Project OOPEN: Opioid Overdose Prevention, Education and Intervention

Study Overview
=================
Brief Summary
-----------------
This prospective, randomized emergency department trial will study the effectiveness of an intervention that combines opioid overdose prevention, education and intervention that includes take home naloxone with brief behavioral change counseling. The study will recruit both heroin users (n=500) and pharmaceutical opioid users at elevated risk for overdose (n=500). Outcomes of interest include subsequent opioid overdoses and overdose risk behaviors. Primary Aims The primary aims are to test whether those who receive the intervention compared to standard care have: 1) Lower rates of opioid non-fatal and fatal overdose; 2) Reduce drug use, inappropriate medication use, and other overdose risk behaviors. Secondary Aims The secondary aims are to test whether those who receive the intervention compared to standard care have: 3) More appropriate health care utilization (e.g. fewer emergency department visits and admissions to inpatient care); 4) Lower total health care costs; 5) Determine the prevalence of HIV risk behaviors among heroin and pharmaceutical opioid users at risk for overdose and whether the intervention impacts these behaviors.

Detailed Description
-----------------
Fatal overdoses involving pharmaceutical opioids have increased dramatically over the past decade, surpassing those related to heroin, and are the leading cause of drug overdose in much of the U.S. In Seattle-King County, 75% of drug overdoses involved pharmaceutical opioids and/or heroin in 2009. Opioid overdoses, heroin and pharmaceutical, are preventable and reversible. Research indicates that drug users and their partners can be successfully trained to recognize and reverse overdoses with naloxone (an opioid antagonist medicine or antidote). Despite active heroin overdose prevention, education and intervention programs with naloxone (OOPEN) in 15 states with thousands of overdose reversals and no serious adverse events, rigorous studies of these programs on rates of subsequent heroin overdoses have not been conducted. No OOPEN programs or studies have yet been implemented for pharmaceutical opioid users at elevated risk for overdose. The Emergency Department (ED) setting holds great promise for identifying and recruiting those at elevated risk of both heroin and pharmaceutical opioid overdose: 1) the ED study site for this proposal provides most services to those needing care for acute opioid related medical problems in Seattle, and 2) patients' need for urgent medical attention may heighten their concern about potential harms from opioids. Unique to this setting is the potential to identify high risk pharmaceutical opioid users, a population that is difficult to locate and engage. ED interventions using brief behavior change counseling (BBCC) have been shown to significantly improve health behaviors such as alcohol use and injury, to increase entry into drug treatment as well as to reduce costs. Evidence is promising, but limited, regarding the impact of BBCC on opioid related risk behaviors. This prospective, randomized ED trial will study the effectiveness of an intervention that combines OOPEN with BBCC for both heroin users (n=500) and pharmaceutical opioid users at elevated risk for overdose (n=500). The primary outcome is subsequent opioid overdoses, ascertained by follow up interviews conducted at 3, 6 and 12 months as well as via administrative records for up to 24 months (i.e. medical records, ambulance responses, and death certificates). Primary Aims The primary aims are to test whether those who receive the intervention compared to standard care have: 1) Lower rates of opioid non-fatal and fatal overdose; 2) Reduce drug use, inappropriate medication use, and other overdose risk behaviors. Secondary Aims The secondary aims are to test whether those who receive the intervention compared to standard care have: 3) More appropriate health care utilization (e.g. fewer emergency department visits and admissions to inpatient care); 4) Lower total health care costs; 5) Determine the prevalence of HIV risk behaviors among heroin and pharmaceutical opioid users at risk for overdose and whether the intervention impacts these behaviors.

Official Title
-----------------
A Trial to Prevent Opioid Overdose: E.D. Based Intervention & Take-home Naloxone

Conditions
-----------------
Opioid Overdose

Intervention / Treatment
-----------------
* Drug: OOPEN+BBCC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meets study definition of elevated risk of future opioid overdose Reason for visit is opioid overdose (regardless of frequency of use), or Use of pharmaceutical opioids not prescribed to the patient 2 or more times in the prior month, or Use of other opioids, alcohol, benzodiazepines or stimulants within two hours of using opioids 2 or more times in the prior month, or Average daily dose of prescribed opioids consumed is greater than10 mg morphine equivalent analgesic dose or higher for 15 or more days in the last 30. Enrolled in opioid substitution program (e.g. methadone or suboxone) and receiving doses. Use of heroin through any route of administration at least 2 times in the last 30 days (or if institutionalized recently, in the most recent month they were not institutionalized) with or without other risks being present. Use of pharmaceutical opioids at least 2 times in the last 30 days (or if institutionalized recently, in the most recent month they were not institutionalized) with other risks being present. Average daily dose of prescribed opioids consumed is 30 mg morphine equivalent analgesic dose or higher without other risks being present.(For adult medicine clinic patients only.) Exclusion Criteria: Unwilling to allow further access to medical or drug treatment records. Inability to communicate in English. Current active suicidal ideation. Significant cognitive or psychiatric impairment (per judgment of clinical staff) Inability to provide adequate contact information to assist with follow-up. Under age 18 or over age 70 at time of recruitment. Not currently living in Washington State or planning to move from Washington State within the following year. Receiving treatment for sexual assault. Have non-expired take-home naloxone at home, on their person, or in their possessions.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention (OOPEN+BBCC)<br>Study intervention, overdose prevention, education, intervention, brief behavioral change counseling, take-home naloxone, referral to local available resources. | Drug: OOPEN+BBCC<br>* Take-home naloxone is offered as part of a behavioral prevention intervention to reduce the occurrence of future opioid overdose.<br>|
| No Intervention: Control<br>Standard of care, referral to local available resources. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Fatal Opioid Overdose | Rate of fatal opioid overdose | One year | 
| Rate of Non-fatal Opioid Overdose | Rate of non-fatal opioid overdose | One year | 
| Elapsed Time Until Opioid Overdose | Elapsed time until opioid overdose | Up to1064 days | 
| Change in Overdose Risk (Change in Opioid Use - Heroin) | Determine whether changes in behavior occur that increase or decrease risk of future overdose. Behaviors being measured include the amount of opioids taken, the use of opioids alone, use of opioids with alcohol or other drugs or medications, possessing naloxone, use of opioids in an environment that supports continued opioid use.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Change in Overdose Risk (Change in Opioid Use - Prescription-Type Opioids) | Determine whether changes in behavior occur that increase or decrease risk of future overdose. Behaviors being measured include the amount of opioids taken, the use of opioids alone, use of opioids with alcohol or other drugs or medications, possessing naloxone, use of opioids in an environment that supports continued opioid use.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Change in Overdose Risk (Using Alone When Taking Opioids) | Determine whether changes in behavior occur that increase or decrease risk of future overdose. Behaviors being measured include the amount of opioids taken, the use of opioids alone, use of opioids with alcohol or other drugs or medications, possessing naloxone, use of opioids in an environment that supports continued opioid use. (Data table includes means at 3 month follow-up.) | 3 months | 
| Change in Overdose Risk (Use of Sedatives When Taking Opioids) | Determine whether changes in behavior occur that increase or decrease risk of future overdose. Behaviors being measured include the amount of opioids taken, the use of opioids alone, use of opioids with alcohol or other drugs or medications, possessing naloxone, use of opioids in an environment that supports continued opioid use. (Data table includes proportions at 3 month follow-up.) | 3 months | 
| Change in Overdose Risk (Use of Alcohol When Taking Opioids) | Determine whether changes in behavior occur that increase or decrease risk of future overdose. Behaviors being measured include the amount of opioids taken, the use of opioids alone, use of opioids with alcohol or other drugs or medications, possessing naloxone, use of opioids in an environment that supports continued opioid use.(Data table includes proportions at 3 month follow-up.) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Care Utilization (ED and Inpatient Admissions) | Appropriate health care utilization (e.g. fewer emergency department visits and admissions to inpatient care) | One year (annual rate) | 
| Change in HIV Risk Behaviors (Condom Use) | Determine whether change occurs in the number of sexual risk behaviors (such as engaging in intercourse without a condom) and/or injection use behaviors (such as sharing syringes) that may increase the risk of contracting HIV.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Change in HIV Risk Behaviors (Shared Syringes) | Determine whether change occurs in the number of sexual risk behaviors (such as engaging in intercourse without a condom) and/or injection use behaviors (such as sharing syringes) that may increase the risk of contracting HIV. (Data table includes proportions at 3 month follow-up.) | 3 months | 
| Change in Overdose Risk Behaviors and Perceptions (Take Home Naloxone) | Change in overdose response including naloxone availability and change in overdose risk perceptions. (Data table includes proportions at 3 month follow-up.) | 3 Months | 
| Change in Overdose Risk Behaviors and Perceptions (Likelihood of Overdose) | Change in overdose response including naloxone availability and change in overdose risk perceptions. (Data table includes proportions at 3 month follow-up.) | 3 Months | 
| Change in Overdose Risk Behaviors and Perceptions (Concerned About Overdose) | Change in overdose response including naloxone availability and change in overdose risk perceptions. (Data table includes proportions at 3 month follow-up.) | 3 Months | 
| Subgroup Analyses - Change in HIV Risk Behaviors (Condom Use) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Subgroup Analyses - Change in HIV Risk Behaviors (Shared Syringes) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Sub-group Analyses - Change in Overdose Risk (Change in Opioid Use - Heroin) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Sub-group Analyses - Change in Overdose Risk (Change in Opioid Use - Prescription Type Opioids) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Sub-group Analyses - Change in Overdose Risk (Using Alone When Taking Opioids) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes means at 3 month follow-up.) | 3 months | 
| Subgroup Analyses- Change in Overdose Risk (Use of Sedatives When Taking Opioids) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Subgroup Analyses- Change in Overdose Risk (Use of Alcohol When Taking Opioids) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 months | 
| Sub-group Analyses - Change in Overdose Risk Behaviors and Perceptions (Take Home Naloxone) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 Months | 
| Sub-group Analyses- Change in Overdose Risk Behaviors and Perceptions (Likelihood of Overdose) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 Months | 
| Sub-group Analyses- Change in Overdose Risk Behaviors and Perceptions (Concerned About Overdose) | Sub-group analyses- primary and secondary outcomes will be examined by homelessness status at baseline.(Data table includes proportions at 3 month follow-up.) | 3 Months | 
| Health Care Costs | Total health care costs | Two years | 
| Health Care Utilization | Rate and elapsed time until initiation of buprenorphine or methadone maintenance. (for those not on treatment medications) | Two years | 
| Health Care Utilization | Retention time on buprenorphine or methadone (for those on medications at baseline) | Two years | 
| Opioid Overdose - Crossover Analysis | Crossover analysis- Comparison group participants who obtain naloxone during the follow up period will be analyzed with those in the intervention arm and compared with those who did not obtain naloxone in the comparison arm to examine differences in overdose rates and elapsed time to overdose. | Two years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Elevated risk, opioid overdose