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

Washington University School of Medicine32 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Postoperative Depression

Interventions

KetamineDRUG

NMDA antagonist

Normal salineDRUG

IV fluid acting as a placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 14 days after the intervention

Secondary Outcomes

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.

Data from ClinicalTrials.gov

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