Clinical trial NCT06366334: 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: RECRUITING
Phase: NA
Conditions: Suicidal Ideation
Suicidal Ideas
Lead sponsor: Children's Hospital of Eastern Ontario
Sponsor class: OTHER
First posted: 2024-04-15
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 Ask Suicide Screening Question (ASQ) #5 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 (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 an involuntary psychiatric hold
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

Primary outcomes:
measure: Proportion of eligible participants who 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 (MADRS10)
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: Assessment of blinding
timeFrame: Baseline
measure: Treatment efficacy measured by the Beck Scale for Suicidal Ideation (SSI5)
timeFrame: 40 minutes after the beginning of the infusion
measure: Treatment efficacy measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10)
timeFrame: 40 minutes after the beginning of the infusion
measure: Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9)
timeFrame: 40 minutes after the beginning of the infusion
measure: Treatment durability measured by the Beck Scale for Suicidal Ideation (SSI5)
timeFrame: 40, 80, 120 minutes after the beginning of the infusion as well as 24 hours and 7 days post enrollment
measure: Treatment durability measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10)
timeFrame: 40, 80, 120 minutes after the beginning of the infusion as well as 24 hours and 7 days post enrollment
measure: Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9)
timeFrame: 40, 80, 120 minutes after the beginning of the infusion as well as 24 hours and 7 days post enrollment
measure: Admission to Hospital
timeFrame: Enrollment visit
measure: Length of Stay in Hospital
timeFrame: 30 days post enrollment
measure: ED revisits
timeFrame: 30-days post enrollment
Other outcomes:
measure: Safety Outcome 1: Clinically significant tachycardia
timeFrame: Enrollment visit
measure: Safety Outcome 2: Clinically significant hypertension
timeFrame: Enrollment visit
measure: Safety Outcome 3: Vomiting
timeFrame: Enrollment visit
measure: Safety Outcome 4: Dissociation
timeFrame: During the infusion
measure: Safety Outcome 5: Death
timeFrame: 30-days post enrolment
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital Of Eastern Ontario
state: Ontario
Study officials:
affiliation: CHEO
name: Tyrus Crawford, BA
role: STUDY_DIRECTOR
References: