Opiate Dependence, Opioid-related Disorders, Substance-related Disorders
Conditions
Keywords
Opiate Analgesic Dependence
Brief summary
The purpose of this study is to determine whether treatment outcome for subjects dependent on prescription opioid analgesics can be improved by adding individual drug counseling to the prescription of buprenorphine/naloxone with standard medical management. This will be examined during: a) an initial four-week treatment with taper; b) a 12-week stabilization treatment for those who do not respond successfully to the initial treatment; and c) a long-term follow-up assessment at 1.5 years, 2.5 years, and 3.5 years after treatment.
Detailed description
This is a randomized 2-phase, open-label; multi-center study conducted in outpatient treatment settings. The main objective of this study is to identify an effective sublingual buprenorphine/naloxone treatment regimen for subjects dependent on prescription opioids. Phase 1 of this study will assess the prevailing one-month detoxification practice. This phase will assess the benefits of individual drug counseling in a short-term treatment paradigm. The second phase of this study will assess the benefit of individual drug counseling in a longer-term treatment paradigm for participants who did not respond successfully to the short-term buprenorphine/naloxone treatment. There is also a long-term follow-up assessment to determine outcomes at 1.5 years, 2.5 years, and 3.5 years after treatment.
Interventions
BEHAVIORALStandard Medical Management (SMM) of Prescription Opiate Abuse
Standard Medical Management in Phase 1 will consist of one hour-long initial visit; one individual 15-20 minute visit later in Week 1; one individual 15-20 minute visit per week through the end of Week 4; one 15-20 minute SMM visit at Week 6 and at Week 8. And in Phase 2, one 30-60 minute initial visit; one 15-20 minute follow-up visit later in Week 1; one individual session (15-20 minutes) per week through Week 12. In addition, participants in Phase 1 will receive BUP/NX at between 8 to 32mg/day; tapering to zero between weeks three and four. Those referred to Phase 2 will receive up to 32 mg/day for three months tapering to zero during month four.
BEHAVIORALEnhanced Medical Management (EMM) of Prescription Opiate Abuse
Enhanced Medical Management in Phase 1 will consist of SMM plus two individual sessions with a counselor per week (45 minutes each) through Weeks 1-4, and one 45-minute counseling visit at Week 6 and at Week 8. And in Phase 2, EMM will consist of the SMM plus two individual sessions with a counselor per week (45 minutes each) during Weeks 1-6 and one individual session with a counselor per week (45 minutes each) during Weeks 7-12. In addition, participants in Phase 1 will receive BUP/NX at between 8 to 32mg/day; tapering to zero between weeks three and four. Those referred to Phase 2 will receive up to 32 mg/day for three months tapering to zero during month four.
Sponsors
University of California, Los Angeles
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years old or older * Physically dependent on opioids * Meet DSM-IV criteria for opioid dependence
Exclusion criteria
* Known allergy or sensitivity to buprenorphine or naloxone * Unstable psychiatric disorder * Pregnant or lactating females * Liver function test results greater than 5 times the upper limit of normal range
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition at End of Phase 1 | 12 weeks | In Phase 1, successful outcome was defined as completing week 12 with self-reported opioid use on no more than 4 days in a month, absence of 2 consecutive opioid-positive urine test results, no additional substance use disorder treatment (other than self-help), and no more than 1 missing urine sample during the 12 weeks. |
| The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition, Phase 2 End of Treatment | 12 weeks in Phase 2 period (i.e., 24 weeks into the study) | In phase 2, successful outcome was defined as abstaining from opioids during week 12 (the final week of buprenorphine-naloxone stabilization) and during at least 2 of the previous 3 weeks (weeks 9-11). This outcome measure required substantial improvement but not complete abstinence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 2 by Chronic Pain Condition | 12 weeks | As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain other than everyday kinds of pain excluding withdrawal-related pain, for at least 3 months. |
| The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition Phase 2, 8-week Posttreatment Follow-up | 24 weeks in Phase 2 period (i.e., 36 weeks into the study) | A planned secondary outcome, successful outcome at week 24, that is, 8 weeks after completion of buprenorphine-naloxone taper, was defined the same as at week 12 of Phase 2, that is abstinent from opioids during week 24 and at least 2 of the previous 3 weeks. |
| The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 2 | 12 weeks | As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome. |
| The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 1 | 12 weeks | As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome. |
| The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 1 by Chronic Pain Condition | 12 weeks | As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain other than everyday kinds of pain excluding withdrawal-related pain, for at least 3 months. |
Countries
United States
Participant flow
Recruitment details
653 treatment-seeking outpatients dependent on prescription opioids across 10 U.S. sites.
Participants by arm
| Arm | Count |
|---|---|
| Buprenorphine/Nx With EMM All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional. | 329 |
| Buprenorphine/Nx With SMM All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine. | 324 |
| Total | 653 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase 1 (12 Weeks) | Eligible for Phase 2 | 220 | 225 |
| Phase 1 (12 Weeks) | Investigator-initiated termination | 2 | 0 |
| Phase 1 (12 Weeks) | Lost to Follow-up | 88 | 75 |
| Phase 2 (24 Weeks) | Discontinued intervention (jailed) | 0 | 1 |
| Phase 2 (24 Weeks) | Lost to Follow-up prior to wk 13 | 19 | 18 |
Baseline characteristics
| Characteristic | Buprenorphine/Nx With SMM | Buprenorphine/Nx With EMM | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 324 Participants | 329 Participants | 653 Participants |
| Age Continuous | 33.5 years STANDARD_DEVIATION 10.3 | 32.9 years STANDARD_DEVIATION 10.1 | 33.2 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment United States | 324 participants | 329 participants | 653 participants |
| Sex: Female, Male Female | 136 Participants | 125 Participants | 261 Participants |
| Sex: Female, Male Male | 188 Participants | 204 Participants | 392 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 277 / 329 | 265 / 324 |
| serious Total, serious adverse events | 6 / 329 | 5 / 324 |
Outcome results
Primary
The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition at End of Phase 1
In Phase 1, successful outcome was defined as completing week 12 with self-reported opioid use on no more than 4 days in a month, absence of 2 consecutive opioid-positive urine test results, no additional substance use disorder treatment (other than self-help), and no more than 1 missing urine sample during the 12 weeks.
Time frame: 12 weeks
Population: 653 study participants randomized to Phase 1 were included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition at End of Phase 1 | 19 participants |
| Buprenorphine/Nx With SMM | The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition at End of Phase 1 | 24 participants |
Primary
The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition, Phase 2 End of Treatment
In phase 2, successful outcome was defined as abstaining from opioids during week 12 (the final week of buprenorphine-naloxone stabilization) and during at least 2 of the previous 3 weeks (weeks 9-11). This outcome measure required substantial improvement but not complete abstinence.
Time frame: 12 weeks in Phase 2 period (i.e., 24 weeks into the study)
Population: 360 participants randomized to Phase 2 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition, Phase 2 End of Treatment | 93 participants |
| Buprenorphine/Nx With SMM | The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition, Phase 2 End of Treatment | 84 participants |
Secondary
The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition Phase 2, 8-week Posttreatment Follow-up
A planned secondary outcome, successful outcome at week 24, that is, 8 weeks after completion of buprenorphine-naloxone taper, was defined the same as at week 12 of Phase 2, that is abstinent from opioids during week 24 and at least 2 of the previous 3 weeks.
Time frame: 24 weeks in Phase 2 period (i.e., 36 weeks into the study)
Population: 360 participants randomized to Phase 2 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition Phase 2, 8-week Posttreatment Follow-up | 18 participants |
| Buprenorphine/Nx With SMM | The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition Phase 2, 8-week Posttreatment Follow-up | 13 participants |
Secondary
The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 1 by Chronic Pain Condition
As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain other than everyday kinds of pain excluding withdrawal-related pain, for at least 3 months.
Time frame: 12 weeks
Population: 379 identified as having chronic pain at baseline in Phase 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 1 by Chronic Pain Condition | 30 participants |
| Buprenorphine/Nx With SMM | The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 1 by Chronic Pain Condition | 13 participants |
Secondary
The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 2 by Chronic Pain Condition
As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain other than everyday kinds of pain excluding withdrawal-related pain, for at least 3 months.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 2 by Chronic Pain Condition | 79 participants |
| Buprenorphine/Nx With SMM | The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 2 by Chronic Pain Condition | 98 participants |
Secondary
The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 1
As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome.
Time frame: 12 weeks
Population: Participants randomized to Phase 1 were stratified by two variables: current chronic pain and lifetime heroin use.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 1 | 9 participants |
| Buprenorphine/Nx With SMM | The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 1 | 34 participants |
Secondary
The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 2
As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine/Nx With EMM | The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 2 | 37 participants |
| Buprenorphine/Nx With SMM | The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 2 | 140 participants |