Extended-release Naltrexone and Care Management for Alcohol Dependent Frequent Emergency Department Users
Condition: Alcohol Dependence; Alcohol Use Disorder
MeSH terms: Emergencies; Alcoholism; Alcohol Drinking
Study type: Interventional
Phase: Phase 4

Summary: 
      Our primary aim is to assess the feasibility of initiating treatment in the ED with
      extended-release naltrexone (XR-NTX) plus care management (CM) vs. standard care and
      continuing care in cooperation with clinic providers as well as how best to assess outcomes.
      Secondarily, the investigators will explore its effect on various health outcomes (healthcare
      utilization and engagement, expenditures, drinking and consequences, quality of life) as well
      as the association of patient-level characteristics (e.g. sex, race, baseline drinking,
      health and psychosocial factors, mu opioid receptor genotype) with effectiveness. Determining
      both how to implement XR-NTX+CM and rigorously test its effects in the ED (phase 1) is
      essential before planning a large-scale effectiveness trial (phase 2).
    

Detailed description: 
      Aim #1: To conduct a feasibility and acceptability study of XR-NTX+CM treatment in alcohol
      dependent patients with frequent ED use.

      Hypothesis: Enrollment of a limited number of subjects will allow identification of optimal
      processes for a definitive trial.

      Aim #2: To conduct an analysis of the effect of this intervention on healthcare utilization
      and engagement, drinking outcomes, quality of life, and consequences of drinking (initial
      analysis will be exploratory).

      Hypothesis: Measuring changes in healthcare utilization, drinking metrics, and indicators of
      quality of life and consequences will provide preliminary data on intervention effect size on
      various outcomes of interest to inform the second phase, definitive trial.

      Aim #3: To identify patient-level characteristics associated with effectiveness.

      Hypothesis: Exploratory analysis of patient and system-level characteristics possibly
      associated with effectiveness will inform treatment choice to maximize the probability of
      successful outcome. Factors assessed will include data collected in ongoing investigations of
      pharmacotherapy for alcohol dependence, including mu opioid receptor (OPRM1) genotypes, to
      facilitate comparison across study populations and settings.

      This a phase IV, randomized, open-label, non-placebo-controlled, single-center study of the
      feasibility, acceptability, and effect of initiating treatment in the ED with
      extended-release naltrexone 380mg intramuscular injection compared to standard care in
      subjects with severe alcohol use disorders (i.e. alcohol dependence) and frequent emergency
      department use. In the first two years, we will finalize study preparations, recruit and
      randomize 50 subjects for the pilot phase of this study. The duration of each subject's
      participation will be 12 months. Thereafter, in the second phase of study, we will enroll an
      additional 250 subjects (for a total of 300 subjects) to address remaining feasibility and
      acceptability concerns and test effects.

      The study investigators (PI and RA) will collect process data, including barriers and
      facilitators encountered in the completion of all study procedures. For the following study
      procedures, study investigators (the PI and RAs) will enter data directly into New York
      University Langone Medical Center (NYULMC) internal REDCap system for use on portable tablet
      computers.

      Synopsis of Study Procedures:

      The following study procedures are described in greater detail elsewhere in this protocol.

      Patients will be prescreened for potential eligibility and added to an automated alert system
      linked to ED registration by Bellevue Care Managers as part of an ongoing quality improvement
      initiative. When a potentially eligible patient presents to the ED, an automated page will be
      delivered to the study PI and Bellevue ED social work and care management staff, prompting
      consultation and potential referral of the patient to study investigators (PI/RA) for
      recruitment (See 4.3 Subject Recruitment and Screening). ED medical providers (inclusive of
      ED physicians, nurses, social workers, and care managers) will notify study investigators
      (PI/RA) when potentially eligible patients are present in the ED. The medical provider will
      introduce the PI/RA to clinically sober and medically stable patients who have given their
      permission to be approached. The PI/RA will describe the study, confirm capacity to consent
      using the University of California San Diego Brief Assessment of Capacity to Consent to
      Research (UBACC), and obtain written informed consent. The PI/RA will confirm eligibility by
      performing a chart and laboratory review (liver enzymes, pregnancy, urine drug screen),
      history and examination, and diagnostic interview to confirm alcohol dependence and assess
      for opioid use and chronic pain. The PI/RA will conduct research intake assessments and
      interview and collect blood for biomarker (5mL) and genetic (10mL) analyses. The PI/RA will
      randomize subjects to intervention (XR-NTX+CM) or Standard Care using a random number
      generator with randomly permuted blocks with allocations contained within opaque sealed
      envelopes.

        1. For subjects randomized to the Intervention Arm, the PI/RA will confirm the drug screen
           is negative for opioids prior to administering XR-NTX 380mg as an intramuscular gluteal
           injection. The PI/RA will facilitate a person-centered, harm-reduction-based
           motivational interview, , and psychosocial assessment/interview to inform subjects'
           care-management plans. Subjects will receive a one-week referral to Bellevue ambulatory
           care for initial Alcohol-Medical Management (MM) and will also be scheduled every 4
           weeks (after most recent XR-NTX injection) for MM and XR-NTX injections. When possible,
           participants who miss MM-injection visits will be navigated to clinic upon their next ED
           presentation and/or may receive MM and XR-NTX in the ED. XR-NTX will be administered by
           the PI or a provider (physician, physician assistant, or registered nurse) who is
           trained in the administration of XR-NTX. The schedule for MM-Injection visits is weeks
           4, 8, 12, 16, 20, and 24. Participants may be offered to continue XR-NTX treatment
           through this study for as many has 12 injections in total as we explore the feasibility,
           acceptability and potential benefits of extending treatment duration to 12 months. The
           schedule for potential additional MM-Injection visits is weeks 28, 32, 36, 40, and 44.
           Research assessment visits will occur at weeks 12, 24, and 48 and may be conducted up to
           28 days prior to- or 90 days after- date in which research visits are due. During
           research visits, the PI/RA will repeat the assessments that were conducted at the
           initial enrollment visit plus adverse events and participant satisfaction and we will
           collect a 5mL blood sample to examine alcohol consumption biomarkers. Subject
           participation ends after the week-48 research visit.

        2. For subjects randomized to the Standard care arm, the PI/RA will provide referral to
           Bellevue ambulatory care for MM without further intervention. Research assessment visits
           will occur at weeks 12, 24, and 48 and may be conducted up to 28 days prior to- or 90
           days after- date in which research visits are due. During research visits, the PI/RA
           will repeat the assessments that were conducted at the initial enrollment visit plus
           adverse events and participant satisfaction and we will collect a 5mL blood sample to
           examine alcohol consumption biomarkers. Subject participation ends after the week-48
           research visit.
    

Intervention name(s): XR-NTX+CM (Extended-Release Naltrexone plus Care Management)
Intervention type(s): Drug
Intervention description(s): The intervention arm will receive extended-release naltrexone (XR-NTX) 380mg (4 mL) to be administered as an intramuscular gluteal injection every 28 days up to 12 doses total. Expedited referral to alcohol-medical management. Care Management will include coordination of health care and social services for at least 12 months. Harm-reduction counseling and motivational interviewing to identify and work towards goals. The Standard care arm will receive an expedited alcohol-medical management referral.
Other intervention name(s): Vivitrol
Intervention MeSH terms: Naltrexone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Alcohol Dependence; Alcohol Use Disorder; Care Management; Case Management; Emergency Care Services; Emergency Department; Emergency Room; Extended-release naltrexone; Frequent Users; Health Care Utilization; Medical Management; Naltrexone; Population Health; Public Health; Vivitrol; XR-NTX; XR-NTX+CM; Alcoholism; Alcohol-Related Disorders; Central Nervous System Agents; Chemically-Induced Disorders; Clinical Trial; Emergency Medicine; Mental Disorders; Narcotic Antagonists; Peripheral Nervous System Agents; Pharmacologic Actions; Physiological Effects of Drugs; Sensory System Agents; Substance-Related Disorders