Opiate Dependence
Conditions
Keywords
Buprenorphine, Buprenorphine/naloxone, Counseling, Primary care
Brief summary
The aim of the study is to determine whether buprenorphine/naloxone maintenance versus detoxification using buprenorphine/naloxone, in prescription opioid dependent patients receiving primary care management and drug counseling in an office-based setting, leads to decreased illicit opioid use.
Detailed description
Prescription opioid dependence is increasing and creates a significant public health burden, but office-based physicians lack evidence-based guidelines to decide between maintenance or detoxification treatment with buprenorphine/naloxone. The proposed study compares buprenorphine/naloxone maintenance (Mtn) vs. detoxification (Dtx) in a 18-week randomized clinical trail in a heterogeneous population of prescription opioid dependent patients (N=120) in a primary care clinic. Patients are randomized to Mtn or Dtx after a 2-week induction period. Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, buprenorphine/naloxone will continue unchanged for the remainder of the study. In Dtx, the dosage of buprenorphine/naloxone will be tapered to zero over the next 3 weeks, and patients will not receive additional buprenorphine/naloxone for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup. The study will test the hypothesis that Mtn will lead to decreased illicit drug use and will demonstrate incremental cost-effectiveness compared to Dtx. Relevance to public health: The results of this study will help define the role of maintenance vs. detoxification with buprenorphine/naloxone in the care of prescription opioid dependent patients in primary care.
Interventions
BEHAVIORALBehavioral: Buprenorphine/naloxone maintenance (Mtn)
Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
BEHAVIORALBehavioral: Buprenorphine/naloxone detoxification (Dtx)
Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* opioid dependence
Exclusion criteria
* current dependence on alcohol, cocaine, benzodiazepines or sedatives * current suicide or homicide risk * current psychotic disorder or untreated major depression * inability to read or understand English * life-threatening or unstable medical problems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Illicit Opioid Use | 18 weeks | Urinalysis based on scheduled weekly urine screenings during treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention in Treatment | 18 weeks | Mean number of days from randomization to last clinical contact |
| Reduction in Cocaine Use | 18 weeks | As measured by the percent of provided urines positive for cocaine |
| Proportion of Patients Protectively Transferred | 18 weeks | \>= 2 consecutive weeks of daily illicit opioid use and opioid positive urine samples after completion of the first 6 weeks of the study |
| Patient Satisfaction | 18 weeks | Patient satisfaction as measured by survey. Primary Care Buprenorphine Satisfaction Scale (PCBSS). Comprises of 19 items evaluating satisfaction with staff expertise, concern, and responsiveness. Range of scores from 15-95. I higher score indicates greater satisfaction. |
| Health Status | 18 weeks | Measured by the SF-36 overall transformed measure. In the SF-36 all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. |
| Changes in HIV Risk | Baseline and 18 weeks | As measured by the AIDS Risk Inventory. The AIDS Risk Inventory (ARI) is a 166 item structured interview that assesses the number and frequency of drug-related and sexual risk behaviors in the preceding 3 months. Calculation of the ARI total score is based on the frequency of occurrence of a given behavior and on the recency of this behavior, with recency being weighted more than a life-time occurrence of the same behavior. Higher values are associated with greater risk of HIV transmission (worse). There are 10 subscales comprised of between 8 and 24 items. Subscales scores are based on the sum of the individual items and the overall ARI total score is the sum of the subscales. Scores can range from 0 to 350, although among opioid dependent patients most values are below 100 with means between 50 and 60 depending on characteristics of the patients and treatment status. |
Countries
United States
Participant flow
Pre-assignment details
289 Patients underwent assessment for eligibility, 29 did not meet inclusion criteria, 132 lost contact or chose other treatment, and 15 did not complete induction
Participants by arm
| Arm | Count |
|---|---|
| Taper Condition Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone.
Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup. | 57 |
| Maintenance Condition Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services.
Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. | 56 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Became pregnant and transferred care | 0 | 1 |
| Overall Study | Met criteria for protective transfer | 16 | 3 |
| Overall Study | Missed 3 physician management visits | 1 | 0 |
| Overall Study | Missed Medication > 1 wk | 34 | 15 |
Baseline characteristics
| Characteristic | Taper Condition | Maintenance Condition | Total |
|---|---|---|---|
| Age, Continuous | 30.3 years STANDARD_DEVIATION 8.8 | 30.5 years STANDARD_DEVIATION 9.8 | 30.4 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 52 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 56 Participants | 52 Participants | 108 Participants |
| Sex: Female, Male Female | 23 Participants | 25 Participants | 48 Participants |
| Sex: Female, Male Male | 34 Participants | 31 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 57 | 0 / 56 |
| serious Total, serious adverse events | 0 / 57 | 0 / 56 |
Outcome results
Primary
Illicit Opioid Use
Urinalysis based on scheduled weekly urine screenings during treatment period
Time frame: 18 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Taper Condition | Illicit Opioid Use | 35.2 percent of opioid negative urine samples |
| Maintenance Condition | Illicit Opioid Use | 53.2 percent of opioid negative urine samples |
Secondary
Changes in HIV Risk
As measured by the AIDS Risk Inventory. The AIDS Risk Inventory (ARI) is a 166 item structured interview that assesses the number and frequency of drug-related and sexual risk behaviors in the preceding 3 months. Calculation of the ARI total score is based on the frequency of occurrence of a given behavior and on the recency of this behavior, with recency being weighted more than a life-time occurrence of the same behavior. Higher values are associated with greater risk of HIV transmission (worse). There are 10 subscales comprised of between 8 and 24 items. Subscales scores are based on the sum of the individual items and the overall ARI total score is the sum of the subscales. Scores can range from 0 to 350, although among opioid dependent patients most values are below 100 with means between 50 and 60 depending on characteristics of the patients and treatment status.
Time frame: Baseline and 18 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Taper Condition | Changes in HIV Risk | Baseline | 66.7 units on a scale | Standard Deviation 25.6 |
| Taper Condition | Changes in HIV Risk | 18 weeks | 74.5 units on a scale | Standard Deviation 19.4 |
| Maintenance Condition | Changes in HIV Risk | Baseline | 67.6 units on a scale | Standard Deviation 25.7 |
| Maintenance Condition | Changes in HIV Risk | 18 weeks | 74.4 units on a scale | Standard Deviation 18 |
Secondary
Health Status
Measured by the SF-36 overall transformed measure. In the SF-36 all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.
Time frame: 18 weeks
Population: Results are provided on those individuals who completed this assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Taper Condition | Health Status | Baseline | 67.2 units on a scale | Standard Deviation 20.4 |
| Taper Condition | Health Status | In-Treatment | 68.7 units on a scale | Standard Deviation 30.5 |
| Maintenance Condition | Health Status | Baseline | 67.6 units on a scale | Standard Deviation 18.6 |
| Maintenance Condition | Health Status | In-Treatment | 66.6 units on a scale | Standard Deviation 21.9 |
Secondary
Patient Satisfaction
Patient satisfaction as measured by survey. Primary Care Buprenorphine Satisfaction Scale (PCBSS). Comprises of 19 items evaluating satisfaction with staff expertise, concern, and responsiveness. Range of scores from 15-95. I higher score indicates greater satisfaction.
Time frame: 18 weeks
Population: Results are provided on those individuals who completed this assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Taper Condition | Patient Satisfaction | 78.7 units on a scale |
| Maintenance Condition | Patient Satisfaction | 79.9 units on a scale |
Secondary
Proportion of Patients Protectively Transferred
\>= 2 consecutive weeks of daily illicit opioid use and opioid positive urine samples after completion of the first 6 weeks of the study
Time frame: 18 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Taper Condition | Proportion of Patients Protectively Transferred | 16 participants |
| Maintenance Condition | Proportion of Patients Protectively Transferred | 3 participants |
Secondary
Reduction in Cocaine Use
As measured by the percent of provided urines positive for cocaine
Time frame: 18 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Taper Condition | Reduction in Cocaine Use | 11.5 percent of cocaine positive urines | Standard Deviation 25.9 |
| Maintenance Condition | Reduction in Cocaine Use | 11.1 percent of cocaine positive urines | Standard Deviation 23.5 |
Secondary
Retention in Treatment
Mean number of days from randomization to last clinical contact
Time frame: 18 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Taper Condition | Retention in Treatment | 57.5 number of days |
| Maintenance Condition | Retention in Treatment | 98.7 number of days |