Clinical trial NCT02478489: Alcohol Disorder hOsPital Treatment Trial
Official title: Oral v. Injection Naltrexone in Hospital: Comparative Effectiveness for Alcoholism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heavy Drinking
Alcohol Dependence
Alcohol Use Disorder
Keywords: alcohol
heavy drinking
naltrexone
hospital
alcohol use disorder
alcohol dependence
comparative effectiveness
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2015-06-23
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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

Primary outcomes:
measure: Change in Percent Heavy Drinking Days (%HDDs) Over the Past 30 Days From Baseline to 3 Month Follow-up, Assessed Using the Timeline Follow-Back
timeFrame: Baseline, 3 months
Secondary outcomes:
measure: Acute Care Hospital Utilization
timeFrame: 3 months
Other outcomes:
measure: Medication Adherence
timeFrame: 1, 2 and 3 months
measure: Alcohol Consequences Via Questionnaire
timeFrame: 3 months
measure: Alcohol Use Disorder-related Treatment Utilization Via Questionnaire and Health Records
timeFrame: 3 months
measure: Cost Via Utilization Questionnaire, Health Records and Estimates From Local and National Sources
timeFrame: 3 and 12 months
Locations:
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
Study officials:
affiliation: Boston University
name: Richard Saitz, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: