Clinical trial NCT01717963: Naltrexone vs Buprenorphine-Naloxone for Opioid Dependence in Norway
Official title: Optimal Prevention of Overdose Deaths and Opioid Relapse Following Discharge: A Multi-Center RCT of Naltrexone Versus Buprenorphine in Norway
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid Dependence
Lead sponsor: University of Oslo
Sponsor class: OTHER
Collaborators: name: The Research Council of Norway
name: The Royal Norwegian Ministry of Health
name: Norwegian Institute of Public Health
name: Oslo University Hospital
name: University Hospital, Akershus
name: Haukeland University Hospital
name: Helse Stavanger HF
name: The Hospital of Vestfold
name: Ostfold Hospital Trust
First posted: 2012-10-31
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of biological samples negative/positive for opioid agonists
timeFrame: Week 1-12 post discharge
measure: Retention
timeFrame: Week 1-12 post discharge
measure: Days of use or abstinence from opioids
timeFrame: Week 1-12 post discharge
Secondary outcomes:
measure: Use of other substances of abuse
timeFrame: Week 1-48
measure: Mental health
timeFrame: Week 1-12 or 1-48
measure: Somatic health
timeFrame: Week 1-12 or 1-48 post discharge
measure: Psychosocial problems
timeFrame: Week 1-12, Week 1-48, & Wk 49-100
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Akershus University Hospital
state: Akershus
city: Bergen
country: Norway
facility: Haukeland University Hospital
state: Hordaland
city: Stavanger
country: Norway
facility: Stavanger University Hospital
state: Rogaland
city: Tonsberg
country: Norway
facility: Vestfold Hospital Trust
state: Vestfold
city: Oslo
country: Norway
facility: Oslo University Hospital, Avdeling for Rus og Avhengighet
Study officials:
affiliation: University of Oslo
name: Lars Tanum, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Opheim A, Gaulen Z, Solli KK, Latif ZE, Fadnes LT, Benth JS, Kunoe N, Tanum L. Risk of Relapse Among Opioid-Dependent Patients Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone: A Randomized Clinical Trial. Am J Addict. 2021 Sep;30(5):453-460. doi: 10.1111/ajad.13151.
citation: Latif ZE, Solli KK, Opheim A, Kunoe N, Benth JS, Krajci P, Sharma-Haase K, Tanum L. No increased pain among opioid-dependent individuals treated with extended-release naltrexone or buprenorphine-naloxone: A 3-month randomized study and 9-month open-treatment follow-up study. Am J Addict. 2019 Feb;28(2):77-85. doi: 10.1111/ajad.12859. Epub 2019 Jan 31.
citation: Latif ZE, Saltyte Benth J, Solli KK, Opheim A, Kunoe N, Krajci P, Sharma-Haase K, Tanum L. Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With Extended-Release Naltrexone vs Buprenorphine-Naloxone: A Randomized Clinical Trial and Follow-up Study. JAMA Psychiatry. 2019 Feb 1;76(2):127-134. doi: 10.1001/jamapsychiatry.2018.3537.
citation: Solli KK, Latif ZE, Opheim A, Krajci P, Sharma-Haase K, Benth JS, Tanum L, Kunoe N. Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial. Addiction. 2018 Oct;113(10):1840-1849. doi: 10.1111/add.14278. Epub 2018 Jun 22.
citation: Tanum L, Solli KK, Latif ZE, Benth JS, Opheim A, Sharma-Haase K, Krajci P, Kunoe N. Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial. JAMA Psychiatry. 2017 Dec 1;74(12):1197-1205. doi: 10.1001/jamapsychiatry.2017.3206.
citation: Kunoe N, Opheim A, Solli KK, Gaulen Z, Sharma-Haase K, Latif ZE, Tanum L. Design of a randomized controlled trial of extended-release naltrexone versus daily buprenorphine-naloxone for opioid dependence in Norway (NTX-SBX). BMC Pharmacol Toxicol. 2016 Apr 28;17(1):18. doi: 10.1186/s40360-016-0061-1.