Respiratory failure
4.0%
1/25 • Number of events 1 • Surgery to discharge, up to 10 days postoperatively
0.00%
0/24 • Surgery to discharge, up to 10 days postoperatively
Gastrointestinal disorders
Intestinal perforation
4.0%
1/25 • Number of events 1 • Surgery to discharge, up to 10 days postoperatively
0.00%
0/24 • Surgery to discharge, up to 10 days postoperatively
Renal and urinary disorders
Acute kidney injury
4.0%
1/25 • Number of events 1 • Surgery to discharge, up to 10 days postoperatively
0.00%
0/24 • Surgery to discharge, up to 10 days postoperatively

Other adverse events

Adverse event data not reported

Additional Information

Erica Wittwer

Mayo Clinic

Phone: 5072559814

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place