Opiate Addiction
Conditions
Keywords
opioid use disorder, syringe exchange, HIV risk reduction
Brief summary
This trial will recruit syringe exchange participants with opioid use disorder in New York City and test whether starting buprenorphine treatment at the syringe exchange program is more effective than referral to a community health center for buprenorphine treatment.
Detailed description
In a 24 week randomized controlled trial based in a large urban area with high rates of opioid use disorder (OUD) and HIV, 250 out-of-treatment opioid users who utilize syringe exchanges will be recruited and randomize to receive an onsite treatment intervention (O-BMT) or enhanced referral to buprenorphine treatment. Over 2 weeks, participants in the O-BMT arm will see a buprenorphine provider twice, receive weekly blister packs of medication, and then their care will be transferred to a community health center for maintenance buprenorphine treatment. In the control arm, participants will receive enhanced referral to the community health center for maintenance buprenorphine treatment. Data collection will include urine drug tests, questionnaires, and medical and pharmacy record review. Key outcomes will include engagement in buprenorphine treatment, treatment outcomes, and programmatic costs. Buprenorphine diversion will be assessed by using electronic monitors that estimate medication adherence, testing urine samples for buprenorphine, and through sequential surveys regarding buying or selling illicit buprenorphine.
Interventions
BEHAVIORALOnsite treatment
Participants will see a buprenorphine treatment provider who will assess for clinical criteria for opioid use disorder and write a prescription for buprenorphine treatment, which will be filled in a community pharmacy.
BEHAVIORALEnhanced referral
Participants will receive an expedited appointment at a community health center for evaluation for buprenorphine treatment
DRUGBuprenorphine
all participants will receive buprenorphine
Sponsors
National Institute on Drug Abuse (NIDA)
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomized 1:1 to receive the O-BMT intervention or enhanced referral
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. age ≥ 18 years 2. opioid use disorder 3. interest in buprenorphine treatment 4. motivation for opioid use disorder treatment 5. willingness to accept community health center referral 6. syringe exchange participant
Exclusion criteria
1. receiving opioid agonist treatment in the past 30 days (confirmed by New York Prescription Drug Monitoring Program); 2. inability to provide informed consent 3. unstable mental illness (e.g., suicidality, psychosis, etc.) 4. severe alcohol use disorder or benzodiazepine use disorder by the Diagnostic and Statistical Manual of Mental disorders, Fifth Edition (DSM-5) criteria 5. hypersensitivity to buprenorphine or naloxone. 6. pregnancy (confirmed via urine testing)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Buprenorphine Engagement | 30 days after randomization | Buprenorphine engagement was defined as the number of participants having an active buprenorphine prescription at 30 days after randomization. Responses were tallied using a dichotomous (i.e., Yes/No) measure. Data are summarized by study arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV Risk Behaviors | 6 months | Change in HIV risk behaviors will be assessed using the HIV risk behavior survey. This survey, consisting of a dichotomous (yes/no) measure of injection risk, will be used based on self-report of at least one risk behavior (sharing syringes, not using bleach to clean syringes, sharing cookers, or front/back loading of syringes) reported during the interval. The number of participants demonstrating at least one risk behavior is during the 6 month interval is summarized by study arm. |
| Buprenorphine Diversion | 6 months | Buprenorphine diversion will be defined as having at least one problem behavior: non-adherence to prescribed medication on electronic monitoring, self-reported diversion, or a urine sample consistent with diversion during the 6 month interval. This outcome measure is used to determine how many participants sell or give away prescribed medication. The number of participants with at least one problem behavior is summarized by study arm. |
| Incremental Cost-effectiveness Ratio (ICER) | 6 months | The ICER will be calculated by dividing the incremental mean cost of the O-BMT arm relative to the control arm by the incremental mean effectiveness of the O-BMT arm relative to the control arm. The primary economic effectiveness outcome will be the quality-adjusted life-year (QALY), a measure that incorporates both duration and health-related quality-of-life and is recommended as the primary economic effectiveness measure. ICER is a composite measure that incorporates QALYs (also reported as a separate outcome measure) and mean costs (also reported as a separate outcome measure). |
| Quality-adjusted Life-years (QALYs) Gained | 6 months | The main economic effectiveness outcome will be the quality-adjusted life-year (QALY), a measure that incorporates both duration and health-related quality-of-life and is recommended as the primary economic effectiveness measure. Mean years gained are summarized by study arm. |
| Treatment Retention | 6 months | Treatment retention was assessed by the number/percentage of participants who had a medical visit AND active buprenorphine prescription each month after buprenorphine initiation for 6 months. Results are summarized by study arm. |
| Time to First Buprenorphine Prescription | 1 month | Time to first buprenorphine prescription is defined as the amount of time, in days, from when a participant enrolled in the study to receipt of first buprenorphine prescription. Results are summarized by study arm using basic descriptive statistics. |
| Number/Percentage of Participants Who Received Any Buprenorphine Prescription | 6 months | The Number/percentage of participants who received any buprenorphine prescription is defined as the number/percentage of participants that filled at least one prescription for buprenorphine while enrolled in the study. Results are summarized by study arm. |
| Total Time Prescribed Buprenorphine | 6 months | Total time prescribed buprenorphine is defined as the amount of time in days that participants were prescribed buprenorphine during the study period. Results are summarized by study arm using basic descriptive statistics. |
| Mean Difference in Total Costs | 6 months | Mean cost (in US dollars) of the O-BMT arm were compared to the control arm. The resource utilization and resulting cost of implementing and administering the O-BMT intervention were estimated using microcosting analysis and participant self-report. Mean costs (in US dollars) are summarized by study arm. |
Countries
United States
Participant flow
Pre-assignment details
211 participants were screened and 97 were randomized into the study. Of the 114 participants who were not enrolled into the study, 98 participants did not meet all of the eligibility criteria, 13 did not show up for the enrollment visit and 3 participants signed the informed consent form but were not randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| O-BMT (Onsite Treatment) Over 2 weeks at the syringe-exchange program, participants in the O-BMT arm will see a buprenorphine provider twice, receive weekly blister packs of medication, and then their care will be transferred to a community health center for maintenance buprenorphine treatment
Onsite treatment: Participants will see a buprenorphine treatment provider who will assess for clinical criteria for opioid use disorder and write a prescription for buprenorphine treatment, which will be filled in a community pharmacy.
Buprenorphine: all participants will receive buprenorphine | 48 |
| Enhanced Referral In the control arm, participants will receive enhanced referral to a community health center for maintenance buprenorphine treatment
Enhanced referral: Participants will receive an expedited appointment at a community health center for evaluation for buprenorphine treatment
Buprenorphine: all participants will receive buprenorphine | 49 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 13 | 5 |
Baseline characteristics
| Characteristic | Enhanced Referral | Total | O-BMT (Onsite Treatment) |
|---|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 11.3 | 42.0 years STANDARD_DEVIATION 10.6 | 40.6 years STANDARD_DEVIATION 9.9 |
| Alcohol Use | 1.3 days STANDARD_DEVIATION 2.5 | 1.4 days STANDARD_DEVIATION 3.7 | 1.6 days STANDARD_DEVIATION 4.9 |
| Amphetamine Use | 0.9 days STANDARD_DEVIATION 4.4 | 0.6 days STANDARD_DEVIATION 2.7 | 0.2 days STANDARD_DEVIATION 0.8 |
| Buprenorphine Use | 16 Participants | 35 Participants | 19 Participants |
| Cocaine Use | 12.6 days STANDARD_DEVIATION 12.2 | 11.3 days STANDARD_DEVIATION 11.8 | 10.0 days STANDARD_DEVIATION 11.4 |
| Heroin use | 24.2 days STANDARD_DEVIATION 10.1 | 23.8 days STANDARD_DEVIATION 10.7 | 23.3 days STANDARD_DEVIATION 11.3 |
| Intravenous Drug Use | 33 Participants | 61 Participants | 28 Participants |
| Mental Health Condition | 22 Participants | 44 Participants | 22 Participants |
| Methadone Use | 0.6 days STANDARD_DEVIATION 1.7 | 1.3 days STANDARD_DEVIATION 4.5 | 2.0 days STANDARD_DEVIATION 7.3 |
| Opioid or Analgesic Use | 3.3 days STANDARD_DEVIATION 8.4 | 3.3 days STANDARD_DEVIATION 8.4 | 3.3 days STANDARD_DEVIATION 8.5 |
| Opioid Use Disorder (OUD) Criteria | 10.8 criteria STANDARD_DEVIATION 2.2 | 10.7 criteria STANDARD_DEVIATION 2.2 | 10.5 criteria STANDARD_DEVIATION 2.1 |
| Polysubstance Use | 12.0 days STANDARD_DEVIATION 13.3 | 11.5 days STANDARD_DEVIATION 12.8 | 11.0 days STANDARD_DEVIATION 12.3 |
| Race/Ethnicity, Customized Hispanic Black | 4 Participants | 16 Participants | 12 Participants |
| Race/Ethnicity, Customized Hispanic Other | 14 Participants | 27 Participants | 13 Participants |
| Race/Ethnicity, Customized Hispanic White | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 10 Participants | 16 Participants | 6 Participants |
| Race/Ethnicity, Customized Non-Hispanic Other | 4 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 13 Participants | 24 Participants | 11 Participants |
| Region of Enrollment United States | 49 participants | 97 participants | 48 participants |
| Sex/Gender, Customized Female | 10 Participants | 19 Participants | 9 Participants |
| Sex/Gender, Customized Male | 38 Participants | 76 Participants | 38 Participants |
| Sex/Gender, Customized Refuse to answer | 0 Participants | 1 Participants | 1 Participants |
| Sex/Gender, Customized Transgender | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 49 |
| other Total, other adverse events | 2 / 48 | 1 / 49 |
| serious Total, serious adverse events | 1 / 48 | 2 / 49 |
Outcome results
Primary
Buprenorphine Engagement
Buprenorphine engagement was defined as the number of participants having an active buprenorphine prescription at 30 days after randomization. Responses were tallied using a dichotomous (i.e., Yes/No) measure. Data are summarized by study arm.
Time frame: 30 days after randomization
Population: Intention to treat (ITT) analysis design. All participants, including those who are lost to follow-up, are included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | Buprenorphine Engagement | 19 Participants |
| Enhanced Referral | Buprenorphine Engagement | 19 Participants |
p-value: 0.94Chi-squared
Secondary
Buprenorphine Diversion
Buprenorphine diversion will be defined as having at least one problem behavior: non-adherence to prescribed medication on electronic monitoring, self-reported diversion, or a urine sample consistent with diversion during the 6 month interval. This outcome measure is used to determine how many participants sell or give away prescribed medication. The number of participants with at least one problem behavior is summarized by study arm.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | Buprenorphine Diversion | 8 Participants |
| Enhanced Referral | Buprenorphine Diversion | 2 Participants |
p-value: 0.051Fisher Exact
Secondary
HIV Risk Behaviors
Change in HIV risk behaviors will be assessed using the HIV risk behavior survey. This survey, consisting of a dichotomous (yes/no) measure of injection risk, will be used based on self-report of at least one risk behavior (sharing syringes, not using bleach to clean syringes, sharing cookers, or front/back loading of syringes) reported during the interval. The number of participants demonstrating at least one risk behavior is during the 6 month interval is summarized by study arm.
Time frame: 6 months
Population: HIV Risk behavior data was unable to be collected from 12 participants in the onsite buprenorphine treatment (O-BMT) study arm and 9 participants in the Enhanced referral study arm. Accordingly, there is no HIV risk behavior data to report for these participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | HIV Risk Behaviors | 5 Participants |
| Enhanced Referral | HIV Risk Behaviors | 4 Participants |
p-value: 0.613295% CI: [0.347, 6.018]Regression, Logistic
Secondary
Incremental Cost-effectiveness Ratio (ICER)
The ICER will be calculated by dividing the incremental mean cost of the O-BMT arm relative to the control arm by the incremental mean effectiveness of the O-BMT arm relative to the control arm. The primary economic effectiveness outcome will be the quality-adjusted life-year (QALY), a measure that incorporates both duration and health-related quality-of-life and is recommended as the primary economic effectiveness measure. ICER is a composite measure that incorporates QALYs (also reported as a separate outcome measure) and mean costs (also reported as a separate outcome measure).
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| O-BMT (Onsite Treatment) | Incremental Cost-effectiveness Ratio (ICER) | -805067 Ratio (US dollars/QALY) |
Secondary
Mean Difference in Total Costs
Mean cost (in US dollars) of the O-BMT arm were compared to the control arm. The resource utilization and resulting cost of implementing and administering the O-BMT intervention were estimated using microcosting analysis and participant self-report. Mean costs (in US dollars) are summarized by study arm.
Time frame: 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| O-BMT (Onsite Treatment) | Mean Difference in Total Costs | 2702.43 US Dollars |
| Enhanced Referral | Mean Difference in Total Costs | 26853.97 US Dollars |
p-value: <0.01non-parametric bootstrapping
Secondary
Number/Percentage of Participants Who Received Any Buprenorphine Prescription
The Number/percentage of participants who received any buprenorphine prescription is defined as the number/percentage of participants that filled at least one prescription for buprenorphine while enrolled in the study. Results are summarized by study arm.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | Number/Percentage of Participants Who Received Any Buprenorphine Prescription | 36 Participants |
| Enhanced Referral | Number/Percentage of Participants Who Received Any Buprenorphine Prescription | 29 Participants |
p-value: 0.098Chi-squared
Secondary
Quality-adjusted Life-years (QALYs) Gained
The main economic effectiveness outcome will be the quality-adjusted life-year (QALY), a measure that incorporates both duration and health-related quality-of-life and is recommended as the primary economic effectiveness measure. Mean years gained are summarized by study arm.
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| O-BMT (Onsite Treatment) | Quality-adjusted Life-years (QALYs) Gained | 0.20 years gained |
| Enhanced Referral | Quality-adjusted Life-years (QALYs) Gained | 0.17 years gained |
p-value: 0.1non-parametric bootstrapping
Secondary
Time to First Buprenorphine Prescription
Time to first buprenorphine prescription is defined as the amount of time, in days, from when a participant enrolled in the study to receipt of first buprenorphine prescription. Results are summarized by study arm using basic descriptive statistics.
Time frame: 1 month
Population: Time to first buprenorphine prescription results data was only available, and reported, from the sub-group of participants that received a prescription.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| O-BMT (Onsite Treatment) | Time to First Buprenorphine Prescription | 3.0 days | Standard Deviation 4.6 |
| Enhanced Referral | Time to First Buprenorphine Prescription | 14.0 days | Standard Deviation 20.9 |
p-value: 0.011t-test, 2 sided
Secondary
Total Time Prescribed Buprenorphine
Total time prescribed buprenorphine is defined as the amount of time in days that participants were prescribed buprenorphine during the study period. Results are summarized by study arm using basic descriptive statistics.
Time frame: 6 months
Population: Total time prescribed buprenorphine results data was only available, and reported, from the sub-group of participants that received a prescription.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| O-BMT (Onsite Treatment) | Total Time Prescribed Buprenorphine | 46.7 days | Standard Deviation 32.9 |
| Enhanced Referral | Total Time Prescribed Buprenorphine | 56.6 days | Standard Deviation 34.8 |
p-value: 0.256t-test, 2 sided
Secondary
Treatment Retention
Treatment retention was assessed by the number/percentage of participants who had a medical visit AND active buprenorphine prescription each month after buprenorphine initiation for 6 months. Results are summarized by study arm.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | Treatment Retention | 2 Participants |
| Enhanced Referral | Treatment Retention | 6 Participants |
p-value: 0.148Chi-squared
Post Hoc
Buprenorphine Adherence (Confirmed)
Buprenorphine Adherence (confirmed) was defined as meeting the primary outcome and having a urine drug screen positive for buprenorphine at 30 days. This outcome was assessed as a composite measure for sensitivity analysis. The number of participants who both maintained an active buprenorphine prescription at 30 days after randomization, based on a dichotomous (i.e., Yes/No) measure, AND tested positive for Buprenorphine in their urine sample following the 30-day period were tabulated. Data are summarized by study arm.
Time frame: 30 days after randomization
Population: Urine samples were unable to be collected from 26 participants in the onsite buprenorphine treatment (O-BMT) study arm and 23 participants in the Enhanced Referral study arm. As such, an assessment was unable to be made for these participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | Buprenorphine Adherence (Confirmed) | 5 Participants |
| Enhanced Referral | Buprenorphine Adherence (Confirmed) | 8 Participants |
Post Hoc
Buprenorphine Adherence (Self-reported)
Buprenorphine Adherence (self-reported), defined as meeting the primary outcome of buprenorphine engagement and self-reporting buprenorphine use at 30 days, was assessed as a composite measure for sensitivity analysis. The number of participants who both maintained an active buprenorphine prescription at 30 days after randomization, based on a dichotomous (i.e., Yes/No) measure, AND self-reported having taken buprenorphine on 1 or more days during the 30-day period were tabulated. Data are summarized by study arm.
Time frame: 30 days after randomization
Population: Self-reported buprenorphine use data was unable to be collected from 20 participants in the onsite buprenorphine treatment (O-BMT) study arm and 15 participants in the Enhanced referral study arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| O-BMT (Onsite Treatment) | Buprenorphine Adherence (Self-reported) | 13 Participants |
| Enhanced Referral | Buprenorphine Adherence (Self-reported) | 13 Participants |