IM Ketamine vs Midazolam for Suicidal ER Patients

Study Overview
=================
Brief Summary
-----------------
Rising US suicide rates and the increased risk of suicide among persons who visit an emergency department (ED) for suicidality make the ED an important site for interventions to prevent suicide. There is no approved treatment for rapid relief of suicidal thoughts although clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with inexpensive, generic, sub-anesthetic ketamine. We propose a clinical trial of intramuscular ketamine in depressed ED patients with high-risk suicidality, which if successful would support a novel, easy-to-use, scalable intervention for busy emergency clinicians to implement.

Detailed Description
-----------------
Rising US suicide rates and the increased risk of suicide among persons who visit an emergency department (ED) for suicidality make the ED an important site for interventions to prevent suicide. Clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with inexpensive, generic, subanesthetic ketamine. We have received NIMH R01 funding to conduct a clinical trial of intramuscular (IM) ketamine in unipolar or bipolar depressed adults who present to the CUIMC psychiatric ED with suicidality severe enough to require inpatient hospitalization as judged by ED clinical staff. Clinical staff will ask potentially eligible patients if they would like to learn more about the study, and if so, a research assistant (RA) will describe the study to the patient and perform a basic eligibility screen. Key exclusions are unstable medical problems, substance abuse, psychosis, and further detail is provided in the Inclusion/Exclusion criteria. Participants (N=90) who enroll will undergo baseline clinical ratings, brief cognitive testing, and then be randomized, double-blind, in a 2:1 ratio to a single IM injection of ketamine (n=60) or midazolam comparator (n=30). Vital signs and clinical state will be monitored until injection effects subside (approximately 2 hrs). Blood samples will be drawn at 60 minutes and 90 minutes postinjection to assay ketamine level and a genetic sample will be stored. All participants will then be admitted to the 9GN inpatient unit for standard clinical treatment with periodic research follow-up ratings through 4 weeks post-discharge from hospital. Ongoing outpatient treatment will be arranged by the inpatient clinical team. Positive results from this trial would support a novel, easy-to-use, inexpensive, and scalable intervention for busy emergency clinicians to implement.

Official Title
-----------------
IM Ketamine vs Midazolam for Suicidal ER Patients

Conditions
-----------------
Depression, Unipolar, Depression, Bipolar, Suicidal Ideation

Intervention / Treatment
-----------------
* Drug: Ketamine hydrochloride injection
* Drug: Midazolam injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: DSM5 unipolar or bipolar (I, II, or Unspecified) major depressive episode Presenting to emergency department and assessed by psychiatrist staff as needing inpatient treatment due to suicidality Participant agrees to voluntary inpatient psychiatric admission Beck Scale for Suicidal Ideation score of 4 or higher Exclusion Criteria: Substance use disorder in past 2 weeks Current psychosis or mania Intellectual disability Inadequate understanding of English and/or lack of capacity for informed consent Pregnancy or lactation Medical contraindication to ketamine or midazolam Unstable medical or neurological illness such as uncontrolled hypertension, significant cardiac arrhythmia, unstable cerebrovascular disease. Chronic, stable medical conditions such as controlled hypertension or diabetes will not be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>Ketamine hydrochloride 0.5 mg/kg IM single injection | Drug: Ketamine hydrochloride injection<br>* single IM injection of ketamine hydrochloride 0.5 mg/kg<br>|
| Active Comparator: midazolam<br>Midazolam 0.06 mg/kg IM single injection | Drug: Midazolam injection<br>* single IM injection of midazolam 0.06 mg/kg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for Suicidal Ideation (SSI) | Beck Scale for Suicidal Ideation clinician-rated version | 24 hours post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systematic Assessment for Treatment Emergent Events (SAFTEE) | Frequency of adverse events at 24 hours post-treatment | 24 hours post-treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
depression, suicidality, clinical trial, ketamine, midazolam