Alcohol Disorder hOsPital Treatment Trial

Alcohol Use Disorder Clinical Trial

— ADOPT  

Official title:

Oral v. Injection Naltrexone in Hospital: Comparative Effectiveness for Alcoholism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02478489
• Other study ID #: H-32911
• Secondary ID: R01AA021335
• Status: Completed
• Phase: Phase 4
• Start date: June 2016
• Est. completion date: October 2020

Study information

• Verified date: June 2021
• Source: Boston University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 248
• Est. completion date: October 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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]

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Heavy Drinking

Intervention

Drug:
• Oral naltrexone (PO-NTX)
oral naltrexone
• Extended-release injectable naltrexone (XR-NTX)
injectable naltrexone

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Medication Adherence	High adherence to XR-NTX will be defined as administration of XR-NTX by the study nurse 3 times. Medium adherence will be defined as 1 or 2 injections. For PO-NTX, high adherence will be defined as participant self-report of taking PO-NTX for 90 out of the past 90 days at the 3 month study visit, and medium adherence as participant self-report of taking PO-NTX for 30-89 out of the past 90 days at the 3 month study visit (Form 90). We will also assess the presence of detectable beta-naltrexol to confirm reports of recent pill taking.	1, 2 and 3 months
Other	Alcohol Consequences Via Questionnaire	Alcohol consequences over the past 3 months will be measured by collecting participant self-report data via the Short Inventory of Problems (SIP-2R) at 3-month follow-up. The SIP-2R is a validated 15-item measure for assessing recent adverse consequences associated with alcohol use.	3 months
Other	Alcohol Use Disorder-related Treatment Utilization Via Questionnaire and Health Records	Alcohol use disorder-related treatment utilization over the past 90 days assessed at 3-month follow-up by the Form 90. Using the clinical data warehouse at one site (Boston Medical Center (BMC)) and statewide data, we will compare self-report to the utilization databases. But, self-report data will remain primary, with databases used to provide a descriptive frame of reference.	3 months
Other	Cost Via Utilization Questionnaire, Health Records and Estimates From Local and National Sources	Healthcare utilization cost data will be collected via the Form 90 for self-reported outpatient and emergency visits, hospitalizations, and specialty addiction treatment. Utilization episodes will be converted to costs by use of Medicare relative value units (RVUs) for acute inpatient care, Resource Based Relative Value System (RBRVS) units for Medicare reimbursement of outpatient visits, and the average daily rate for long-term care.	3 and 12 months
Primary	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	The primary alcohol use outcome will be change in percent heavy drinking days (%HDDs) from baseline to 3 month follow-up. %HDDs out of the past 30 days is assessed using the Timeline Follow-Back. %HDDs is the most likely (and most sensitive) to be affected by NTX and is clinically important (any reduction means less risk of harm). We chose self-report because biological testing is not sufficiently valid for detecting drinking levels and changes of clinical importance. The self-report tool is valid, particularly so when staff are well trained, and when the context for the subject is: they are informed they are being tested for consumption (breath alcohol and carbohydrate deficient transferrin (CDT), there are no consequences related to consumption levels, and that results are being recorded confidentially.	Baseline, 3 months
Secondary	Acute Care Hospital Utilization	Any acute hospital utilization (emergency department visit or inpatient stay) over the past 90 days assessed at 3-month follow-up by the Form 90. Self-report for short-term high impact, memorable health utilization such as emergency and hospital stays is valid and can measure utilization at any site. Using the clinical data warehouse at one site (Boston Medical Center (BMC)) and statewide data, we will compare self-report to the utilization databases. But, self-report data will remain primary, with databases used to provide a descriptive frame of reference.	3 months