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Trial record 1 of 1 for:    nct02032433
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Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02032433
First Posted: January 10, 2014
Last Update Posted: March 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institute on Drug Abuse (NIDA)
The EMMES Corporation
Information provided by (Responsible Party):
New York University School of Medicine
  Purpose

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.


Condition Intervention Phase
Opioid Use Disorder Drug: Extended-Release Naltrexone Drug: Buprenorphine-Naloxone Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CTN-0051: Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Time to relapse [ Time Frame: Days 21 - 195 ]
    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. The primary outcome measure will be the time to the event, with the event called relapse.


Secondary Outcome Measures:
  • Proportion successfully inducted onto assigned study medication (binary: did or did not receive first dose of XR-NTX, or achieve maintenance dose of BUP-NX) [ Time Frame: Days 0 - 156 ]

    Hypothesis: BUP-NX will produce higher rate of successful induction than XR-NTX

    Significance/Rationale: XR-NTX induction requires completion of detoxification, whereas BUP-NX induction only requires onset of withdrawal symptoms. Thus XR-NTX may have more dropouts after randomization but prior to XR-NTX induction.


  • Adverse Events related to study medications [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX and BUP-NX will produce equivalent rates of SAEs, and equivalent rates of AEs, though AE pattern will differ somewhat (e.g. injection site reactions with XR-NTX)

    Significance/Rationale: Careful documentation of SAEs and AEs, including overdose episodes, would be considered essential safety data, and important component of a comparative effectiveness trial.


  • Opioid abstinence over time while on study medication (Weekly TLFB, confirmed by urine drug screens) [ Time Frame: Days 0 - 195 ]

    Hypothesis: XR-NTX will produce greater opioid abstinence than BUP-NX

    Significance/Rationale: XR-NTX produces complete blockade of opioid effects, so that during treatment with monthly injections, opioid use can be expected to be minimal. In contrast BUP-NX may not produce complete blockade, or patients may reduce or stop doses for a few days and substitute other opioids (heroin, prescription opioids).


  • Alcohol and other drug use, over time (TLFB and UDS) [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX will be superior to BUP-NX in producing abstinence from alcohol and other drugs

    Significance/Rationale: Clinical trials show XR-NTX is effective for treatment of alcohol dependence, and naltrexone has some evidence of efficacy for stimulant dependence.


  • Cigarette smoking (FTND, Tobacco Use Questionnaire, VAS nicotine craving) [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX will reduce cigarette smoking compared to BUP-NX

    Significance/Rationale: Naltrexone has been studied as a treatment for nicotine dependence, with some support from clinical trials, although inconsistent. Given high morbidity and mortality associated with nicotine dependence, a comparative advantage of one or the other of these treatments at reducing smoking would be valuable to examine.


  • Opioid Craving (VAS) over time [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX will be superior to BUP-NX in reducing opioid craving

    Significance/Rationale: Krupitsky et al (Lancet 2011) pivotal XR-NTX trial showed, surprisingly, that XR-NTX reduced craving substantially compared to placebo.


  • Subacute withdrawal symptoms over time (HAM-D, SOWS) [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX will produce greater severity of subacute withdrawal symptoms than BUP-NX during the first month after randomization, but will be equivalent to BUP-NX in months 2 to 6

    Significance/Rationale: Low-grade withdrawal-like symptoms (dubbed "naltrexone flu" by the Columbia group, and consisting typically of insomnia, fatigue, and anorexia, though not drug craving) have been observed in some patients in the 1 to 4 weeks after naltrexone initiation, resolving gradually. Further characterization of this syndrome would be important for developing treatment guidelines.


  • Problems related to drug abuse (ASI-Lite and EQ-5D) [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX will be superior to BUP-NX

    Significance/Rationale: Greater opioid and non-opioid abstinence on XR-NTX will result in fewer problems associated with active drug abuse.


  • HIV risk behavior over time (RAB and other HIV risk measures) [ Time Frame: Days 0 - 279 ]

    Hypothesis: XR-NTX and BUP-NX will be equivalent

    Significance/Rationale: The opioid-dependent population is at high risk for HIV, both from injection drug use and from unsafe sexual practices. Effective treatment for the opioid dependence may reduce HIV risk behavior. Given the high morbidity and mortality associated with HIV, a comparative advantage of one or the other of these treatments would be valuable to examine.


  • Cognitive function (Trails Making Test Parts A and B, Stroop) [ Time Frame: Days 0 - 195 ]

    Hypothesis: XR-NTX and BUP-NX will be equivalent

    Significance/Rationale: Some providers and policy-makers are concerned that patients maintained on BUP-NX will have opioid-agonist-related cognitive impairment.


  • Economic costs [ Time Frame: Days 0 - 279 ]
    Estimate and compare the economic costs of opioid dependence treatment with XR-NTX and BUP-NX from the perspectives of the treatment provider, the payer, and the patient.

  • Quality-adjusted life year (QALY) outcomes [ Time Frame: Days 0 - 279 ]
    Estimate and compare quality-adjusted life year (QALY) outcomes for opioid dependence treatment with XR-NTX and BUP-NX.

  • Cost-effectiveness and cost-benefit [ Time Frame: Days 0 - 279 ]
    From a societal perspective, evaluate the incremental cost-effectiveness and cost-benefit of opioid dependence treatment with XR-NTX compared to BUP-NX.


Enrollment: 772
Actual Study Start Date: January 2014
Study Completion Date: January 25, 2017
Primary Completion Date: January 25, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Extended-Release Naltrexone
Extended-Release Naltrexone (Vivitrol)
Drug: Extended-Release Naltrexone
Extended-Release Naltrexone (Vivitrol®)
Other Name: Vivitrol®
Active Comparator: Buprenorphine-Naloxone
Buprenorphine-Naloxone (Suboxone)
Drug: Buprenorphine-Naloxone
Buprenorphine-Naloxone (Suboxone®)
Other Name: Suboxone®

Detailed Description:

For opioid-dependent patients in the U.S. and most of the rest of the world, detoxification or detoxification followed by short term residential treatment, with the goal of achieving long-term abstinence from opioid misuse is a mainstay of treatment. Nonetheless, the majority of patients treated in this way will relapse to opioid misuse, leading to a costly and ineffectual cycle of readmission for repeated detoxifications.

The overarching goal of CTN-0051 is to foster adoption of new relapse-prevention pharmacotherapies in community-based treatment programs (CTPs) where these could have a substantial public health impact. To this end 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 CTN-affiliated CTPs that provide or partner with detoxification services (inpatient/residential) which have the capacity to maintain participants opioid-free for approximately 3-7 days, have the capacity to provide medication-assisted therapy, and can provide a minimum of one group or individual counseling session per week during the 24-week treatment period. 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). To maximize generalizability, the point of randomization is flexible, from shortly after program admission until just prior to program discharge. A data analysis modification (assessment of whether the early vs. late randomizers have a differential treatment effect and if so, time to relapse will be estimated for early and late randomizers separately) will occur if differential treatment initiation is a problem for cases randomized prior to completing detoxification (i.e., significantly fewer early randomizers are able to complete detoxification and XR-NTX induction).

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. The primary outcome measure will be the time to the event, with the event called relapse. 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.

Toward the end of the 24-week treatment period, participants are referred for follow-up care in the community (which could include pharmacotherapy if desired and available), and follow-up outcomes are assessed at week 28 and week 36 after randomization. For participants receiving BUP-NX, who do not wish to continue, or for whom community resources are not available, the study provides a two-week BUP-NX taper.

In an ancillary genetics study we plan to study functional variants in three genes (OPRM1, OPRK1 and PDYN), known to affect the dynamic response to opioid receptor ligands. These variants will be evaluated in CTN-0051 for their contribution to treatment retention, abstinence, and depression. Blood collection for DNA extraction will occur at the same time that blood is collected for medical safety and liver function evaluation, precluding the need for an additional needle-stick. Coded blood samples for the genetics studies will be sent to the NIDA Center for Genetics Repository.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Male or female
  • 18 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

Exclusion Criteria

  • 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:

    1. 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;
    2. Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview;
    3. 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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02032433


Locations
United States, California
Tarzana Treatment Centers
Tarzana, California, United States, 91356
United States, Florida
Gateway Community Services, Inc.
Jacksonville, Florida, United States, 32201
United States, Maryland
Avery Road Treatment Center
Rockville, Maryland, United States, 20853
United States, Massachusetts
Stanley Street Treatment and Resources
Fall River, Massachusetts, United States, 02720
United States, New Mexico
Turquoise Lodge Hospital
Albuquerque, New Mexico, United States, 87108
United States, New York
Bellevue Hospital Center
New York, New York, United States, 10016
United States, Ohio
Maryhaven
Columbus, Ohio, United States, 43207
United States, Washington
Evergreen Treatment Services
Seattle, Washington, United States, 98134
Sponsors and Collaborators
New York University School of Medicine
National Institute on Drug Abuse (NIDA)
The EMMES Corporation
Investigators
Principal Investigator: John Rotrosen, MD New York University School of Medicine
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT02032433     History of Changes
Other Study ID Numbers: 12-03133
2 UG1 DA0113035-14 ( Other Grant/Funding Number: NIDA )
First Submitted: December 30, 2013
First Posted: January 10, 2014
Last Update Posted: March 24, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by New York University School of Medicine:
extended-release naltrexone (Vivitrol)
buprenorphine-naloxone (Suboxone)
comparative effective
relapse prevention

Additional relevant MeSH terms:
Buprenorphine
Buprenorphine, Naloxone Drug Combination
Naltrexone
Naloxone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists