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

Postoperative Depression Clinical Trial

— K-PASS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05233566
• Other study ID #: 202201107
• Status: Completed
• Phase: Phase 3
• Start date: April 25, 2022
• Est. completion date: March 8, 2023

Study information

• Verified date: March 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 with a history of depression.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 8, 2023
• Est. primary completion date: March 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Postoperative Depression

Intervention

Drug:
• Ketamine
NMDA antagonist
• Normal saline
IV fluid acting as a placebo

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 days after surgery
Primary	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.	3 days after surgery
Primary	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.	14 days after the intervention
Secondary	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.	4 days after the intervention
Secondary	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.	2 days after intervention