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Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial (K-PASS)

Primary Purpose

Postoperative Depression

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Ketamine
Normal saline
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Postoperative Depression

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine Arm

Control Arm

Arm Description

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.

Following surgery and extubation, patients will receive normal saline at an equal rate to that used in the ketamine arm.

Outcomes

Primary Outcome Measures

Fraction of Approached Patients Who Enroll and Are Randomized
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.
Fraction of Randomized Patients Who Complete the Study Infusion
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.
Fraction of Randomized Patients with Depression Rating Scale Scores at All Specified Time Points
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 Outcome Measures

Depressive Symptoms on Day 4
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.
Delta Sleep Ratio
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.

Full Information

First Posted
February 3, 2022
Last Updated
April 27, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT05233566
Brief Title
Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial
Acronym
K-PASS
Official Title
Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
April 25, 2022 (Actual)
Primary Completion Date
March 8, 2023 (Actual)
Study Completion Date
March 8, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Depression

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ketamine Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm Description
Following surgery and extubation, patients will receive normal saline at an equal rate to that used in the ketamine arm.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Ketalar
Intervention Description
NMDA antagonist
Intervention Type
Drug
Intervention Name(s)
Normal saline
Intervention Description
IV fluid acting as a placebo
Primary Outcome Measure Information:
Title
Fraction of Approached Patients Who Enroll and Are Randomized
Description
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.
Time Frame
3 days after surgery
Title
Fraction of Randomized Patients Who Complete the Study Infusion
Description
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.
Time Frame
3 days after surgery
Title
Fraction of Randomized Patients with Depression Rating Scale Scores at All Specified Time Points
Description
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.
Time Frame
14 days after the intervention
Secondary Outcome Measure Information:
Title
Depressive Symptoms on Day 4
Description
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.
Time Frame
4 days after the intervention
Title
Delta Sleep Ratio
Description
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.
Time Frame
2 days after intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to provide written, informed consent Aged 18 or older Scheduled for non-ambulatory surgery scheduled to last at least 2 hours at Barnes-Jewish Hospital Past medical history of depression, defined as one or more of the following criteria Previous diagnosis by a psychiatrist or primary care physician in an outpatient or inpatient setting, by patient report or chart documentation Prescription of an oral antidepressant by a psychiatrist or primary care physician for a mood disorder Exclusion Criteria: Bipolar depression Concurrent use of a medication contraindicated with ketamine Emergent surgery Known or suspected elevation in intracranial pressure Current subarachnoid hemorrhage Carotid endarterectomy or arteriovenous malformation repair Allergy to ketamine Any condition in which a significant elevation of blood pressure would constitute a serious hazard (e.g., aortic dissection, pheochromocytoma) Known history of dementia Pregnancy or lactation Inability to converse in English Concurrent enrollment in another interventional trial
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

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Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial

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