Inpatient Single Dose Interventions for Alcohol Use Disorder

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

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder, Severe
• Intervention / Treatment: Drug: Naltrexone 380 MG; Behavioral: Enhanced linkage; Drug: Ketamine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XR Naltrexone; 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; XR naltrexone to be given once prior to hospital discharge; Behavioral: Enhanced linkage; Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up
Experimental: IV Ketamine; 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.	Behavioral: Enhanced linkage; Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up; Drug: Ketamine Hydrochloride; IV ketamine infusion to be given once prior to hospital discharge
Active Comparator: Linkage; 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; Includes in-hospital intake at outpatient addiction clinic plus contingency management related to follow-up

What is the study measuring?

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). Note that it is not dependent on study completion, so it is analyzed by intent to treat.	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 follow-up appointment within 14 days	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Narcotic Antagonists; Alcohol Deterrents; Ketamine; Naltrexone
• Other Study ID Numbers: 20-2008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No