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

• ClinicalTrials.gov Identifier: NCT05233566
• Recruitment Status: Recruiting
• First Posted: February 10, 2022
• Last Update Posted: May 2, 2022
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Bradley Fritz, Washington University School of Medicine

Tracking Information

• First Submitted Date: February 3, 2022
• First Posted Date: February 10, 2022
• Last Update Posted Date: May 2, 2022
• Actual Study Start Date: April 25, 2022
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2022)

• Fraction of Approached Patients Who Enroll and Are Randomized [ Time Frame: 3 days after surgery ]
  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 [ Time Frame: 3 days after surgery ]
  The numerator will include all participants who receive the study medication for at least 7 of the planned 8 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 [ Time Frame: 14 days after the intervention ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 3, 2022)

• Depressive Symptoms on Day 4 [ Time Frame: 4 days after the intervention ]
  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 [ Time Frame: 2 days after intervention ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ketamine for Postoperative Avoidance of Depressive Symptoms: The K-PASS Feasibility Trial
• Official Title: 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.

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).

On the day 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 7 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Postoperative Depression

Intervention

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

Study Arms

• Experimental: Ketamine Arm
  On the first day 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 7 hours 50 minutes.
  Intervention: Drug: Ketamine
• Placebo Comparator: Control Arm
  On the first day following surgery and extubation, patients will receive normal saline at an equal rate to that used in the ketamine arm.
  Intervention: Drug: Normal saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 3, 2022): 32
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Able to provide written, informed consent
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 or older
4. Scheduled for a surgery with planned intensive care unit admission at Barnes-Jewish Hospital

5. 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. Outpatient antipsychotic medication use
3. Emergent surgery
4. Known or suspected elevation in intracranial pressure
5. 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. Outpatient use of an anticonvulsant with significant sodium channel activity: carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenytoin, riluzole, and valproic acid
10. Known history of dementia
11. Pregnancy or lactation
12. Inability to converse in English
13. Concurrent enrollment in another interventional trial
14. Postoperative mechanical ventilation continuing past 07:00am on postoperative day 3

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bradley A Fritz, MD; 314-273-3453; bafritz@wustl.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05233566
• Other Study ID Numbers: 202201107
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bradley Fritz, Washington University School of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Washington University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Washington University School of Medicine
• Verification Date: April 2022