Inpatient Single Dose Interventions for Alcohol Use Disorder

Early Phase 1

Completed

Conditions: Alcohol Use Disorder, Severe

Interventions: Drug: Ketamine Hydrochloride
Drug: Naltrexone 380 MG
Behavioral: Enhanced linkage

Registration Number: NCT04562779

Lead Sponsor: Denver Health and Hospital Authority

Brief Summary: 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:

1. 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.

2. 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
XR Naltrexone	Enhanced linkage	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.
IV Ketamine	Ketamine Hydrochloride	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.
XR Naltrexone	Naltrexone 380 MG	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.
Linkage	Enhanced linkage	Participants will receive no single-dose addiction medication prior to hospital discharge, but will receive enhanced linkage to follow-up addiction care.
IV Ketamine	Enhanced linkage	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.

Primary Outcome Measures

Name	Time	Method
Feasibility - Recruitment Rate (# Per Month)	The enrollment period is 12 months	Number of participants recruited per month during the enrollment period
Feasibility - Follow-up Rate (%)	14 days	Percentage of patients who presented to follow-up appointment within 14 days
Rate (%) of 30-day Hospital Re-admission	Within 30 days of index hospital discharge. The enrollment period is 12 months.	Binary outcome: any all-cause hospitalization ascertained by chart review (our EHR includes records from several local hospitals). Note that it is not dependent on study completion, so it is analyzed by intent to treat.

Secondary Outcome Measures

Name	Time	Method
Rate (%) of 30-day Emergency Department Visit	Within 30 days of index hospital discharge. The enrollment period is 12 months.	Binary outcome: any all-cause ED visit ascertained by chart review