Inpatient Single Dose Interventions for Alcohol Use Disorder

Study Overview
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Brief Summary
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Every year, alcohol use disorder (AUD) generates millions of emergency department (ED) visits and hospital admissions, costing the U.S. health sector over $90 billion. These hospital admissions are critical opportunities to start patients on addiction pharmacotherapy, but factors like medication non-adherence and post-discharge relapse contribute to frequent re-admissions. Two single-dose interventions are well suited to facilitate treatment retention and prevent re-admissions due to their prolonged, adherence-independent effects: extended-release (XR) naltrexone injection and intravenous (IV) ketamine infusion. These have not been thoroughly investigated in the hospital setting among high-utilizer, safety-net populations. Therefore, the investigators aim to: Test the feasibility of randomizing hospitalized patients (n=45-60, age 18-65) with multiple AUD-related admissions to treatment with either extended-release (XR) naltrexone, intravenous (IV) ketamine, or no single-dose medication, all with enhanced linkage to care. Feasibility outcomes such as recruitment rate, patient acceptability, post-discharge follow-up rate, and adverse events will help to identify key lessons for a future comparative effectiveness study. Estimate the 30-day re-admission rate for patients randomized to treatment with XR naltrexone, with IV ketamine, or no single-dose medication, all with enhanced linkage to care. The investigators hypothesize that the re-admission rate will be lower for each of the two single-dose medication groups than for the linkage-alone group.

Official Title
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Single-dose Interventions to Reduce Re-admissions for Hospitalized Patients With Refractory Alcohol Use Disorder: A Randomized Pilot Feasibility Study.

Conditions
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Alcohol Use Disorder, Severe

Intervention / Treatment
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* Drug: Naltrexone 380 MG
* Drug: Ketamine Hydrochloride
* Behavioral: Enhanced linkage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 1+ alcohol-related* admission(s) or emergency department visit(s) in past 12 mo. Has insurance (public or private) Seen by inpatient addiction consult service Exclusion Criteria: Known or suspected active COVID-19 infection Hepatic: AST/ALT >5x upper-limit of normal, decompensated liver failure Renal: Glomerular filtration rate <30ml/min Cardiovascular: History of acute coronary syndrome, cerebrovascular event, hypertensive crisis, known cardiomyopathy Known elevated intracranial pressure Thrombocytopenia (<50/microliter) Active moderate/severe withdrawal (based on hospital withdrawal protocol) Active delirium (alcohol-related or otherwise) Already enrolled in study XR naltrexone or IV ketamine in last 30 days Known intolerance to naltrexone or ketamine Other active severe substance use disorder (tobacco, cannabis excluded) Pregnant or breast-feeding, or planning. Opioids: chronic, recent (<24h), or anticipated Unstable psychiatric illness (active psychosis, active suicidality) Moving from region within 30-days of discharge Discharge to acute/residential treatment Involuntary hold

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XR Naltrexone<br>Participants will receive a single dose of extended-release, injectable naltrexone prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. | Drug: Naltrexone 380 MG<br>* XR naltrexone to be given once prior to hospital discharge<br>Behavioral: Enhanced linkage<br>* Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up<br>|
| Experimental: IV Ketamine<br>Participants will receive a single dose of intravenous ketamine (0.5mg/kg over 40 minutes) prior to hospital discharge, in addition to enhanced linkage to follow-up addiction care. | Drug: Ketamine Hydrochloride<br>* IV ketamine infusion to be given once prior to hospital discharge<br>Behavioral: Enhanced linkage<br>* Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up<br>|
| Active Comparator: Linkage<br>Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care. | Behavioral: Enhanced linkage<br>* Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate (%) of 30-day hospital re-admission | Binary outcome: any all-cause hospitalization ascertained by chart review (our EHR includes records from several local hospitals) | Within 30 days of index hospital discharge. The enrollment period is 12 months. | 
| Feasibility - recruitment rate (# per month) | Number of participants recruited per month during the enrollment period | The enrollment period is 12 months | 
| Feasibility - follow-up rate (%) | Percentage of patients who presented to 1 week follow-up appointment | The enrollment period is 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average within-subject difference in readiness-to-change (SOCRATES-8A score) | Within-subject differences in readiness to change between inpatient enrollment and outpatient follow-up. | Follow-up planned to be within one week of discharge | 
| Rate (%) of 30-day emergency department visit | Binary outcome: any all-cause ED visit ascertained by chart review | Within 30 days of index hospital discharge. The enrollment period is 12 months. | 
| Rate (%) of urine Ethyl Glucuronide (EtG) at follow-up | Obtained by urine EtG at outpatient follow-up | Follow-up planned to be within one week of discharge. The enrollment period is 12 months. | 
| Rate (%) of self-reported binge drinking since discharge | Self reported at outpatient follow-up, ascertained by Timeline Follow-Back Method. | Follow-up planned to be within one week of discharge. The enrollment period is 12 months. |