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The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial (PODCAST)

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: NCT01690988
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : May 2, 2018
Last Update Posted : June 6, 2018
Sponsor:
Collaborators:
Asan Medical Center
Weill Medical College of Cornell University
Harvard Medical School
Medical College of Wisconsin
Memorial Sloan Kettering Cancer Center
Postgraduate Institute of Medical Education and Research
University of Bern
University of Michigan
University of Manitoba
University Health Network, Toronto
Virginia Mason Hospital/Medical Center
Information provided by (Responsible Party):
Michael Avidan, Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Delirium
Interventions Drug: Ketamine (0.5 mg/kg)
Drug: Normal Saline (placebo)
Drug: Ketamine (1 mg/kg)
Enrollment 746
Recruitment Details  
Pre-assignment Details 746 participants were consented to the study; however only 672 were randomly assigned as 74 participants were determined ineligible after consent. Reasons for ineligibility: operations were cancelled or patients withdrew from the study, etc.
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Period Title: Overall Study
Started 227 222 223
Completed 221 217 216
Not Completed 6 5 7
Reason Not Completed
Withdrawal by Subject             2             2             3
Physician Decision             0             0             1
Operation Cancelled             1             1             0
Determined ineligible             1             0             0
Death             1             1             1
Sedated             1             1             2
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg) Total
Hide Arm/Group Description

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Total of all reporting groups
Overall Number of Baseline Participants 227 222 223 672
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 227 participants 222 participants 223 participants 672 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
56
  24.7%
59
  26.6%
61
  27.4%
176
  26.2%
>=65 years
171
  75.3%
163
  73.4%
162
  72.6%
496
  73.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 227 participants 222 participants 223 participants 672 participants
70  (7.2) 70  (6.9) 70  (7.3) 70  (7.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 227 participants 222 participants 223 participants 672 participants
Female
83
  36.6%
87
  39.2%
84
  37.7%
254
  37.8%
Male
144
  63.4%
135
  60.8%
139
  62.3%
418
  62.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 227 participants 222 participants 223 participants 672 participants
United States 147 147 149 443
Canada 63 61 59 183
India 6 5 5 16
South Korea 11 9 10 30
1.Primary Outcome
Title Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3
Hide Description

According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.

To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS <-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.

The primary comparison will be between the combined ketamine groups and the placebo group.

Time Frame Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients
Hide Outcome Measure Data
Hide Analysis Population Description
Of all 672 participants, data were analyzed AM and PM and post operative day 1 through day 3 for screened participants with a CAM. The overall incidence of delirium were compared, Ketamine 0.5 mg/kg and 1 mg/kg groups were combined as per-specified in the study protocol.
Arm/Group Title Ketamine (0.5 mg/kg and 1 mg/kg) Normal Saline (Placebo)
Hide Arm/Group Description:

Both the 0.5 mg/kg and the 1mg/kg doses groups of Ketamine were combined for analysis)

Low dose Ketamine (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

Overall Number of Participants Analyzed 438 217
Measure Type: Count of Participants
Unit of Measure: Participants
85
  19.4%
43
  19.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketamine (0.5 mg/kg and 1 mg/kg), Normal Saline (Placebo)
Comments The primary analysis was a comparison between the placebo control group and the combined ketamine groups
Type of Statistical Test Other
Comments Test of independence
Statistical Test of Hypothesis P-Value 0.912
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
-6.07 to 7.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.301
Estimation Comments Difference in delirium incidence between placebo control and combined ketamine groups.
2.Secondary Outcome
Title Daily Maximum Pain Recorded
Hide Description Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.
Time Frame Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine (0.5 mg/kg ) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description:

Low dose ketamine (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction anesthesia or administration of sedative medications.

Overall Number of Participants Analyzed 227 222 223
Median (Inter-Quartile Range)
Unit of Measure: participants
VAS day 1
70
(40 to 87)
63.5
(43 to 82)
68
(37.5 to 90)
VAS day 2
56
(30 to 80)
59
(31 to 80)
57.5
(27 to 81)
VAS day 3
46
(22.5 to 75)
52.5
(25.5 to 75)
47
(23 to 74)
BPS/BPS-NI day 1
4
(3 to 5)
4
(3 to 4)
4
(3 to 5)
BPS/BPS-NI 2
4
(3 to 4)
3
(3 to 4)
3
(3 to 4)
BPS/BPS-NI 3
3
(3 to 4)
3
(3 to 4)
3
(3 to 4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketamine (0.5 mg/kg ), Normal Saline (Placebo)
Comments We compared the combined average pain level (pain level at rest, taking a deep breath, and/or when moving) over the entire day (AM and PM).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.964
Comments [Not Specified]
Method ANOVA
Comments one-way
3.Secondary Outcome
Title Median Opioid Consumption
Hide Description

Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively

Opioid Drugs included:

* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)

Time Frame Postoperative days 0-3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description:

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Overall Number of Participants Analyzed 227 222 223
Median (Full Range)
Unit of Measure: mg
88.9
(46.5 to 175.5)
94.7
(48 to 199)
78.7
(43.8 to 169)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketamine (0.5 mg/kg), Normal Saline (Placebo), Ketamine (1 mg/kg)
Comments

All morphine equivalent drugs consumed by patients perioperatively

Opioid Drugs included:

* Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.476
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
4.Secondary Outcome
Title Number of Patients With Postoperative Nausea and Vomiting
Hide Description

Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they "currently have nausea/vomiting" AM & PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3

The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.

Time Frame Postoperative days 1-3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description:

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Overall Number of Participants Analyzed 227 222 223
Measure Type: Count of Participants
Unit of Measure: Participants
72
  31.7%
73
  32.9%
64
  28.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketamine (0.5 mg/kg), Normal Saline (Placebo)
Comments Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they "currently have nausea/vomiting" AM & PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.572
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter frequency-test
Estimated Value 0.572
Estimation Comments [Not Specified]
5.Secondary Outcome
Title ICU and/or Hospital Length of Stay
Hide Description Assessed from patients' medical charts
Time Frame Postoperative period
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measure data were not collected.
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description:

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Adverse Outcomes (Number of Patients With Hallucinations)
Hide Description Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit
Time Frame Postoperative days 1-3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description:

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Overall Number of Participants Analyzed 227 222 223
Measure Type: Count of Participants
Unit of Measure: Participants
45
  19.8%
40
  18.0%
62
  27.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketamine (0.5 mg/kg), Normal Saline (Placebo), Ketamine (1 mg/kg)
Comments Frequency of patients reporting hallucinations using the DSAQ instrument.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
7.Secondary Outcome
Title Adverse Outcomes (Number of Patients With Nightmares)
Hide Description Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit
Time Frame Postoperative days 1-3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description:

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Overall Number of Participants Analyzed 227 222 223
Measure Type: Count of Participants
Unit of Measure: Participants
27
  11.9%
18
   8.1%
34
  15.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ketamine (0.5 mg/kg), Normal Saline (Placebo), Ketamine (1 mg/kg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments Patients where asked whether "Following their surgery they had bad dreams or nightmares the response choices: Yes/No question The incidence of hallucination and nightmares were assessed separately and compared across the three study group.
Method Chi-squared
Comments [Not Specified]
Time Frame Assessed up to 3 days (POD 0-3).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Hide Arm/Group Description

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (0.5 mg/kg): Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Intravenous normal saline

Normal Saline (placebo): Normal saline IV following induction of anesthesia or administration of sedative medications

High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Ketamine (1 mg/kg): High dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

All-Cause Mortality
Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/227 (0.00%)      2/220 (0.91%)      0/223 (0.00%)    
Hide Serious Adverse Events
Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/227 (0.00%)      0/222 (0.00%)      0/223 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ketamine (0.5 mg/kg) Normal Saline (Placebo) Ketamine (1 mg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   90/227 (39.65%)      82/222 (36.94%)      86/223 (38.57%)    
Blood and lymphatic system disorders       
Anaemia/Bleeding   19/227 (8.37%)  19 13/222 (5.86%)  13 20/223 (8.97%)  20
Cardiac disorders       
Tachycardia   8/227 (3.52%)  8 8/222 (3.60%)  8 8/223 (3.59%)  8
Gastrointestinal disorders       
Gastrointestinal   9/227 (3.96%)  9 8/222 (3.60%)  8 6/223 (2.69%)  6
Infections and infestations       
Infection   16/227 (7.05%)  16 18/222 (8.11%)  18 15/223 (6.73%)  15
Nervous system disorders       
Atrial Fibriliation   21/227 (9.25%)  21 19/222 (8.56%)  19 15/223 (6.73%)  15
Renal and urinary disorders       
Renal   13/227 (5.73%)  13 11/222 (4.95%)  11 8/223 (3.59%)  8
Vascular disorders       
Hypotension   11/227 (4.85%)  11 11/222 (4.95%)  11 9/223 (4.04%)  9
Hypertension   1/227 (0.44%)  1 3/222 (1.35%)  3 5/223 (2.24%)  5
Indicates events were collected by systematic assessment
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. Michael Avidan
Organization: Washington University School of Medicine
Phone: 314-747-4155
EMail: avidanm@wustl.edu
Layout table for additonal information
Responsible Party: Michael Avidan, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01690988    
Other Study ID Numbers: 201206071
First Submitted: August 7, 2012
First Posted: September 24, 2012
Results First Submitted: September 15, 2017
Results First Posted: May 2, 2018
Last Update Posted: June 6, 2018