Ketamine for OUD and Suicidal Ideation in the ED

Study Overview
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Brief Summary
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This is a pilot, double-blind, placebo-controlled randomized clinical trial of individuals with opioid use disorder (OUD) with suicidal ideation in the emergency department (ED) to receive either a single infusion of ketamine 0.8mg/kg (n=25) or saline placebo (n=25). The primary aim is to evaluate the safety of the ketamine treatment. The secondary aim is to determine the preliminary efficacy of opioid- and suicide-related outcomes.

Detailed Description
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Individuals with opioid use disorder (OUD) seeking medical care in the emergency department (ED) will be first evaluated as per usual clinical care by the ED staff, including any acute medical treatment for overdose or any other acute medical issues needing treatment. For those who endorse suicidal ideation, after medical clearance, the standard medical care will involve the evaluation of patients by the psychiatry consult service in the ED. Patients evaluated by psychiatry who require further behavioral health care and do not have acute medical issues remain in the ED awaiting admission to an inpatient psychiatry unit or other linkages to care. Potential participants will be approached after the psychiatry evaluation is complete and a decision has been made to keep the patients in the ED for continued psychiatric care or admit them medically. After applying the full inclusion and exclusion criteria, those who remain eligible will be randomized to receive in a double-blind fashion either a single infusion of ketamine (0.8mg/kg) or a saline placebo. Safety assessments will be conducted during and after the receipt of ketamine or placebo, and at follow-up assessments after discharge from the emergency department of the hospital following inpatient psychiatric treatment.

Official Title
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Ketamine for the Treatment for Opioid Use Disorder and Suicidal Ideation in the Emergency Department

Conditions
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Opioid Use Disorder, Suicidal Ideation

Intervention / Treatment
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* Drug: Ketamine
* Other: Saline Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaking adults aged 18 and above Diagnosed with DSM5 opioid use disorder, moderate or severe Endorsing suicidal ideation sufficiently severe to meet criteria for referral to an inpatient psychiatric facility or a crisis stabilization unit Any prior history of an opioid overdose Medically cleared Exclusion Criteria: Any psychotic disorder, bipolar disorder, active homicidally Inability to perform consent due to impaired mental status, including substance intoxication Systolic blood pressure persistently elevated above 160mmHg, or heart rate >130bmp, in the ED Clinical Opioid Withdrawal Scale (COWS) score of 12 or greater History of hypersensitivity to ketamine, or experience of emergence reaction History of any illicit or recreational use of ketamine in the past 12 months Receipt of ketamine treatment for depression in the past 3 months History of DSM5 hallucinogen use disorder, intracranial mass or bleed, porphyria, thyrotoxicosis, seizure disorder other than from alcohol withdrawal, liver cirrhosis, obstructive lung disease, or sleep apnea History within 6 months of thoracic surgery, lung cancer, head trauma, stroke, or myocardial infarction Liver dysfunction with LFTs >3x upper normal limit Current use of medications with known drug-drug interactions with ketamine (i.e., St. John's Wort, theophylline, opioid analgesics other than buprenorphine and methadone for the treatment OUD, CNS depressants other than benzodiazepines or phenobarbital) Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>This arm will receive ketamine (n=25) | Drug: Ketamine<br>* The intervention will consist of a single infusion of ketamine in the ED at a dose of 0.8mg/kg over 40 minutes.<br>|
| Placebo Comparator: Saline Placebo<br>This arm will receive the saline placebo (n=25) | Other: Saline Solution<br>* The placebo will be a 0.9% saline solution administered over 40 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Less Illicit Opioid Use | For illicit opioid use, the outcome is the proportion of abstinent days during the 28-day period after discharge from the ED or the inpatient psychiatric unit, assessed using the self-report Timeline Follow Back (TLFB). The TLFB is a gold-standard calendar method to assess substance use in the prior 28 days. | 28 days after being discharged from inpatient unit or emergency department. | 
| Lower Suicidal Ideation | The Scale for Suicidal Ideation (SSI), which is a 19-item scale, will be used to measure the severity of suicidal ideation. | 7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department. | 
| Lower Suicidal Ideation | For suicidal ideation, the Columbia Suicide Severity Rating Scale (C-SSRS), which is a 5-item tool, will be used to assess suicidal ideation. | 7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department. | 
| Incidence of Serious Adverse Events (SAE) | The primary safety outcome is the incidence of serious adverse events (SAE) defined as hypertensive urgency (SBP>180mmHg or DBP>110mmHg) or tachycardia (HR>130bmp). Vital signs will be monitored throughout the ketamine administration. | From the beginning on the infusion, every 15 minutes throughout infusion, and at the end of the infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Withdrawal | Opioid withdrawal will be measured using the Clinical Opioid Withdrawal Scale (COWS). Scoring: 5-12 = mild 13-24 = moderate 25-36 = moderately severe >36 = severe withdrawal | Assessed daily while the participant remains in the ED, starting with the day that the ketamine/placebo infusion occurs until the discharge date. | 
| Days to Relapse | Days to Relapse will be assessed using the self-report Timeline Follow Back (TLFB). The TLFB is a gold-standard calendar method to assess substance use in the prior 28 days. | 7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department. | 
| Percentage of Addiction Treatment Engagement | Evaluating whether the patient is engaged or not in treatment, such as meeting their primary care physician or addiction specialist. | 28 days after being discharged from inpatient unit or emergency department. | 
| Urine Toxicology Result for Ketamine | The urine drug screen result (positive or negative) for ketamine will be assessed. | 28 days after being discharged from inpatient unit or emergency department. | 
| Urine Toxicology Result for Opioids | The urine drug screen result (positive or negative) for opioids will be assessed. | 28 days after being discharged from inpatient unit or emergency department. | 
| Emergence of Psychiatric Adverse Effects | The CADSS is scale with 23 subject-rated items and 5 items scored by an observer. Items are divided into 3 components-depersonalization, derealization, and amnesia. | 28 days after being discharged from inpatient unit or emergency department. | 
| Emergence of Psychiatric Adverse Effects | The PRISE is a patient self-report tool used to qualify side effects in the following domains: gastrointestinal, heart, skin, nervous system, eyes/ears, genital/urinary, sleep, sexual functioning, and other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether the symptoms are tolerable or distressing | 28 days after being discharged from inpatient unit or emergency department. | 
| Emergence of Psychiatric Adverse Effects | The BPRS is a 24-item scale to assess the severity of psychotic symptoms. | 28 days after being discharged from inpatient unit or emergency department. | 
| Craving for Opioids | The Opioid Craving Questionnaire (3-item scale) will assess opioid craving. Each question assesses opioid craving with answer choices ranging from 0 (not at all) to 10 (extremely strong) or 0 (not at all) to 10 (I'm sure I would use opiates). A higher score for each question indicates higher opioid cravings. | 7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department. | 
| Craving for Ketamine | The Ketamine Craving Questionnaire (3-item scale) will assess ketamine craving. Each question assesses ketamine craving with answer choices ranging from 0 (not at all) to 10 (extremely strong) or 0 (not at all) to 10 (I'm sure I would use ketamine). A higher score for each question indicates higher ketamine cravings. | 7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department. |