Ketamine for the Treatment for Opioid Use Disorder and Suicidal Ideation in the Emergency Department
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Lower Suicidal Ideation
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
Participants will then be randomized in a double-blind fashion to receive either ketamine (0.8 mg/kg) or a matched volume saline placebo in the ED. Randomization will use a permuted block method58. The randomization ratio will be 1:1. A biostatistician will generate the randomization codes and provide the randomization list to the hospital's Investigational Drug Services (IDS). The study RA will contact IDS once the participant has signed informed consent and IDS staff will randomize participants. Both RA, study team and the clinical team will be blinded to the allocation.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •To be eligible, individuals must be/have:
- •English speaking adults aged 18 and above
- •Diagnosed with DSM5 opioid use disorder, moderate or severe, or clinically suspected opioid use disorder
- •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
- •Individuals with any of the following will be excluded:
- •Any psychotic disorder or active homicidally
- •Inability to perform consent due to impaired mental status
- •Current substance intoxication or current (or within the past 1-month) mania, hypomania, mixed-episode, or psychosis
- •Systolic blood pressure persistently elevated above 160mmHg, diastolic blood pressure greater than 100 mmHg, or heart rate >100bmp, 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 hypersensitivity to ondansetron or concurrently using apomorphine
- •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, or sleep apnea
- •Cardiac or EKG abnormalities based on history, physical examination or the baseline EKG
- •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, Central Nervous System (CNS) depressants other than benzodiazepines or phenobarbital)
- •Patients who are breastfeeding
- •ASA class 3 or greater or documented history of difficult airway in HER
- •Active exacerbation of COPD or asthma
- •Currently participating or anticipated to participate in a concurrent investigational clinical trial
- •High risk for adverse emotional or behavioral reaction based on the opinion of the study investigators, including evidence of a personality disorder
Arms & Interventions
Ketamine
This arm will receive ketamine (n=25)
Intervention: Ketamine (Drug)
Saline Placebo
This arm will receive the saline placebo (n=25)
Intervention: Saline Solution (Other)
Outcomes
Primary Outcomes
Lower Suicidal Ideation
Time Frame: 7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department.
For suicidal ideation, the Columbia Suicide Severity Rating Scale (C-SSRS), which is a 5-item tool, will be used to assess suicidal ideation.
Less Illicit Opioid Use
Time Frame: 28 days after being discharged from inpatient unit or emergency department.
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.
Incidence of Serious Adverse Events (SAE)
Time Frame: From the beginning on the infusion, every 15 minutes throughout infusion, and at the end of the infusion.
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.
Secondary Outcomes
- Opioid 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(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(28 days after being discharged from inpatient unit or emergency department.)
- Urine Toxicology Result for Ketamine(28 days after being discharged from inpatient unit or emergency department.)
- Urine Toxicology Result for Opioids(28 days after being discharged from inpatient unit or emergency department.)
- Emergence of Psychiatric Adverse Effects(28 days after being discharged from inpatient unit or emergency department.)
- Craving for Opioids(7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department.)
- Craving for Ketamine(7-day remote follow up; 14- day remote follow up; 28 days after being discharged from inpatient unit or emergency department.)
Investigators
Joji Suzuki, MD
Director, Division of Addiction Psychiatry
Brigham and Women's Hospital