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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
570
Extended-Release Naltrexone (Vivitrol®)
Buprenorphine-Naloxone (Suboxone®)
Tarzana Treatment Centers
Tarzana, California, United States
Gateway Community Services, Inc.
Jacksonville, Florida, United States
Avery Road Treatment Center
Rockville, Maryland, United States
Stanley Street Treatment and Resources
Fall River, Massachusetts, United States
Turquoise Lodge Hospital
Albuquerque, New Mexico, United States
Bellevue Hospital Center
New York, New York, United States
Maryhaven
Columbus, Ohio, United States
Evergreen Treatment Services
Seattle, Washington, United States
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.
Time frame: 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.
Time frame: Weeks 3-24
Number Successfully Inducted Onto Assigned Study Medication
Binary Y/N assessment of whether the participant was or was not able to initiate their assigned study medication.
Time frame: Weeks 0-24
Adverse Events Related to Study Medications
Adverse events reported by participants and assessed by clinical staff for relatedness to study medication. These determinations were reviewed by the study medical monitor.
Time frame: Weeks 0-36
Opioid Abstinence Over Time While on Study Medication (Subjective)
Self report of opioid use by participants using the TLFB. At each visit, the TLFB was completed for dates going back to the last participant encounter.
Time frame: Weeks 0-24
Alcohol Use Over Time, Drinks Per Day, Past 30 Days, W0
Alcohol use over time, drinks per day, past 30 days, at week 0
Time frame: Week 0
Cigarette Smoking, W0, 10 or Less
Participants average cigarettes/day, in past 4 weeks, at week 0, equals 10 or less.
Time frame: Week 0
Opioid Craving Over Time W0
Opioid craving over time via VAS at week 0
Time frame: Week 0
Score of Subacute Withdrawal Symptoms Subscale Within Hamilton Depression (HAM-D) Rating Scale
The Subacute Withdrawal Symptoms Subscale consists of 6 symptoms. Classification of symptoms can be scored as: 0 - absent, 1 - doubtful or trivial, 2 - present. The total range of scores is 0 - 12, and the higher the total score the more severe the depression.
Time frame: Week 0
Score of Alcohol Subscale Within Addiction Severity Index (ASI) Scale
The Alcohol Subscale within ASI is one question that asks how bothered one has been by alcohol problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 0
Score of Sexual Behavior Subscale Within HIV Risk-Taking Behavior Scale (HRBS)
The Sexual Behavior Subscale consists of 5 questions. Each question is scored from 0-5, for a total score range of 0-25. Higher scores indicate a greater degree of risk-taking behavior.
Time frame: Week 0
Score on Trail Making Test Part A
Trail Making Test Part A consists of 25 circles distributed over a sheet of paper. The circles are number 1-25, and the patient is asked to draw lines to connect the numbers in ascending order. The patient is instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Higher scores reveal greater impairment.
Time frame: Week 0
Opioid Abstinence Over Time While on Study Medication (Objective)
A urine sample was obtained and tested for opioids at each in person visit; screening, prior to induction onto study medication, weekly through week 24 and at each of the follow up visits.
Time frame: Weeks 0-24
Cigarette Smoking, W0 0
Participants average cigarettes/day, in past 4 weeks, at week 0, equals none
Time frame: Week 0
Cigarette Smoking, W0 11-20
Participants average cigarettes/day, in past 4 weeks, at week 0, equals 11-20.
Time frame: Week 0
Cigarette Smoking, W0 21-30
Participants average cigarettes/day, in past 4 weeks, at week 0, equals 21-30
Time frame: Week 0
Cigarette Smoking, W0 31 or More
Participants average cigarettes/day, in past 4 weeks, at week 0, equals 31 or more
Time frame: Week 0
Cigarette Smoking, W24 0
Participants average cigarettes/day, in past 4 weeks, at week 24, equals none
Time frame: Week 24
Cigarette Smoking
Participants average cigarettes/day, in past 4 weeks, at week 24, equals 10 or less.
Time frame: Week 24
Cigarette Smoking, W24 11-20
Participants average cigarettes/day, in past 4 weeks, at week 24, equals 11-20.
Time frame: Week 24
Cigarette Smoking, W24 21-30
Participants average cigarettes/day, in past 4 weeks, at week 24, equals 21-30
Time frame: Week 24
Cigarette Smoking, W24 31 or More
Participants average cigarettes/day, in past 4 weeks, at week 24, equals 31 or more
Time frame: Week 24
Score on Opioid Craving Scale (OCS)
OCS is a brief 3-item measure used to measure opioid craving. The scale consists of 3 items rated on a visual analogue scale (VAS) from 1-10. The total range of score is 0-30, and a higher score indicates a stronger craver / desire to use opiates.
Time frame: Week 24
Score of Subacute Withdrawal Symptoms Subscale Within Hamilton Depression (HAM-D) Rating Scale
The Subacute Withdrawal Symptoms Subscale consists of 6 symptoms. Classification of symptoms can be scored as: 0 - absent, 1 - doubtful or trivial, 2 - present. The total range of scores is 0 - 12, and the higher the total score the more severe the depression.
Time frame: Week 24
Score on Subjective Opiate Withdrawal Scale (SOWS)
The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). The total range of scores is 0-64; the higher the score, the more intense the withdrawal.
Time frame: Week 0
Score on Subjective Opiate Withdrawal Scale (SOWS)
The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). The total range of scores is 0-64; the higher the score, the more intense the withdrawal.
Time frame: Week 24
Score of Sexual Behavior Subscale Within HIV Risk-Taking Behavior Scale (HRBS)
The Sexual Behavior Subscale consists of 5 questions. Each question is scored from 0-5, for a total score range of 0-25. Higher scores indicate a greater degree of risk-taking behavior.
Time frame: Week 24
Score of Condom Use Subscale Within HIV Risk-Taking Behavior Scale (HRBS)
The Sexual Behavior Subscale consists of 3 questions. Each question is scored from 0-5, for a total score range of 0-15. Higher scores indicate a greater degree of risk-taking behavior.
Time frame: Week 0
Score of Condom Use Subscale Within HIV Risk-Taking Behavior Scale (HRBS)
The Sexual Behavior Subscale consists of 3 questions. Each question is scored from 0-5, for a total score range of 0-15. Higher scores indicate a greater degree of risk-taking behavior.
Time frame: Week 24
Score on Trail Making Test Part A
Trail Making Test Part A consists of 25 circles distributed over a sheet of paper. The circles are number 1-25, and the patient is asked to draw lines to connect the numbers in ascending order. The patient is instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Higher scores reveal greater impairment.
Time frame: Week 24
Score on Trail Making Test Part B
Part B consists of 25 circles distributed over a sheet of paper. In Part B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern, by alternating between the numbers and letters. Results are reported as the number of seconds required to complete the task.
Time frame: Week 0
Score on Trail Making Test Part B
Part B consists of 25 circles distributed over a sheet of paper. In Part B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern, by alternating between the numbers and letters. Results are reported as the number of seconds required to complete the task.
Time frame: Week 24
Score on Word Card of Stoop Test
The "word card" of the Stoop Test has the names of colors printed in black and white (100 items to be named). The patient's basic score is the total time he/she takes to utter the 100 words on the card.
Time frame: Week 0
Score on Word Card of Stoop Test
The "word card" of the Stoop Test has the names of colors printed in black and white (100 items to be named). The patient's basic score is the total time he/she takes to utter the 100 words on the card.
Time frame: Week 24
Score on Color Card of Stoop Test
The "color card" contains 100 patches of between 3-5 different colors. The patient's task is to utter the names of the colored patches as rapidly as possible, scanning the rows from left to right. The score is the total time (in seconds) it takes to utter the 100 colors.
Time frame: Week 0
Score on Color Card of Stoop Test
The "color card" contains 100 patches of between 3-5 different colors. The patient's task is to utter the names of the colored patches as rapidly as possible, scanning the rows from left to right. The score is the total time (in seconds) it takes to utter the 100 colors.
Time frame: Week 24
Score on Color Word Card of Stoop Test
The "color-word card" contains the printed names of colors, but printed in an ink of a conflicting color (e.g. the word RED might be printed in green, yellow, or blue). The patient is required to name the colors of the inks while ignoring the conflicting printed color names. The basic score is the total time (in seconds) to utter the 100 colors.
Time frame: Week 0
Score on Color Word Card of Stoop Test
The "color-word card" contains the printed names of colors, but printed in an ink of a conflicting color (e.g. the word RED might be printed in green, yellow, or blue). The patient is required to name the colors of the inks while ignoring the conflicting printed color names. The basic score is the total time (in seconds) to utter the 100 colors.
Time frame: Week 24
Score of Alcohol Subscale Within Addiction Severity Index (ASI) Scale
The Alcohol Subscale within ASI is one question that asks how bothered one has been by alcohol problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 24
Score of Drug Use Subscale Within Addiction Severity Index (ASI) Scale
The Drug Use Subscale within ASI is one question that asks how bothered one has been by drug use problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 0
Score of Drug Use Subscale Within Addiction Severity Index (ASI) Scale
The Drug Use Subscale within ASI is one question that asks how bothered one has been by drug use problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 24
Score of Social Relationship Subscale Within Addiction Severity Index (ASI) Scale
The Social Relationship Subscale within ASI contains 2 questions that ask how bothered one has been by family or social problems. The total range of the subscale is 0-8. The higher the score, the bigger the problem.
Time frame: Week 0
Score of Family / Social Relationship Subscale Within Addiction Severity Index (ASI) Scale
The Family / Social Relationship Subscale within ASI contains 2 questions that ask how bothered one has been by family or social problems. The total range of the subscale is 0-8. The higher the score, the bigger the problem.
Time frame: Week 24
Score of Legal Status Subscale Within Addiction Severity Index (ASI) Scale
The Legal Status Subscale within ASI is one question that asks how bothered one has been by legal problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 0
Score of Legal Status Subscale Within Addiction Severity Index (ASI) Scale
The Legal Status Subscale within ASI is one question that asks how bothered one has been by legal problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 24
Score of Medical Status Subscale Within Addiction Severity Index (ASI) Scale
The Medical Status Subscale within ASI is one question that asks how bothered one has been by medical problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 0
Score of Medical Status Subscale Within Addiction Severity Index (ASI) Scale
The Medical Status Subscale within ASI is one question that asks how bothered one has been by medical problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 24
Score of Psychiatric Status Subscale Within Addiction Severity Index (ASI) Scale
The Psychiatric Status Subscale within ASI is one question that asks how bothered one has been by psychiatric or emotional problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 0
Score of Psychiatric Status Subscale Within Addiction Severity Index (ASI) Scale
The Psychiatric Status Subscale within ASI is one question that asks how bothered one has been by psychiatric or emotional problems. The total range of the subscale is 0-4. The higher the score, the bigger the problem.
Time frame: Week 24
Score on EuroQOL EQ-5D Questionnaire
Problems related to drug abuse is assessed through this questionnaire, which consists of 5 conditions. Each condition is scored from 0-2 for a total score range of 0-10. The higher the score, the more problems.
Time frame: Week 0
Score on EuroQOL EQ-5D Questionnaire
Problems related to drug abuse is assessed through this questionnaire, which consists of 5 conditions. Each condition is scored from 0-2 for a total score range of 0-10. The higher the score, the more problems.
Time frame: Week 24
Alcohol Use Over Time, Drinks Per Day
Alcohol use over time, drinks per day
Time frame: Week 24
Other Drug Use Over Time, Cannabis, W0
Other drug use over time measuring cannabis at week 0
Time frame: week 0
Other Drug Use Over Time, Cannabis, W24
Other drug use over time measuring cannabis at week 24
Time frame: week 24
Other Drug Use Over Time, Cocaine, W0
Other drug use over time measuring cocaine at week 0
Time frame: week 0
Other Drug Use Over Time, Cocaine, W24
Other drug use over time measuring cocaine at week 0
Time frame: week 24
Other Drug Use Over Time, Stimulant, W0
Other drug use over time measuring stimulant (cocaine, crack and amphetamine) at week 0
Time frame: week 0
Other Drug Use Over Time, Stimulant, W24
Other drug use over time measuring stimulant (cocaine, crack and amphetamine) at week 24
Time frame: week 24
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