Alcohol Disorder hOsPital Treatment Trial

NCT ID: NCT02478489

Last Updated: 2021-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-10-31

Brief Summary

The specific aims of this pragmatic randomized controlled trial are to compare initiating injectable extended release naltrexone (XR-NTX) or oral naltrexone (PO-NTX) at the time of discharge from a medical hospitalization for patients with alcohol use disorder (AUD) on: 1) alcohol consumption and consequences, and 2) acute healthcare utilization (including hospital readmission and emergency visits) and cost-effectiveness. In exploratory analyses, the investigators will assess moderators of medication effects including demographic, behavioral, and genetic factors.

Detailed Description

Hospitalization for medical illness is a unique and missed opportunity for intervention for alcohol use disorders (AUDs). Referrals can help link patients from hospitals to alcohol treatment. But most patients return to heavy drinking after hospital discharge and do not follow-up with alcohol treatment, risking hospital readmission. Pharmacotherapy has efficacy for AUD, but adherence to these medications is poor. Furthermore, these medications are rarely prescribed in general medical settings, during or after hospitalization. Beginning treatment for AUD during a hospitalization for medical illness could broaden the reach of effective treatment and is likely to be more effective than delaying treatment until a specialist visit or treatment program entry. Hospital discharge is a time of both risk (i.e., for drinking and non-adherence to medical care) and opportunity (i.e., to begin alcohol treatment and complete medical treatments). Interventions that work quickly and improve adherence could improve medical and alcohol-related outcomes.

Oral naltrexone (PO-NTX), and the more-costly-per-dose long-acting injectable extended release naltrexone (XR-NTX) are Food and Drug Administration (FDA)-approved efficacious treatments for AUD. The XR-NTX half-life is 5-10 days and is dosed monthly, whereas the PO-NTX half-life is 13 hours and is dosed daily. The longer half-life of XR-NTX translates into patients receiving effective pharmacotherapy for a longer time without having to adhere to a daily dose. Thus, although more costly per dose, greater effectiveness could mean overall reduced costs of care (including alcohol-related health consequences and healthcare utilization). Despite potential differences in costs and patient preferences, PO-NTX and XR-NTX have not been directly compared in a randomized controlled trial (RCT), they have not been studied as treatments at medical hospital discharge, and their effectiveness in real world practice settings compared with standard care is unknown.

This trial is significant because it will address the clinically relevant comparative effectiveness question and lead to greater adoption of the most effective and cost-effective approach for treating AUD with pharmacotherapy in general hospitals.

Conditions

Heavy Drinking; Alcohol Dependence; Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Extended-release injectable naltrexone (XR-NTX)

Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks.

Group Type: EXPERIMENTAL

Extended-release injectable naltrexone (XR-NTX)

Intervention Type: DRUG

injectable naltrexone

Oral naltrexone (PO-NTX)

Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking.

Group Type: ACTIVE_COMPARATOR

Oral naltrexone (PO-NTX)

Intervention Type: DRUG

oral naltrexone

Interventions

Oral naltrexone (PO-NTX)

oral naltrexone

Intervention Type: DRUG

Extended-release injectable naltrexone (XR-NTX)

injectable naltrexone

Intervention Type: DRUG

Other Intervention Names

Revia; Vivitrol

Eligibility Criteria

Inclusion Criteria

• Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 alcohol use disorder (AUD) (assessed using Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS))
• ≥1 heavy drinking episodes (≥5 standard drinks [4 for women] in a day) in 30 days prior to hospitalization*
• Inpatient on a hospital general medical service
• Adult (age 18 years or greater)
• Ability to speak English (fluency)
• ≥2 contact persons*

Exclusion Criteria

• Pregnancy (urine testing if childbearing potential)
• Currently breast-feeding
• Urine expanded panel drug test (dipstick) positive for opiates, semi-synthetic or synthetic opioids
• Opioid use (self-report and verification in medical record) in past 7 days for long-acting opioids
• Opioid use in past 24 hours for short-acting opioids
• Discharge prescription for opioids
• Future need for opioids for an anticipated painful event or surgery
• Known hypersensitivity to NTX
• Acute severe psychiatric illness (currently suicidal or psychotic)
• Cognitive dysfunction that precludes informed consent or research assistant (RA) assessment that subject cannot understand interview questions
• Alanine aminotransferase or aspartate aminotransferase >5 times the upper limit of normal
• Acute hepatitis
• Liver failure
• Known severe thrombocytopenia (<50,000)
• Coagulopathy
• Coagulation disorder
• Body habitus that precludes intramuscular injection
• Plans to leave the Boston area in less than one year
• Enrollment in a research study which involves taking a pharmaceutical agent that is expected to interact with naltrexone

[*criteria not changed since study start; change reflects correction of typo]

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Boston University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Saitz, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Boston University

Locations

Boston Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Magane KM, Dukes KA, Fielman S, Palfai TP, Regan D, Cheng DM, Lee H, Kraemer KL, Bullard MJ, Chen CA, Samet JH. Oral vs Extended-Release Injectable Naltrexone for Hospitalized Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Intern Med. 2025 Jun 1;185(6):635-645. doi: 10.1001/jamainternmed.2025.0522.

Reference Type: DERIVED

PMID: 40257810 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01AA021335

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-32911

Identifier Type: -

Identifier Source: org_study_id