Extended-Release vs. Oral Naltrexone Alcohol Treatment in Primary Care (X-ON)

Randomized, Open-label Clinical Trial of Extended-Release vs. Oral Naltrexone for Alcohol Treatment in Primary Care.

The proposed study is a pragmatic, randomized, open-label clinical trial of 24 weeks of XR-NTX vs. O-NTX using a COMBINE-adapted Medical Management primary care treatment model. 237 adults >18yo with alcohol dependence will be recruited from the community into treatment in public sector primary care settings. The primary outcome which powers this study is a dichotomous good clinical outcome defined by abstinence or moderate drinking, and as measured by the Timeline Follow-back and analyzed using an intention-to-treat approach among all randomized participants. Secondary outcomes include the incremental cost effectiveness of the two arms, differences between arms by continuous measures of alcohol intake (drinks/day, % days abstinent, time to first heavy drinking day, bio-markers), and the exploratory analysis of factors possibly associated with effectiveness, including gender, prior treatment abstinence, and mu opioid receptor (OPRM1) genotypes.

Specific Aim 1: Treatment Effectiveness. To evaluate the effectiveness of extended-release naltrexone (XR-NTX) vs. oral naltrexone (O-NTX) in producing a primary good clinical outcome, defined as abstinence or moderate drinking (≤2 drinks/day, men; ≤1 drink/day,women; and ≤2 heavy drinking occasions/month), during the final 20 of 24 weeks of primary care-based Medical Management for alcohol dependence. Hypothesis: The rate of this good clinical outcome will be approximately twice as great among participants receiving XR-NTX compared with those receiving O-NTX.

Specific Aim 2: Cost Effectiveness. To estimate the incremental cost effectiveness of XR-NTX vs. O-NTX,both in conjunction with primary care-based Medical Management. Hypothesis: XR-NTX treatment will be more cost effective than O-NTX.

Specific Aim 3: Patient-Level Predictors of Effectiveness. To identify patient-level characteristics associated with effectiveness in both arms.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence
• Intervention / Treatment: Drug: XR-NTX (Extended-Release Naltrexone); Drug: Oral Naltrexone (O-NTX)

Detailed Description

Rationale: Though integration of alcohol pharmacotherapy into primary care settings is receiving increasing emphasis and support, rigorous data to inform clinicians' treatment choice is lacking. The most recently FDA-approved alcohol treatment medication, an extended-release depot form of naltrexone (XR-NTX, Vivitrol®), could greatly simplify the medical home-centered alcohol treatment emphasized in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Clinician's Guide. Injected once a month, XR-NTX offers a long-acting and thus potentially more effective form of pharmacotherapy than oral naltrexone (O-NTX), which, despite the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) trial and systematic reviews supporting some efficacy, has been characterized by low rates of overall prescribing, poor adherence, suboptimal monthly refill and inadequate treatment retention. Yet while promising as an alternative to O-NTX, XR-NTX is substantially more expensive (~$1100 vs. ~$100 per month), and no head-to-head trials have compared the two forms of naltrexone. A comparative effectiveness approach is required to systematically evaluate the following key questions: In primary care settings, what is the relative clinical effectiveness of XR-NTX vs. O-NTX? What are the benefits and costs of XR-NTX relative to O-NTX? And can patient and system characteristics be identified to inform treatment choice to maximize the probability of successful outcome?

Implications: Despite several years of experience, the comparative effectiveness of XR-NTX compared to older alcohol medications remains uncertain, particularly in a mainstream, primary care treatment model that is generalizable and broadly accessible. Newer, novel, expensive medications for addiction disorders are historically greatly underutilized by primary care physicians. This study is innovative both as a 'head-to-head' evaluation of XR-NTX vs. O-NTX in primary care, and because expected participants will be primarily Medicaid-covered or uninsured persons who will not be excluded based on medical and psychiatric co-morbidities that often preclude participation in efficacy studies. If health insurance expansion, parity reforms, medical homes and accountable care organizations are to define primary care as a core alcohol treatment setting in the coming decade, exactly this type of study is required to guide treatment protocols and resource allocation. Ultimately, more widespread adoption of cost-effective alcohol pharmacotherapies will result in longer,healthier lives and lower costs.

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults, age ≥18 y.o.
• English- or Spanish- speaking and able to understand study procedures and provide full consent.
• DSM IV diagnosis of alcohol dependence as determined by study physician and DSM IV checklist.
• Endorses goal of abstinence, and is able to achieve alcohol abstinence without inpatient detoxification, per study physician.

Exclusion Criteria:

• Current opioid dependence and/or positive urine toxicology for extended opioids.
• Pregnancy or female planning conception.
• Allergy to naltrexone or the PGL XR-NTX formulation or diluent.
• Severe liver disease, liver failure, or liver function test levels greater than three times normal.
• Other severe, untreated or uncontrolled medical illness (e.g., severe heart failure or dementia).

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: XR-NTX; Xr-NTX 380mg IM injection monthly x 6 months	Drug: XR-NTX (Extended-Release Naltrexone); 380mg (4cc) XR-NTX administered by IM injection 1x/month for 6 months.; Other Names: Vivitrol
Active Comparator: Oral Naltrexone; Oral naltrexone 50mg/day x 6 months	Drug: Oral Naltrexone (O-NTX); 50mg pill form of naltrexone taken 1x/day for 6 months.; Other Names: Revia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Alcohol Abstinence or Moderate Drinking	Percentage of participants who had the following number of drinks (≤2 drinks/day, men; ≤1 drink/day, women; and ≤2 heavy drinking occasions/month) during the final 20 of 24 weeks of primary care-based Medical Management for alcohol dependence.	4-24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness	To estimate the incremental cost-effectiveness of XR-NTX vs. O-NTX, both in conjunction with primary care-based medical management. Economic data will be derived primarily from the Economic Form 90, Non-Study Medical Service and electronic medical records assessments, EQ-5D (functional status), and a cost survey or standardized question querying patient reports of specific non-medical related costs (including lost/gained work, lost/gained dependent care, transportation costs, arrests, motor vehicle accidents) collected at baseline and at week 10, 18, 26, and 48 assessments.	0-24 weeks
Patient-level Predictors of Effectiveness	To identify patient-level characteristics (gender, ethnicity, pre-treatment abstinence, voluntary specialty alcohol treatment and Alcoholics Anonymous involvement) associated with effectiveness in both arms. Baseline Demographic and Timeline Follow-Back and in-study Non-Study Medical Service questionnaires will characterized these patient-level variables.	4-24 weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Joshua D. Lee, MD, MSc, NYU School of Medicine, Dept. Population Health

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: July 8, 2013
• First Posted (Estimate): July 9, 2013

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: alcohol dependence; primary care; Naltrexone; Extended-release naltrexone; Medical Management; Vivitrol; XR-NTX; Oral naltrexone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 12-02263