Naltrexone vs Buprenorphine-Naloxone for Opioid Dependence in Norway

Study Overview
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Brief Summary
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Persons dependent on opioids like heroin, morphine, or codeine have a high risk of relapse, overdose and overdose death. This risk is elevated even further following discharge from treatment or correctional institutions where patients have been detoxified. At the moment, state-of-the-art treatment is based on maintaining the dependence on opioids by daily intake of opioid medications like methadone or buprenorphine. Recently, a medication containing the blocking agent naltrexone was approved in the US; this does not maintain dependence but instead blocks heroin and other opioids for 28 days after intramuscular administration. This study will conduct a 12-week randomized comparison of naltrexone intramuscular suspension (XL-NTX) with daily buprenorphine-naloxone in OMT. Medication will start preceding discharge from a treatment or correctional facility to participating catchment regions in Norway. The main hypotheses are that XL-NTX will do equally well as - or better than - OMT on the proportion of biological samples negative for opioids, retention, self-reported use of alcohol and illicit drugs. Following the 12-week randomized period, there will be a 36-week period where participants can receive the study medication of their choice. After the end of the study, data from national registry databases can be collected for a further 12 months on outcomes such as recidivism, mortality and morbidity.

Official Title
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Optimal Prevention of Overdose Deaths and Opioid Relapse Following Discharge: A Multi-Center RCT of Naltrexone Versus Buprenorphine in Norway

Conditions
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Opioid Dependence

Intervention / Treatment
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* Drug: Naltrexone intramuscular suspension
* Drug: Buprenorphine-naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Opioid dependence (DSM-IV TR) Age 18 or above Applied & Approved for Norway's national OMT program Discharge within 30 days of inclusion from a controlled environment; e.g. inpatient treatment or correctional (prison) facility Voluntarily seeking treatment for opioid dependence Exclusion Criteria: Pregnant or breast-feeding Acute or recurring severe psychiatric disorder, e.g. psychosis, suicidality Serious debilitation of liver or renal function (e.g. Child-Pugh level C) Use of excluded medication Known intolerance to study drugs or their ingredients Employment in firm manufacturing one of the study drugs or close relation to such person

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone intramuscular suspension<br>Extended release naltrexone injections 380mg | Drug: Naltrexone intramuscular suspension<br>* A standard dosage of 380 mg / month of naltrexone intramuscular suspension will be administered<br>* Other names: Vivitrol;|
| Active Comparator: Buprenorphine-naloxone<br>Flexible oral dose 4-24 mg daily | Drug: Buprenorphine-naloxone<br>* Buprenorphine-naloxone is administered daily and provided in accordance with existing guidelines for OMT in Norway (treatment-as-usual).<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of biological samples negative/positive for opioid agonists |  | Week 1-12 post discharge | 
| Retention |  | Week 1-12 post discharge | 
| Days of use or abstinence from opioids |  | Week 1-12 post discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use of other substances of abuse |  | Week 1-48 | 
| Mental health | Self-reported mental health | Week 1-12 or 1-48 | 
| Somatic health | Self-reported and/or assessed by study personnel | Week 1-12 or 1-48 post discharge | 
| Psychosocial problems | Psychosocial problems like recidivism, employment, family problems. Self-reported or registry-based. | Week 1-12, Week 1-48, & Wk 49-100 |