Clinical trial NCT05468840: Study of IV Ketamine for Emergency Department Treatment of Adolescent Suicidal Ideation
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Suicidal Ideation
Keywords: ketamine
emergency department
pediatrics
Lead sponsor: University of Ottawa
Sponsor class: OTHER
First posted: 2022-07-21
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria

1. Responds "yes" to ASQ questionnaire 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)
3. Age 12 to 17 years, inclusive
4. Medically clear, as judged by the treating physician
5. Speaks English or French

Exclusion Criteria

1. Acute intoxication
2. Previously enrolled in the current study or 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:

   1. Known allergy or hypersensitivity to ketamine by patient history
   2. History of cerebrovascular accident (stroke or aneurysm)
   3. History of elevated intracranial pressure or idiopathic intracranial hypertension
   4. Significant hypertension requiring daily medication
   5. Severe cardiac decompensation
7. On a Form 1
8. Requires physical or chemical restraint
9. History of violence while in hospital
10. Assessment by a mental health practitioner during the current ED visit prior to study enrollment
11. Pregnant or breastfeeding

Primary outcomes:
measure: Feasibility of the study as measured by the percentage of eligible of patients able to complete the study protocol.
timeFrame: Baseline
Secondary outcomes:
measure: Baseline distribution of responses to the first 5 questions of Beck Scale for Suicidal Ideation (SSI5)
timeFrame: Baseline
measure: Baseline distribution of responses to the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MARDS10)
timeFrame: Baseline
measure: Baseline distribution of responses to the suicide item (#9) from the Beck Depression Index (BDI9).
timeFrame: Baseline
measure: 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).
timeFrame: Baseline
measure: Blinding assessment
timeFrame: Baseline
measure: Treatment efficacy measured by the Beck Scale for Suicidal Ideation (SSI5)
timeFrame: 40 minutes post treatment start
measure: Treatment efficacy measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MARDS10)
timeFrame: 40 minutes post treatment start
measure: Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9)
timeFrame: 40 minutes post treatment start
measure: Treatment durability measured by the Beck Scale for Suicidal Ideation (SSI5)
timeFrame: 80 minutes, 120 minutes, 24 hours, and seven days post treatment start
measure: Treatment durability measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MARDS10)
timeFrame: 80 minutes, 120 minutes, 24 hours, and seven days post treatment start
measure: Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9)
timeFrame: 80 minutes, 120 minutes, 24 hours, and seven days post treatment start
measure: Admission to Hospital
timeFrame: 18 months
measure: Length of Stay in Hospital
timeFrame: 18 months
measure: Revisits to the ED
timeFrame: 18 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: CHEO
state: Ontario
Study officials:
References: