Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics (Keta4SI)

• ClinicalTrials.gov Identifier: NCT04955470
• Recruitment Status: Recruiting
• First Posted: July 8, 2021
• Last Update Posted: November 7, 2022
• Sponsor: University of British Columbia
• Information provided by (Responsible Party): Quynh Doan, University of British Columbia

Tracking Information

• First Submitted Date: June 21, 2021
• First Posted Date: July 8, 2021
• Last Update Posted Date: November 7, 2022
• Actual Study Start Date: June 1, 2022
• Estimated Primary Completion Date: November 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2021)

• Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 90 minutes post infusion ]
  The CSSR-S is 6-point scale that measures SI severity via clinical interviews, ranging from 1 (wish to be dead) to 5 (suicidal intent with plan). Adolescents who deny any SI receive a 0. The distribution of "yes" responses on questions 3, 4, or 5 will be assessed from baseline. Higher scores indicate greater SI severity.
• Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 90 minutes post infusion ]
  The MADRS is a 10-item, 6-point scale that screens for depressive symptoms in adults via clinical interviews. A self-reported version (MADRS-self assessment) which has been validated in adolescents will be used, but only the final item that is specific to SI (item 10) will be asked. The distribution of scores from 0 to 6 will be assessed from baseline. Higher scores indicate greater SI severity.
• Pragmatic questionnaire [ Time Frame: 90 minutes post infusion ]
  The pragmatic questionnaire is a brief, one sentence question designed to assess change in SI. Participants will be asked "How suicidal do you feel on a scale of 0 to 10?". The distribution of scores from 0 to 10 will be assessed from baseline. Higher scores indicate greater SI severity.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 17, 2022)

• Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 24 hours ]
  The CSSR-S is 6-point scale that measures SI severity via clinical interviews, ranging from 1 (wish to be dead) to 5 (suicidal intent with plan). Adolescents who deny any SI receive a 0. The distribution of "yes" responses on questions 3, 4, or 5 will be assessed from baseline. Higher scores indicate greater SI severity.
• Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
  The MADRS is a 10-item, 6-point scale that screens for depressive symptoms in adults via clinical interviews. A self-reported version (MADRS-self assessment) which has been validated in adolescents will be used, but only the final item that is specific to SI (item 10) will be asked. The distribution of scores from 0 to 6 will be assessed from baseline. Higher scores indicate greater SI severity.
• Pragmatic questionnaire [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
  The pragmatic questionnaire is a brief, one sentence question designed to assess change in SI. Participants will be asked "How suicidal do you feel on a scale of 0 to 10?". The distribution of scores from 0 to 10 will be assessed from baseline. Higher scores indicate greater SI severity.
• Blinding assessment [ Time Frame: 90 minutes post infusion ]
  The proportion of participants and research personnel that correctly identify treatment arm allocation.
• Enrolment rate [ Time Frame: 28-days ]
  Proportion of eligible patients that consent to participate, and proportion of participants that are lost to follow-up at 7-, 14-, 21-, and 28-days.
• Demographics [ Time Frame: 28-days ]
  Demographics of eligible patients who decline to participate in the study.
• Drug reactions [ Time Frame: 28-days ]
  Incidence and frequency of side effects and adverse events.

Original Secondary Outcome Measures (submitted: July 6, 2021)

• Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
  The CSSR-S is 6-point scale that measures SI severity via clinical interviews, ranging from 1 (wish to be dead) to 5 (suicidal intent with plan). Adolescents who deny any SI receive a 0. The distribution of "yes" responses on questions 3, 4, or 5 will be assessed from baseline. Higher scores indicate greater SI severity.
• Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
  The MADRS is a 10-item, 6-point scale that screens for depressive symptoms in adults via clinical interviews. A self-reported version (MADRS-self assessment) which has been validated in adolescents will be used, but only the final item that is specific to SI (item 10) will be asked. The distribution of scores from 0 to 6 will be assessed from baseline. Higher scores indicate greater SI severity.
• Pragmatic questionnaire [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
  The pragmatic questionnaire is a brief, one sentence question designed to assess change in SI. Participants will be asked "How suicidal do you feel on a scale of 0 to 10?". The distribution of scores from 0 to 10 will be assessed from baseline. Higher scores indicate greater SI severity.
• Blinding assessment [ Time Frame: 90 minutes post infusion ]
  The proportion of participants and research personnel that correctly identify treatment arm allocation.
• Enrolment rate [ Time Frame: 28-days ]
  Proportion of eligible patients that consent to participate, and proportion of participants that are lost to follow-up at 7-, 14-, 21-, and 28-days.
• Demographics [ Time Frame: 28-days ]
  Demographics of eligible patients who decline to participate in the study.
• Drug reactions [ Time Frame: 28-days ]
  Incidence and frequency of side effects and adverse events.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics
• Official Title: Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics: a Pilot Randomized Controlled Trial
• Brief Summary: Suicide is a leading cause of death for children and adolescents. Since warning signs of suicide and links to precipitating events differ between age groups, suicide can be difficult to predict. As a result, children often seek care for suicidal ideation (SI) in the emergency department (ED) where a limited number of treatment options exist. Current psychotherapies and pharmacotherapies, such as antidepressants, provide benefit over weeks or months and thus limits their effective application in the ED. Consequently, when there is an imminent threat to the child's safety, the typical management solution is to admit the patient to a safe environment and hopefully de-escalate over time. To address a more rapid-onset treatment option for SI, a number of studies in adults have suggested that a single, sub-anesthetic dose of intravenous ketamine can rapidly reduce depression and SI severity. These results are promising, but large-scale trials are needed to determine if ketamine is a safe and effective treatment for acute suicidality in the pediatric population. This approach has the benefit of working rapidly, avoiding involuntary hospitalizations, and protecting patients from self-harm until they can be connected to longer term mental health resources. This study will compare the use of intravenous ketamine to both active and placebo controls in children 10 to 17 years of age presenting to the pediatric ED for SI. The primary objective of this pilot trial is to explore the adequacy and range of three instruments measuring suicidality and to determine the sample size required for a large definitive randomized control trial. This larger trial will be used to estimate the effectiveness of intravenous ketamine for reducing SI in children in the pediatric ED. The secondary objectives are to assess study feasibility and optimize study procedures. Given very few side effects reported in adult studies and the relatively benign nature of those reported, the investigators do not expect any major safety concerns in the study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Suicidal Ideation

Intervention

• Drug: Ketamine Injectable Solution
  A 10 mg/mL solution of ketamine will be infused over a 40 minute period at a dose of 0.05mg/kg.
• Drug: Midazolam Injectable Solution
  A 5 mg/mL solution of midazolam will be infused over a 40 minute period at a dose of 0.02 mg/kg.
• Drug: Normal Saline 0.9% Injectable Solution
  A 0.9% normal saline solution will be infused over a 40 minute period.

Study Arms

• Experimental: Intravenous ketamine
  Infusion of 0.5 mg/kg of ketamine, at maximum dose of 40 mg, over 40 minutes.
  Intervention: Drug: Ketamine Injectable Solution
• Active Comparator: Intravenous midazolam
  Infusion of 0.03 mg/kg of midazolam, at maximum dose of 2 mg, over 40 minutes.
  Intervention: Drug: Midazolam Injectable Solution
• Placebo Comparator: Intravenous saline
  Infusion of 0.9% saline over 40 minutes.
  Intervention: Drug: Normal Saline 0.9% Injectable Solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 6, 2021): 96
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2024
• Estimated Primary Completion Date: November 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

The study will enroll children and adolescents presenting with SI in the paediatric ED.

Inclusion Criteria:

1. 10 to 17 years of age
2. Respond "yes" to either question 1 (Passive Ideation) or 2 (Active Ideation) on the C-SSRS
3. Respond "yes" to either questions 3 (Method), 4 (Intent), or 5 (Plan) on the C-SSRS
4. Deemed acceptable and appropriate for admission to the on-site Child and Adolescent Psychiatry Emergency (CAPE) unit by a pediatric psychiatrist
5. Successful completion of Capacity to Assent.
6. Normal vital signs for age and a normal neurological exam (no focal deficits or abnormalities), as per attending clinician

Exclusion Criteria:

1. History of benzodiazepine or ketamine use in the past 3 months (ample wash out period)
2. Lifetime history of ketamine or benzodiazepine use disorder
3. Previous diagnosis of schizophrenia or active psychosis as per the treating physician
4. Lifetime history of schizoaffective disorder
5. Current hypomania, mania, mixed state
6. Clinically unstable, requires resuscitation or admission to a medical ward for stabilizing therapy (i.e., intensive care unit.)
7. History of cerebrovascular accident, uncontrolled seizure disorder, increased intracranial pressure
8. Uncontrolled hypertension, low or labile blood pressure, severe cardiac decompensation
9. Moderate to severe hepatic/renal impairment
10. Intoxicated or delirious
11. Suspected or confirmed pregnancy or women who are breastfeeding
12. Known allergy or sensitivity to ketamine and/or midazolam or any component in the formulation.
13. Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction
14. Inability to understand spoken and/or written English without the use of an interpreter
15. Previous enrollment in this study
16. No parent/guardian present.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Karly Stillwell; (604) 875-2345 ext 3691; kstillwell@bcchr.ca

Contact: Tatsuma Hind, BSc; txhind@student.ubc.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT04955470
• Other Study ID Numbers: H21-01433
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Quynh Doan, University of British Columbia
• Original Responsible Party: Same as current
• Current Study Sponsor: University of British Columbia
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Quynh Doan, PhD MHSc MD; University of British Columbia

• PRS Account: University of British Columbia
• Verification Date: November 2022