A Phase 4 interventional study of Ketamine and Placebo in Otolaryngeal Cancer, sponsored by Emory University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-08.
Sponsored by Emory University · Phase 4, Interventional, and Other
The goal of this prospective randomized double blinded placebo controlled study is to investigate if a single dose of ketamine in addition to standard anesthesia will reduce the risk of delirium in otolaryngeal cancer patients postoperatively. Ketamine's effect on post-operative pain and opioid use will be measured as well. Electroencephalogram (EEG) will be utilized during the surgical procedure to evaluate its potential as a possible predictive device for delirium.
This is a single center prospective randomized double blinded placebo controlled study.
The primary aim of the study is to optimize the intraoperative treatment protocol for head and neck cancer patients to reduce the incidence of delirium and associated postoperative cognitive dysfunction. Secondary aims are to determine the dose response relationship for intraoperative ketamine and delirium reduction, determine if a single dose of ketamine will reduce post-operative pain and opioid requirements, determine if raw electroencephalogram (EEG) data can predict postoperative delirium during general anesthesia, and to evaluate length of intensive care unit (ICU) and length of hospital stay.
Participants will be randomized to one of three groups after administration of general anesthesia; one dose of .5 mg/kg intravenous (IV) Ketamine, 1.0 mg/kg of IV Ketamine, or IV placebo.
An EEG will be used during the surgical procedure to gather raw data for off line analysis among patients developing post-operative delirium.
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This study's enrollment of 71 is below the median of 120 across 599 interventional studies indexed under Delirium.
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Exclusion Criteria:
Participants undergoing surgery for otolaryngeal cancer will be randomized to receive one dose of IV ketamine at 0.5 mg/kg.
Drug: Ketamine · Device: Electroencephalogram (EEG)
Participants undergoing surgery for otolaryngeal cancer will be randomized to receive one dose of IV ketamine at 1.0 mg/kg.
Drug: Ketamine · Device: Electroencephalogram (EEG)
Participants undergoing surgery for otolaryngeal cancer will be randomized to receive one dose of IV saline/placebo.
Drug: Placebo · Device: Electroencephalogram (EEG)
Ketamine will be administered intravenously after administration of general anesthesia and prior to the first surgical incision.
Placebo will be administered intravenously after administration of general anesthesia and prior to the first surgical incision.
Also known as: Saline Solution
A processed EEG device will be used during the surgical procedure to gather raw EEG data for off line analysis among patients developing post-operative delirium.
Change in Confusion Assessment Method fo Intensive Care Unit (CAM-ICU) Delirium Score
The CAM-ICU assesses four features: 1) acute change or fluctuation in mental status from baseline, 2) inattention, 3) altered level of consciousness, and 4) disorganized thinking. The measure reports whether a participant meets criteria for delirium by summing the number of features answered as "present". Feature 1 plus 2 and either 3 or 4 present = delirium positive. Results are expressed as number of participants with or without delirium at each time frame.
Time frame: Baseline (Up to 30 minutes after PACU arrival), Post Operative (PACU discharge up to 6 hours)
Change in Behavioral Pain Scale (Non-Intubated) Score
The Behavioral Pain Scale. Scores range from 3 (no pain) to 12 (maximum pain).
Time frame: Post Operation (Up to 6 Hours), Post Operation Day 0
Change in Pain Level Assessed by the Visual Analog Scale (VAS) Score
Scores range from 0 (no pain) to 10 (worst pain).
Time frame: Baseline, Post Surgery (PACU), Post surgery (POD 0), Post surgery (POD 1), Post surgery (POD 2), Post surgery (POD 3), Post surgery (follow up visit - Up to 6 weeks)
Change in Mini Cog Score
The Mini-Cog is a 3-minute instrument that can increase detection of cognitive impairment. A score ranging from 0-2 indicates positive screen for dementia. A score ranging from 3-5 indicates negative screen for dementia.
Time frame: Baseline, Post Surgery (Up to 6 Weeks)
Change in Mini-Mental Status Examination (MMSE) Score
The MMSE is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this (0-24), scores can indicate cognitive impairment.
Time frame: Baseline, Post Surgery (Up to 6 Weeks)
Change in Cognitive Failure Questionnaire (CFQ) Score
The CFQ is a 25-item self-report measure of failures in attention, perception, memory, and action. Participants are asked to indicate on a 5-point scale how often they have experienced each failure in the past months, from 0 (never) to 5 (very often). Scores range from 0 to 100 a higher score indicating more failures in attention.
Time frame: Baseline, Post Surgery (Up to 6 Weeks)
Post Operative Narcotics Use
The total amount of narcotics used measured in morphine milligram equivalents (MME).
Time frame: Post Intervention (Intraoperative), Post Intervention (POD 0), Post Intervention (POD 1),Post Intervention (POD 2),Post Intervention (POD 3), Post Intervention (Follow up visit-up to 6 weeks post intervention)
Associations of Intraoperative EEG Patterns With PACU Delirium
The investigators compared the relative beta power derived from the normalized power spectral density (PSD) in patients with and without PACU delirium (positive and negative delirium). Only a total of 38 EEGs with sufficient quality were analyzed. Results are expressed in percentage of cumulative power. A higher beta power correlates with worse outcome. Averages and standard deviations are shown.
Time frame: Intraoperative EEG and delirium during PACU stay
| Milestone | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Started | 21 | 26 | 24 |
| Completed | 21 | 24 | 23 |
| Not completed | 0 | 2 | 1 |
| Withdrew: Adverse event | 0 | 1 | 0 |
| Withdrew: Death | 0 | 1 | 0 |
| Withdrew: Physician decision | 0 | 0 | 1 |
The CAM-ICU assesses four features: 1) acute change or fluctuation in mental status from baseline, 2) inattention, 3) altered level of consciousness, and 4) disorganized thinking. The measure reports whether a participant meets criteria for delirium by summing the number of features answered as "present". Feature 1 plus 2 and either 3 or 4 present = delirium positive. Results are expressed as number of participants with or without delirium at each time frame.
| Participants | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Delirium CAM-ICU Score at PACU Arrival | 11 | 9 | 9 |
| No Delirium CAM-ICU Score at PACU Arrival | 6 | 13 | 10 |
| Delirium CAM-ICU Score at PACU Discharge | 6 | 5 | 2 |
| No Delirium CAM-ICU Score at PACU Discharge | 11 | 17 | 15 |
The Behavioral Pain Scale. Scores range from 3 (no pain) to 12 (maximum pain).
No measurements were reported for this outcome.
Scores range from 0 (no pain) to 10 (worst pain).
| units on a scale | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Baseline Pain Level assessed by the Visual Analog Scale (VAS) Score | 3.50 ± 3.25 | 4.36 ± 2.94 | 2.30 ± 2.88 |
| Pain Level assessed by the Visual Analog Scale (VAS) Score Post surgery (PACU) | 1.00 ± 2.45 | 2.56 ± 3.28 | 1.63 ± 3.11 |
| Pain Level assessed by the Visual Analog Scale (VAS) Score Post surgery (POD 0) | 4.76 ± 3.86 | 4.22 ± 3.24 | 3.62 ± 3.74 |
| Pain Level assessed by the Visual Analog Scale (VAS) Score Post surgery (POD 1) | 3.93 ± 2.76 | 3.72 ± 2.55 | 3.52 ± 2.42 |
| Pain Level assessed by the Visual Analog Scale (VAS) Score Post surgery (POD 2) | 2.47 ± 2.52 | 2.81 ± 2.51 | 3.38 ± 2.62 |
| Pain Level assessed by the Visual Analog Scale (VAS) Score Post surgery (POD 3) | 3.08 ± 2.94 | 3.35 ± 2.15 | 3.41 ± 2.20 |
| Pain Level assessed by the Visual Analog Scale Score Post surgery (follow up visit - Up to 6 weeks) | 2.3 ± 2.58 | 3.09 ± 2.68 | 3.00 ± 2.60 |
The Mini-Cog is a 3-minute instrument that can increase detection of cognitive impairment. A score ranging from 0-2 indicates positive screen for dementia. A score ranging from 3-5 indicates negative screen for dementia.
| Participants | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Baseline Mini Cog Score- Positive Screen | 2 | 5 | 6 |
| Baseline Mini Cog Score- Negative Screen | 18 | 20 | 18 |
| Mini Cog Score Post surgery (Up to 6 weeks) - Positive Screen | 3 | 0 | 3 |
| Mini Cog Score Post surgery (Up to 6 weeks) - Negative Screen | 17 | 23 | 17 |
The MMSE is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this (0-24), scores can indicate cognitive impairment.
| Participants | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Normal Baseline MMSE Score (25-30) | 18 | 22 | 22 |
| Cognitive Impairment Baseline MMSE Score (0-24) | 2 | 3 | 2 |
| Normal Post surgery (Up to 6 weeks) MMSE Score (25-30) | 17 | 23 | 16 |
| Cognitive Impairment Post surgery (Up to 6 weeks) MMSE Score (0-24) | 3 | 0 | 4 |
The CFQ is a 25-item self-report measure of failures in attention, perception, memory, and action. Participants are asked to indicate on a 5-point scale how often they have experienced each failure in the past months, from 0 (never) to 5 (very often). Scores range from 0 to 100 a higher score indicating more failures in attention.
| score on a scale | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Baseline CFQ Score | 27 (21 to 38) | 34 (22 to 40) | 30 (21.5 to 38.5) |
| CFQ Score Post surgery (Up to 6 weeks) | 29 (23 to 35) | 30 (15 to 40) | 29 (23 to 37) |
The total amount of narcotics used measured in morphine milligram equivalents (MME).
| morphine milligram equivalents (MME) | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Post Intervention (Intraoperative) | 13.3 (6.7 to 13.33) | 13.3 (10.0 to 20.0) | 13.33 (8.75 to 16.00) |
| Post Intervention (POD 0) | 7.1 (0 to 11.9) | 6.67 (0 to 11.9) | 6.18 (3.3 to 15.1) |
| Post Intervention (POD 1) | 35 (10.7 to 57.7) | 41.5 (27.1 to 91.4) | 42.9 (25.7 to 51.4) |
| Post Intervention (POD 2) | 8.59 (2.0 to 53.8) | 25.7 (10.0 to 78.6) | 41.9 (17.3 to 51.4) |
| Post Intervention (POD 3) | 19.8 (0.0 to 40.8) | 34.3 (2.0 to 50.7) | 34.3 (17.1 to 44.9) |
| Post Intervention (Follow up visit-up to 6 weeks) | 0 (0 to 8.6) | 0 (0 to 38.4) | 0 (0 to 25.7) |
The investigators compared the relative beta power derived from the normalized power spectral density (PSD) in patients with and without PACU delirium (positive and negative delirium). Only a total of 38 EEGs with sufficient quality were analyzed. Results are expressed in percentage of cumulative power. A higher beta power correlates with worse outcome. Averages and standard deviations are shown.
| Percentage of cumulative power | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Positive Delirium for PACU | 10.0 ± 5.0 | 7.0 ± 5.0 | 7.0 ± 6.0 |
| Negative Delirium for PACU | 7.0 ± 1.0 | 5.0 ± 6.0 | 6.0 ± 4.0 |
Collected over The research team monitored subjects randomized and treated in the study for adverse events related to the research through the final study visit in the ENT clinic that occurred from 2 to 6 weeks post-operatively.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ketamine 0.5 mg/kg | 0/21 (0%) | 4/21 (19%) | 3/21 (14.3%) |
| Ketamine 1.0 mg/kg | 1/26 (3.8%) | 9/26 (34.6%) | 5/26 (19.2%) |
| Placebo | 0/24 (0%) | 2/24 (8.3%) | 4/24 (16.7%) |
| Event | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Respiratory FailureRespiratory, thoracic and mediastinal disorders | 0/21 | 3/26 | 0/24 |
| DeliriumNervous system disorders | 1/21 | 0/26 | 1/24 |
| Surgical wound dehiscenceMusculoskeletal and connective tissue disorders | 1/21 | 0/26 | 0/24 |
| DysphagiaGastrointestinal disorders | 1/21 | 0/26 | 0/24 |
| Exposed tendon of left forearm free flapMusculoskeletal and connective tissue disorders | 1/21 | 0/26 | 0/24 |
| Facial artery clotVascular disorders | 0/21 | 0/26 | 1/24 |
| StrokeNervous system disorders | 0/21 | 1/26 | 0/24 |
| Carotid injuryVascular disorders | 0/21 | 1/26 | 0/24 |
| Post-operative wound abscessMusculoskeletal and connective tissue disorders | 0/21 | 1/26 | 0/24 |
| Bilateral MCA; PCA transcortical acute infarctsNervous system disorders | 0/21 | 1/26 | 0/24 |
| Event | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo |
|---|---|---|---|
| Respiratory distressRespiratory, thoracic and mediastinal disorders | 0/21 | 0/26 | 2/24 |
| AgitationNervous system disorders | 1/21 | 2/26 | 0/24 |
| Transient left sided weaknessNervous system disorders | 1/21 | 0/26 | 0/24 |
| DepressionPsychiatric disorders | 1/21 | 0/26 | 0/24 |
| HallucinationsPsychiatric disorders | 0/21 | 0/26 | 1/24 |
| SomnolenceGeneral disorders | 0/21 | 0/26 | 1/24 |
| AnxietyPsychiatric disorders | 0/21 | 1/26 | 0/24 |
| RestlessnessGeneral disorders | 0/21 | 1/26 | 0/24 |
| HypertensionVascular disorders | 0/21 | 1/26 | 0/24 |
| Age, Continuous(years) | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Mean | 63.7 ± 8.6 | 64.6 ± 12.4 | 64.5 ± 11.5 | 64.3 ± 10.9 |
| Sex: Female, Male(Participants) | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Female | 9 | 8 | 8 | 25 |
| Male | 12 | 18 | 16 | 46 |
| Ethnicity (NIH/OMB)(Participants) | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 0 | 1 |
| Not Hispanic or Latino | 20 | 26 | 24 | 70 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 2 | 4 | 4 | 10 |
| White | 18 | 21 | 20 | 59 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 0 | 1 |
| Region of Enrollment(participants) | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Placebo | Total |
|---|---|---|---|---|
| United States | 21 | 26 | 24 | 71 |
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