Study of IV Ketamine for Emergency Department Treatment of Adolescent Suicidal Ideation

Suicidal Ideation Clinical Trial

— KSI  

Official title:

A Double Blinded, Randomized, Placebo Controlled, Parallel Arm Pilot Trial of Intravenous Ketamine for Emergency Department Treatment of Suicidal Ideation in a Pediatric Population.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06366334
• Other study ID #: 23/02E
• Status: Recruiting
• Phase: N/A
• Start date: January 15, 2024
• Est. completion date: September 30, 2024

Study information

• Verified date: April 2024
• Source: Children's Hospital of Eastern Ontario
• Contact: Maala Bhatt, MD
• Phone: 6137377600
• Email: mbhatt[@]cheo.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Approximately 20% of Canadian adolescents experience thoughts of suicide, or suicidal ideation (SI), and suicide is the second leading cause of death among Canadians aged 15-19 years. The emergency department at CHEO sees approximately four patients per day with SI. Even though this is a medical emergency, there are no fast-acting treatments available. Ketamine is a medication that is commonly used to safely sedate children who require painful procedures in the emergency department. For nearly ten years, intravenous ketamine has also been shown to rapidly reduce SI in adults. However, ketamine as a treatment for SI has never been studied in adolescents. The primary study objective is to pilot a clinical trial that investigates intravenous ketamine to emergently treat SI in adolescents. If intravenous ketamine can relieve symptoms of SI for youth, this would have tremendous effects on patients and would dramatically change how physicians treat adolescent mental health emergencies. If ketamine is effective for several weeks, as it is in adults, it will help temporize patients until they receive more long-term psychiatric care. At the system level, it has the potential to reduce emergency visits and lengthy admissions. The investigators feel that the results of this study will be generalizable to pediatric centres across Canada and beyond.

Description:

Suicidal ideation (SI) is a common and often severe cause of morbidity in adolescents. Patients frequently present to the emergency department (ED) with severe and distressing thoughts of self-harm or suicide, and yet, there is currently no acute therapeutic intervention to offer them. The standard of care for patients who do not require admission is to discharge them home with resources for websites, apps, or telephone help lines. These interactions fail to address the underlying suicidal thoughts and leave patients, families and providers feeling very dissatisfied. Medications are nearly never initiated in the ED and patients who are already taking anti-depressants experience a very slow therapeutic onset, and often with unfavourable side effects that make medication compliance difficult and sometimes impossible. For nearly ten years, intravenous ketamine has been shown to be an efficacious acute therapy in adult patients with suicidal ideation. A single dose of intravenous (IV) ketamine can rapidly reduce the severity of suicidal ideation by moderate to large effect sizes (Cohen's d = 0.5-0.8) during an ED visit, in an adult population. However, it has never been studied in a pediatric population. The study primary objective is to determine the feasibility of conducting a trial that investigates the efficacy of IV ketamine to reduce suicidal ideation in adolescents in the pediatric emergency department. If intravenous ketamine can rapidly alleviate the severity of SI for adolescents, this would have tremendous effects on patients and families and dramatically change how ED physicians treat pediatric mental health emergencies. It would increase patient safety, reduce patient distress, morbidity, possibly mortality and alleviate family stress. If the therapeutic effect of ketamine is maintained for several days, as it is in adults, it will help temporize patient symptoms while they are connected with more long-term psychiatric care. At the system level, it may reduce rates of ED visits and, often lengthy, admissions to hospital. The investigators feel that the results of this study will be generalizable to pediatric centres across Ontario, Canada and beyond.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Responds "yes" to ASQ at triage, which asks; "Are you having thoughts of killing yourself right now?"

2. Moderate to severe suicidal ideation, defined as score = 3 on the first 5 questions of the Beck Scale for Suicidal Ideation (SSI5)46 (Appendix A.2)

3. Age 12 to 17 years, inclusive

4. Medically clear (deemed fit for participation in the trial), as judged by the treating physician. Minimum criteria required to be deemed medically clear are: a) No evidence of serious physical injury requiring urgent intervention b) No evidence of acute ingestion requiring monitoring, blood tests, imaging or ECG or in the context of acute ingestion they have satisfied the requisite number of hours of post-ingestion monitoring with no further need for intervention.

Exclusion Criteria:

1. Acute intoxication from any substance, including alcohol

2. Previously enrolled in the current study or currently enrolled in another clinical trial

3. History of intellectual disability or autism spectrum disorder by patient/parent report

4. Active, or history of, psychosis or psychotic disorder

5. History of non-psychiatric neurologic disorder (e.g., epilepsy)

6. Any of the following contraindications to ketamine based on the drug monograph: a) Known allergy or hypersensitivity to ketamine by patient history b) History of cerebrovascular accident (stroke or aneurysm) c) History of elevated intracranial pressure or idiopathic intracranial hypertension d) Significant hypertension requiring daily medication e) Severe cardiac decompensation

7. On a Form 1

8. Requires physical or chemical restraint

9. History of violence while in hospital

10. Pregnant or breastfeeding

11. Received opioids in the 2-hours prior to study screening

Related Conditions & MeSH terms

• Emergencies
• Suicidal Ideas
• Suicidal Ideation

Intervention

Drug:
• Ketamine Hydrochloride
See arm description
• Normal saline
See arm description

Locations

Country	Name	City	State
Canada	Children's Hospital Of Eastern Ontario	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Eastern Ontario

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety Outcome 1: Clinically significant tachycardia	Requires intervention by the treating team	Enrollment visit
Other	Safety Outcome 2: Clinically significant hypertension	Requires intervention by the treating team	Enrollment visit
Other	Safety Outcome 3: Vomiting	Vomiting during or after the infusion	Enrollment visit
Other	Safety Outcome 4: Dissociation	CADSS - total score of 6 or more OR 4 on any single question AND unresponsive with unstable vital signs	During the infusion
Other	Safety Outcome 5: Death	Death from any cause within 30 days following enrolment	30-days post enrolment
Primary	Proportion of eligible participants who complete the study protocol	This is a feasibility measure; we will report the number of patients who are screened for participation, are eligible, eligible and consent, complete the intervention, complete study follow-up	Baseline
Secondary	Baseline distribution of responses to the first 5 questions of Beck Scale for Suicidal Ideation (SSI5)	Estimates of central tendency (mean) and variance (standard deviation) from participant responses to the SSI5 at baseline will be measured and reported. These parameters will aid with sample size estimates for the larger definitive trial.; The first 5 questions of Beck Scale for Suicidal Ideation (SSI5) is a five item questionnaire scored from 0 to 10, with higher scores indicating more severe suicidal ideation.	Baseline
Secondary	Baseline distribution of responses to the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10)	Estimates of central tendency (mean) and variance (standard deviation) from participant responses to the MADRS10 at baseline will be measured and reported. These parameters will aid with sample size estimates for the larger definitive trial.; The MADRS is a 10 item, 6-point, depression scale. Item 10 rates suicidal ideation from 0 (Enjoys life or takes it as it comes), to 6 (Explicit plans for suicide when there is an opportunity. Active preparations for suicide) with higher scores indicating more severe suicidal ideation.	Baseline
Secondary	Baseline distribution of responses to the suicide item (#9) from the Beck Depression Index (BDI9).	Estimates of central tendency (mean) and variance (standard deviation) from participant responses to the BDI9 at baseline will be measured and reported. These parameters will aid with sample size estimates for the larger definitive trial.; The Beck Depression Inventory is a 21 item depression questionnaire. Item 9 rates suicidal ideation from 0 (I don't have thoughts of killing myself) to 3 (I would kill myself if I had the chance) with higher scores indicating more severe suicidal ideation.	Baseline
Secondary	Baseline pragmatic assessment of the first 5 questions of the Beck Scale for Suicidal Ideation (SSI5), the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10), and the suicide item (#9) from the Beck Depression Index (BDI9).	Pragmatic assessment of the tool validity by asking each participant, which of the three tools best captures how they are feeling at baseline.	Baseline
Secondary	Assessment of blinding	Blinding adequacy will be measured by asking each participant which intervention they think they received at the end of the 40 minute study drug infusion.	Baseline
Secondary	Treatment efficacy measured by the Beck Scale for Suicidal Ideation (SSI5)	Change in suicidal ideation severity from baseline at the end of the 40-minute medication infusion will be measured using SSI5.; The first 5 questions of Beck Scale for Suicidal Ideation (SSI5) is a five item questionnaire scored from 0 to 10, with higher scores indicating more severe suicidal ideation.	40 minutes after the beginning of the infusion
Secondary	Treatment efficacy measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10)	Change in suicidal ideation severity from baseline at the end of the 40-minute medication infusion will be measured using MADRS10.; The MADRS is a 10 item, 6-point, depression scale. Item 10 rates suicidal ideation from 0 (Enjoys life or takes it as it comes), to 6 (Explicit plans for suicide when there is an opportunity. Active preparations for suicide) with higher scores indicating more severe suicidal ideation.	40 minutes after the beginning of the infusion
Secondary	Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9)	Change in suicidal ideation severity from baseline at the end of the 40-minute medication infusion will be measured using BDI9.; The Beck Depression Inventory is a 21 item depression questionnaire. Item 9 rates suicidal ideation from 0 (I don't have thoughts of killing myself) to 3 (I would kill myself if I had the chance) with higher scores indicating more severe suicidal ideation.	40 minutes after the beginning of the infusion
Secondary	Treatment durability measured by the Beck Scale for Suicidal Ideation (SSI5)	The durability of a treatment effect on suicidal ideation will be measured by SSI5 at 80 minutes, 120 minutes, 24 hours, and seven days post treatment start.; The first 5 questions of Beck Scale for Suicidal Ideation (SSI5) is a five item questionnaire scored from 0 to 10, with higher scores indicating more severe suicidal ideation.	40, 80, 120 minutes after the beginning of the infusion as well as 24 hours and 7 days post enrollment
Secondary	Treatment durability measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10)	The durability of a treatment effect on suicidal ideation will be measured by MADRS10 at 80 minutes, 120 minutes, 24 hours, and seven days post treatment start.; The MADRS is a 10 item, 6-point, depression scale. Item 10 rates suicidal ideation from 0 (Enjoys life or takes it as it comes), to 6 (Explicit plans for suicide when there is an opportunity. Active preparations for suicide) with higher scores indicating more severe suicidal ideation.	40, 80, 120 minutes after the beginning of the infusion as well as 24 hours and 7 days post enrollment
Secondary	Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9)	The durability of a treatment effect on suicidal ideation will be measured by BDI9 at 80 minutes, 120 minutes, 24 hours, and seven days post treatment start.; The Beck Depression Inventory is a 21 item depression questionnaire. Item 9 rates suicidal ideation from 0 (I don't have thoughts of killing myself) to 3 (I would kill myself if I had the chance) with higher scores indicating more severe suicidal ideation.	40, 80, 120 minutes after the beginning of the infusion as well as 24 hours and 7 days post enrollment
Secondary	Admission to Hospital	Proportion of patients who require hospital admission at the enrolment ED visit	Enrollment visit
Secondary	Length of Stay in Hospital	The mean and standard deviation of length of hospital stay for patients admitted at the enrollment visit	30 days post enrollment
Secondary	ED revisits	Proportion of patients who have an ED visit(s) for mental health complaints within 30 days following enrolment	30-days post enrollment