NCT02032433

Brief Summary

CTN-0051 assesses the comparative effectiveness of extended release injectable naltrexone (XR-NTX, Vivitrol®), an opioid antagonist recently approved and indicated for the prevention of relapse to opioid dependence, versus buprenorphine-naloxone (BUP-NX, Suboxone®), a high affinity partial agonist indicated for maintenance treatment of opioid dependence, as pharmacotherapeutic aids to recovery. The study is conducted in 8 NIDA Clinical Trials Network affiliated community based treatment programs. Up to 600 eligible participants will be randomized to treatment with XR-NTX or BUP-NX for 24 weeks (sufficient to include 350 participants who are randomized more than 72 hours after their last opioid). The primary goal of the study is to estimate the difference, if one exists, between XR-NTX and BUP-NX in the distribution of the time to relapse (i.e.., loss of persistent abstinence) during the 6-month trial. Secondary objectives are to: (1) compare outcome on XR-NTX versus BUP-NX across a range of clinical safety and secondary efficacy domains, and (2) explore demographic and, clinical, and genetic predictors of successful treatment and moderators of differential effectiveness (i.e., what variables may help clinicians choose which of these treatments is best for a given patient).), and (3) collect a limited dataset to permit analyses of economic costs and benefits of the two treatments.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
570

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jan 2014

Typical duration for phase_4

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 30, 2013

Completed
11 days until next milestone

First Posted

Study publicly available on registry

January 10, 2014

Completed
19 days until next milestone

Study Start

First participant enrolled

January 29, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 25, 2017

Completed
6 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2017

Completed
12 months until next milestone

Results Posted

Study results publicly available

January 19, 2018

Completed
Last Updated

August 13, 2020

Status Verified

July 1, 2020

Enrollment Period

3 years

First QC Date

December 30, 2013

Results QC Date

November 24, 2017

Last Update Submit

July 30, 2020

Conditions

Keywords

extended-release naltrexone (Vivitrol)buprenorphine-naloxone (Suboxone)comparative effectiverelapse prevention

Outcome Measures

Primary Outcomes (2)

  • Time to Relapse (Intent to Treat Population)

    Relapse occurs if the participant is using any non-protocol prescribed opioids regularly starting at day 21 post-randomization or thereafter. Operationally, relapse is defined as either: (a) four consecutive opioid use weeks, or (b) seven consecutive days of use by self-report. A use week is defined as any week during which a participant self-reports at least one day of use during that week, provides a urine sample positive for non-protocol opioids, or fails to provide a urine sample. Self-report of opioid (heroin or prescription opioids) and other substance use is ascertained at each weekly study visit using the Timeline Follow-Back for each day leading back to the previous visit. Urine is collected at each study visit and tested for opioids. A missed UDS counts as a use week.

    Weeks 3-24

  • Time to Relapse (Per Protocol Population)

    Relapse occurs if the participant is using any non-protocol prescribed opioids regularly starting at day 21 post-randomization or thereafter. Operationally, relapse is defined as either: (a) four consecutive opioid use weeks, or (b) seven consecutive days of use by self-report. A use week is defined as any week during which a participant self-reports at least one day of use during that week, provides a urine sample positive for non-protocol opioids, or fails to provide a urine sample. Self-report of opioid (heroin or prescription opioids) and other substance use is ascertained at each weekly study visit using the Timeline Follow-Back for each day leading back to the previous visit. Urine is collected at each study visit and tested for opioids. A missed UDS counts as a use week.

    Weeks 3-24

Secondary Outcomes (56)

  • Number Successfully Inducted Onto Assigned Study Medication

    Weeks 0-24

  • Adverse Events Related to Study Medications

    Weeks 0-36

  • Opioid Abstinence Over Time While on Study Medication (Subjective)

    Weeks 0-24

  • Alcohol Use Over Time, Drinks Per Day, Past 30 Days, W0

    Week 0

  • Cigarette Smoking, W0, 10 or Less

    Week 0

  • +51 more secondary outcomes

Study Arms (2)

Extended-Release Naltrexone

ACTIVE COMPARATOR

Extended-Release Naltrexone (Vivitrol)

Drug: Extended-Release Naltrexone

Buprenorphine-Naloxone

ACTIVE COMPARATOR

Buprenorphine-Naloxone (Suboxone)

Drug: Buprenorphine-Naloxone

Interventions

Extended-Release Naltrexone (Vivitrol®)

Also known as: Vivitrol®
Extended-Release Naltrexone

Buprenorphine-Naloxone (Suboxone®)

Also known as: Suboxone®
Buprenorphine-Naloxone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female
  • years of age and older
  • Meet DSM-5 criteria for opioid-use disorder (heroin and/or prescription opioids)
  • Have used opioids other than as specifically prescribed within thirty days prior to consent
  • Seeking treatment for opioid dependence and willing to accept "agonist-based" or "antagonist-based" therapy
  • In good-enough general health, as determined by the study physician on the basis of medical history, review of systems, physical exam and laboratory assessments, to permit treatment with XR-NTX or BUP-NX
  • Able to provide written informed consent
  • Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study
  • If female of childbearing potential, be willing to practice an effective method of birth control for the duration of participation in the study

You may not qualify if:

  • Serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make study participation hazardous to the participant, or compromise study findings or would prevent the participant from completing the study. Examples include:
  • Disabling or terminal medical illness (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease) as assessed by medical history, review of systems, physical exam and/or laboratory assessments;
  • Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview;
  • Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use likely to require a complicated medical detoxification (routine alcohol and sedative detoxifications may be included)
  • LFTs (ALT, AST) greater than 5 times upper limit of normal
  • Suicidal or homicidal ideation that requires immediate attention
  • Known allergy or sensitivity to buprenorphine, naloxone, naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or other components of the Vivitrol® diluent
  • Maintenance on methadone at doses of 30mg or greater at the time of signing consent
  • Presence of pain of sufficient severity as to require ongoing pain management with opioids
  • Pending legal action or other reasons that might prevent an individual from completing the study
  • If female, currently pregnant or breastfeeding, or planning on conception
  • Body habitus that, in the judgment of the study physician, precludes safe intramuscular injection of XR-NTX (e.g., BMI\>40, excess fat tissue over the buttocks, emaciation)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Tarzana Treatment Centers

Tarzana, California, 91356, United States

Location

Gateway Community Services, Inc.

Jacksonville, Florida, 32201, United States

Location

Avery Road Treatment Center

Rockville, Maryland, 20853, United States

Location

Stanley Street Treatment and Resources

Fall River, Massachusetts, 02720, United States

Location

Turquoise Lodge Hospital

Albuquerque, New Mexico, 87108, United States

Location

Bellevue Hospital Center

New York, New York, 10016, United States

Location

Maryhaven

Columbus, Ohio, 43207, United States

Location

Evergreen Treatment Services

Seattle, Washington, 98134, United States

Location

Related Publications (13)

  • Kornor H, Lobmaier PPK, Kunoe N. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2025 May 9;5(5):CD006140. doi: 10.1002/14651858.CD006140.pub3.

  • Brandt L, Odom GJ, Hu MC, Castro C, Balise RR; CTN-0094 Team. Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions. Addiction. 2024 Jul;119(7):1289-1300. doi: 10.1111/add.16494. Epub 2024 Apr 14.

  • Foot C, Korthuis PT, Tsui JI, Luo SX, Chan B, Cook RR. Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder. Addiction. 2024 Jan;119(1):149-157. doi: 10.1111/add.16334. Epub 2023 Sep 15.

  • Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database Syst Rev. 2022 Sep 5;9(9):CD011117. doi: 10.1002/14651858.CD011117.pub3.

  • Tsui JI, Campbell ANC, Pavlicova M, Choo TH, Lee JD, Cook RR, Shulman M, Nunes EV, Rotrosen J. Methamphetamine/amphetamine use over time among persons with opioid use disorders treated with buprenorphine/naloxone versus extended-release naltrexone. Drug Alcohol Depend. 2022 Jul 1;236:109469. doi: 10.1016/j.drugalcdep.2022.109469. Epub 2022 Apr 21.

  • Jelovac A, McLoughlin DM. Twelve-Month Outcomes for Remitters Following Electroconvulsive Therapy for Depression. J Clin Psychiatry. 2022 Apr 18;83(3):21lr14371. doi: 10.4088/JCP.21lr14371. No abstract available.

  • Na PJ, Scodes J, Fishman M, Rotrosen J, Nunes EV. Co-occurring Depression and Suicidal Ideation in Opioid Use Disorder: Prevalence and Response During Treatment With Buprenorphine-Naloxone and Injection Naltrexone. J Clin Psychiatry. 2022 Apr 18;83(3):21m14140. doi: 10.4088/JCP.21m14140.

  • Rudolph KE, Shulman M, Fishman M, Diaz I, Rotrosen J, Nunes EV. Association between dynamic dose increases of buprenorphine for treatment of opioid use disorder and risk of relapse. Addiction. 2022 Mar;117(3):637-645. doi: 10.1111/add.15654. Epub 2021 Oct 1.

  • Nunes EV Jr, Scodes JM, Pavlicova M, Lee JD, Novo P, Campbell ANC, Rotrosen J. Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment. Am J Psychiatry. 2021 Jul;178(7):660-671. doi: 10.1176/appi.ajp.2020.20060816. Epub 2021 Jun 25.

  • Fishman M, Wenzel K, Scodes J, Pavlicova M, Campbell ANC, Rotrosen J, Nunes E. Examination of Correlates of OUD Outcomes in Young Adults: Secondary Analysis From the XBOT Trial. Am J Addict. 2021 Sep;30(5):433-444. doi: 10.1111/ajad.13176. Epub 2021 Jun 1.

  • Shulman M, Choo TH, Scodes J, Pavlicova M, Wai J, Haenlein P, Tofighi B, Campbell ANC, Lee JD, Rotrosen J, Nunes EV. Association between methadone or buprenorphine use during medically supervised opioid withdrawal and extended-release injectable naltrexone induction failure. J Subst Abuse Treat. 2021 May;124:108292. doi: 10.1016/j.jsat.2021.108292. Epub 2021 Jan 16.

  • Lee JD, Nunes EV Jr, Novo P, Bachrach K, Bailey GL, Bhatt S, Farkas S, Fishman M, Gauthier P, Hodgkins CC, King J, Lindblad R, Liu D, Matthews AG, May J, Peavy KM, Ross S, Salazar D, Schkolnik P, Shmueli-Blumberg D, Stablein D, Subramaniam G, Rotrosen J. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018 Jan 27;391(10118):309-318. doi: 10.1016/S0140-6736(17)32812-X. Epub 2017 Nov 14.

  • Lee JD, Nunes EV, Mpa PN, Bailey GL, Brigham GS, Cohen AJ, Fishman M, Ling W, Lindblad R, Shmueli-Blumberg D, Stablein D, May J, Salazar D, Liu D, Rotrosen J. NIDA Clinical Trials Network CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT): Study design and rationale. Contemp Clin Trials. 2016 Sep;50:253-64. doi: 10.1016/j.cct.2016.08.004. Epub 2016 Aug 10.

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

vivitrolBuprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

BuprenorphineMorphinansOpiate AlkaloidsAlkaloidsHeterocyclic CompoundsNaloxoneHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Results Point of Contact

Title
John Rotrosen
Organization
NYU School of Medicine

Study Officials

  • John Rotrosen, MD

    NYU Langone Health

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 30, 2013

First Posted

January 10, 2014

Study Start

January 29, 2014

Primary Completion

January 25, 2017

Study Completion

January 31, 2017

Last Updated

August 13, 2020

Results First Posted

January 19, 2018

Record last verified: 2020-07

Data Sharing

IPD Sharing
Will not share

Data from this study will be available to researchers on the website, http://datashare.nida.nih.gov/ after the study is complete and the data analyzed. This website will not include information that can identify individual study participants.

Locations