The numerator will include all patients who are randomized to receive either ketamine or placebo. The denominator will include all patients who are approached by the research to evaluated eligibility and offer consent.
Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial
Brief Summary
This protocol describes a feasibility trial that will evaluate the feasibility of conducting a full-scale phase 3 trial testing the hypothesis that a postoperative sustained, low-dose ketamine infusion can prevent postoperative depressive symptoms when administered to a targeted population of neurosurgical patients with a history of depression.
Intervention / Treatment
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Ketamine (DRUG)NMDA antagonist
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Normal saline (DRUG)IV fluid acting as a placebo
Condition or Disease
- Postoperative Depression
Phase
Study Design
| Study type: | INTERVENTIONAL |
|---|---|
| Status: | Completed |
| Study results: | No Results Available |
| Enrollment: | 32 (ACTUAL) |
| Allocation: | Randomized |
| Primary Purpose: | Prevention |
MaskingQUADRUPLE:
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Clinical Trial Dates
| Start date: | Apr 25, 2022 | ACTUAL |
|---|---|---|
| Primary Completion: | Mar 08, 2023 | ACTUAL |
| Completion Date: | Mar 08, 2023 | ACTUAL |
| Study First Posted: | Feb 10, 2022 | ACTUAL |
| Last Updated: | Apr 27, 2023 |
Sponsors / Collaborators
Lead Sponsor:
Washington University School of Medicine
Responsible Party:
N/A
This protocol describes a feasibility trial that will evaluate the feasibility of conducting a full-scale phase 3 trial. Both the feasibility trial and the full-scale trial will follow a randomized, placebo-controlled, double-blinded, parallel design. The trial will follow a superiority design. This trial will take place at a single site (Washington University in St. Louis School of Medicine/Barnes-Jewish Hospital).
Following extubation, patients will be randomized to the intervention (ketamine group) or to control (control group). Patients in the ketamine group will receive a bolus of ketamine 0.5 mg/kg intravenously over 10 minutes, followed by an infusion at 0.3 mg/kg/h for an additional 2 hours 50 minutes. Patients in the control group will receive an equal volume of normal saline. Patients, research staff performing assessments, and research staff performing data analysis will be blinded to treatment allocation.
Following extubation, patients will be randomized to the intervention (ketamine group) or to control (control group). Patients in the ketamine group will receive a bolus of ketamine 0.5 mg/kg intravenously over 10 minutes, followed by an infusion at 0.3 mg/kg/h for an additional 2 hours 50 minutes. Patients in the control group will receive an equal volume of normal saline. Patients, research staff performing assessments, and research staff performing data analysis will be blinded to treatment allocation.
Participant Groups
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Following surgery and extubation, patients will receive ketamine 0.5 mg/kg over 10 minutes followed by an infusion of 0.3 mg/kg/h for 2 hours 50 minutes.
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Following surgery and extubation, patients will receive normal saline at an equal rate to that used in the ketamine arm.
Eligibility Criteria
| Sex: | All |
|---|---|
| Minimum Age: | 18 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
Inclusion Criteria:
1. Able to provide written, informed consent
2. Aged 18 or older
3. Scheduled for non-ambulatory surgery scheduled to last at least 2 hours at Barnes-Jewish Hospital
4. Past medical history of depression, defined as one or more of the following criteria
1. Previous diagnosis by a psychiatrist or primary care physician in an outpatient or inpatient setting, by patient report or chart documentation
2. Prescription of an oral antidepressant by a psychiatrist or primary care physician for a mood disorder
Exclusion Criteria:
1. Bipolar depression
2. Concurrent use of a medication contraindicated with ketamine
3. Emergent surgery
4. Known or suspected elevation in intracranial pressure
5. Current subarachnoid hemorrhage
6. Carotid endarterectomy or arteriovenous malformation repair
7. Allergy to ketamine
8. Any condition in which a significant elevation of blood pressure would constitute a serious hazard (e.g., aortic dissection, pheochromocytoma)
9. Known history of dementia
10. Pregnancy or lactation
11. Inability to converse in English
12. Concurrent enrollment in another interventional trial
1. Able to provide written, informed consent
2. Aged 18 or older
3. Scheduled for non-ambulatory surgery scheduled to last at least 2 hours at Barnes-Jewish Hospital
4. Past medical history of depression, defined as one or more of the following criteria
1. Previous diagnosis by a psychiatrist or primary care physician in an outpatient or inpatient setting, by patient report or chart documentation
2. Prescription of an oral antidepressant by a psychiatrist or primary care physician for a mood disorder
Exclusion Criteria:
1. Bipolar depression
2. Concurrent use of a medication contraindicated with ketamine
3. Emergent surgery
4. Known or suspected elevation in intracranial pressure
5. Current subarachnoid hemorrhage
6. Carotid endarterectomy or arteriovenous malformation repair
7. Allergy to ketamine
8. Any condition in which a significant elevation of blood pressure would constitute a serious hazard (e.g., aortic dissection, pheochromocytoma)
9. Known history of dementia
10. Pregnancy or lactation
11. Inability to converse in English
12. Concurrent enrollment in another interventional trial
Primary Outcomes
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-
The numerator will include all participants who receive the study medication for at least 2 of the planned 3 hours. The denominator will include all participants who are randomized to receive either ketamine or the placebo.
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Depression will be measured using the Montgomery-Asberg Depression Rating Scale (MADRS) at pre-operative baseline and on post-infusion days 1, 2, 4, 7, and 14. The numerator will include all patients with MADRS scores documented at all 6 time points. The denominator will include all participants who are randomized to receive either ketamine or the placebo.
Secondary Outcomes
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Depression will be measured using the Montgomery-Asberg Depression Rating Scale (MADRS) at pre-operative baseline and on post-infusion days 1, 2, 4, 7, and 14. For each randomized participant, the difference in MADRS score on post-infusion day 4 and at the preoperative baseline visit will be calculated. Participants with missing MADRS scores at either time point will be excluded. (No imputation of MADRS scores will be performed.) The distribution of delta MADRS scores in the population will be assessed for normality using visual analysis of histograms and using the Kolmogorov-Smirnoff test. If the delta MADRS scores are normally distributed, then the mean delta scores in the two groups will be compared using a two-sample t-test. If the delta MADRS scores are not normally distributed, then the median delta scores in the two groups will be compared using a Wilcoxon rank sum test.
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Electroencephalograms (EEG) will be captured using the Dreem headband (DREEM, Rhythm, New York, NY), a consumer-grade wireless device using dry electrodes. EEG will be captured overnight before surgery. Additional data collection using the Dreem headband will occur during the study medication infusion, the night following the study medication infusion, and the night following post-infusion day 1. The delta sleep ratio (DSR) will be defined as the ratio of slow wave activity (SWA = 1-4 Hz) during the first non-rapid eye movement (NREM) epoch to SWA during the second NREM epoch.
More Details
| NCT Number: | NCT05233566 |
|---|---|
| Other IDs: | 202201107 |
| Study URL: | https://clinicaltrials.gov/study/NCT05233566 |
Last updated: Sep 29, 2023