IM Ketamine vs Midazolam for Suicidal ER Patients

• ClinicalTrials.gov Identifier: NCT04640636
• Recruitment Status: Recruiting
• First Posted: November 23, 2020
• Last Update Posted: February 21, 2021
• Sponsor: New York State Psychiatric Institute
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Michael Grunebaum, MD, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: November 20, 2020
• First Posted Date: November 23, 2020
• Last Update Posted Date: February 21, 2021
• Actual Study Start Date: January 2, 2021
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2020)

Scale for Suicidal Ideation (SSI) [ Time Frame: 24 hours post-treatment ]

Beck Scale for Suicidal Ideation clinician-rated version

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2020)

Systematic Assessment for Treatment Emergent Events (SAFTEE) [ Time Frame: 24 hours post-treatment ]

Frequency of adverse events at 24 hours post-treatment

• 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: IM Ketamine vs Midazolam for Suicidal ER Patients
• Official Title: IM Ketamine vs Midazolam for Suicidal ER Patients
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Depression, Unipolar
• Depression, Bipolar
• Suicidal Ideation

Intervention

• Drug: Ketamine hydrochloride injection
  single IM injection of ketamine hydrochloride 0.5 mg/kg
• Drug: Midazolam injection
  single IM injection of midazolam 0.06 mg/kg

Study Arms

• Experimental: Ketamine
  Ketamine hydrochloride 0.5 mg/kg IM single injection
  Intervention: Drug: Ketamine hydrochloride injection
• Active Comparator: midazolam
  Midazolam 0.06 mg/kg IM single injection
  Intervention: Drug: Midazolam injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 20, 2020): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Meghan Enslow, BA; 646-774-7564; meghan.enslow@nyspi.columbia.edu

Contact: Michael Grunebaum, MD; 646-774-7573; michael.grunebaum@nyspi.columbia.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04640636
• Other Study ID Numbers: 8070; R01MH125155-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

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

• Plan to Share IPD: Yes
• Plan Description: All associated research findings published or provided to NIH, will be made readily available for research purposes to qualified individuals within the scientific community. All data will be made anonymous and available after written requests for data are submitted by such qualified individuals to the PI.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)

• Responsible Party: Michael Grunebaum, MD, New York State Psychiatric Institute
• Study Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Michael Grunebaum, MD; New York State Psychiatric Institute/Columbia University Irving Medical Center

• PRS Account: New York State Psychiatric Institute
• Verification Date: February 2021