Postoperative DepressionPhase 3K-PASSNCT05233566
Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial
A Phase 3 study testing Ketamine and Normal saline in people with Postoperative Depression, run by Washington University School of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Depression
- What is being tested?
- Ketamine and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2022to 8 Mar 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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.
Read the 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.
- Conditions
- Postoperative Depression
- Being tested
- Ketamine, Normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
NMDA antagonist
Normal salineDrug
IV fluid acting as a placebo
| Study group | Role | What they receive |
|---|---|---|
| Ketamine Arm | Experimental | 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. Receives: Drug: Ketamine |
| Control Arm | Placebo comparator | Following surgery and extubation, patients will receive normal saline at an equal rate to that used in the ketamine arm. Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 team to evaluated eligibility and offer consent.
Measured: 3 days after surgery
Fraction of Randomized Patients Who Complete the Study Infusion
The numerator will include all participants who received the entire study medication infusion as planned.
The denominator will include all participants who are randomized to receive either ketamine or the placebo.
Measured: 3 days after surgery
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. MADRS scores range 0 to 60, with higher scores representing worse depression.
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.
Measured: 14 days after the intervention
Secondary outcomes (4)
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. MADRS scores range 0 to 60, with higher scores representing worse depression.
The distribution of MADRS scores in the population will be assessed for normality using visual analysis of histograms and using the Kolmogorov-Smirnoff test. If the MADRS scores are normally distributed, then the mean scores in the two groups on post-infusion day 4 will be compared using linear regression, adjusting for preoperative score. If the MADRS scores are not normally distributed, then the median delta scores in the two groups will be compared using median regression, adjusting for preoperative score.
Participants with missing MADRS scores at either time point (preoperative baseline or post-infusion day 4) will be excluded.
Measured: 4 days after the intervention
Delta Sleep Ratio on Night 1 Following Study Medication
Electroencephalograms (EEG) will be captured during sleep using the Dreem headband (DREEM, Rhythm, New York, NY), a consumer-grade wireless device using dry electrodes. Sleep stages (e.g., non-rapid eye movement [NREM], rapid eye movement, wakefulness) will be detected using the Dreem headband's built-in automated sleep scoring algorithm. During each time epoch, slow wave activity will be defined as the EEG power in the range 1-4 Hz. The delta sleep ratio (DSR) will be defined as the ratio of slow wave activity during the first NREM epoch to slow wave activity during the second NREM epoch.
Because it is a ratio, the DSR is a dimensionless number. In normal sleep, slow wave activity is greatest at the beginning of the night and decreases throughout the night. Therefore, higher DSR values reflect a more normal sleep architecture.
Measured: 2 days after intervention
Delta Sleep Ratio on Night 1 Following Study Medication - Stratified by Sex
NIH-required analysis.
Electroencephalograms (EEG) will be captured during sleep using the Dreem headband (DREEM, Rhythm, New York, NY), a consumer-grade wireless device using dry electrodes. Sleep stages (e.g., non-rapid eye movement [NREM], rapid eye movement, wakefulness) will be detected using the Dreem headband's built-in automated sleep scoring algorithm. During each time epoch, slow wave activity will be defined as the EEG power in the range 1-4 Hz. The delta sleep ratio (DSR) will be defined as the ratio of slow wave activity during the first NREM epoch to slow wave activity during the second NREM epoch.
Because it is a ratio, the DSR is a dimensionless number. In normal sleep, slow wave activity is greatest at the beginning of the night and decreases throughout the night. Therefore, higher DSR values reflect a more normal sleep architecture.
Measured: 2 days after intervention
Delta Sleep Ratio on Night 1 Following Study Medication - Stratified by Race
NIH-required analysis.
Electroencephalograms (EEG) will be captured during sleep using the Dreem headband (DREEM, Rhythm, New York, NY), a consumer-grade wireless device using dry electrodes. Sleep stages (e.g., non-rapid eye movement [NREM], rapid eye movement, wakefulness) will be detected using the Dreem headband's built-in automated sleep scoring algorithm. During each time epoch, slow wave activity will be defined as the EEG power in the range 1-4 Hz. The delta sleep ratio (DSR) will be defined as the ratio of slow wave activity during the first NREM epoch to slow wave activity during the second NREM epoch.
Because it is a ratio, the DSR is a dimensionless number. In normal sleep, slow wave activity is greatest at the beginning of the night and decreases throughout the night. Therefore, higher DSR values reflect a more normal sleep architecture.
Measured: 2 days after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2022
- Study start25 Apr 2022
- Primary completion8 Mar 2023
- Study completion8 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postoperative DepressionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bradley Fritz, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05233566
- Sponsor's protocol ID
- 202201107
- Acronym
- K-PASS
- Status last verified
- Mar 2024
- First submitted
- 3 Feb 2022
- Last updated
- 21 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Fritz BA, Tellor Pennington BR, Dalton C, Horan C, Palanca BJA, Schweiger JA, Griffin L, Tumwesige W, Willie JT, Farber NB. Ketamine for postoperative avoidance of depressive symptoms: the K-PASS feasibility randomised trial. BJA Open. 2023 Dec 15;9:100245. doi: 10.1016/j.bjao.2023.100245. eCollection 2024 Mar.
PubMed 38179107Fritz BA, Tellor Pennington BR, Palanca BJA, Schweiger JA, Willie JT, Farber NB. Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial. F1000Res. 2022 May 11;11:510. doi: 10.12688/f1000research.121529.1. eCollection 2022.
PubMed 37483552