Hiv, Opioid-use Disorder
Conditions
Brief summary
The Primary Objective of this study is to compare the effectiveness of HIV clinic-based extended-release Naltrexone (XR-NTX) in decreasing substance use and increasing HIV viral suppression in HIV-infected participants with opioid use disorder to Treatment as Usual in this population.
Detailed description
The CTN-0055 CHOICES pilot study demonstrated the feasibility of extended-release naltrexone (XR-NTX) for treatment of opioid use disorder in HIV primary care. The CTN-0067 CHOICES scale-up study builds on lessons learned from the pilot and uses the Consolidated Framework for Implementation Research to advance understanding of XR-NTX adoption in HIV primary care clinics. The study is an open-label, randomized, comparative effectiveness trial of office-based XR-NTX for 24 weeks (6 monthly injections) versus treatment as usual (TAU) in HIV-infected participants with untreated opioid use disorder. Each participant will be engaged in the overall study for 25 to 28 weeks, depending on the speed of screening and enrollment procedures.
Interventions
DRUGNaltrexone Injectable Suspension
Six monthly injections of extended-release naltrexone
OTHERTreatment as usual
Standard treatment for opioid use disorder provided at each HIV clinic
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
University of Kentucky
Jackson Health System
Tarzana Treatment Centers
Ruth M. Rothstein CORE Center
Oregon Health and Science University
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
* Participant is at least 18 years old * Participant has provided written informed consent and HIPAA for medical record abstraction * Participant meets Diagnostic and Statistical (DSM)-5 criteria for moderate or severe opioid use disorder * Willing to be randomized to antagonist-based therapy or TAU for treatment of opioid use disorder * Has an HIV viral RNA count of greater than 200 copies/ml (not clinically suppressed) * Willing to establish ongoing HIV care at the site if not already receiving ongoing care * If female, willing to take at least one evidence-based measure to avoid becoming pregnant
Exclusion criteria
* Participant has a serious medical, psychiatric, or substance use disorder that, in the opinion of the study physician, would make participation hazardous to the participant, compromise study findings, or prevent participant from completing the study. Examples include: * Acutely life-threatening medical illnesses (e.g., active opportunistic infection, uncompensated heart failure, end-stage liver disease, acute hepatitis and moderate to severe renal impairment) as assessed by medical history, review of symptoms, physical exam and/or laboratory assessments * Severe, inadequately treated mental health disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview * Suicidal or homicidal ideation requiring immediate attention * Participant has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) liver enzymes greater than five times the upper limit of normal on screening phlebotomy * Participant has an international normalized ratio (INR) \> 1.5 or platelet count \<100k * Participant has a known allergy or sensitivity to naloxone, naltrexone, polyactide-co-glycolide, carboxymethylcellulose, or other components of the Vivitrol diluent * Anticipate undergoing surgery during study participation * Have chronic pain requiring ongoing pain management with opioid analgesics * If female, currently (at time of consent) pregnant or breastfeeding or planning on conceiving in the coming months * Body habitus that, in the judgment of the study physician, precludes safe intramuscular injection on XR-NTX (e.g., excess fat tissue over the buttocks) * Received methadone of buprenorphine maintenance therapy for treatment of opioid dependence in the 4 weeks prior to screening * Have taken an investigational drug in another study within 30 days of study consent * Have had treatment with XR-NTX for opioid or alcohol dependence in the 4 weeks prior to consent * Are currently in jail, prison or have a pending legal action which may prevent an individual from completing the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HIV Viral Suppression, Missing Imputed as Unsuppressed | 12 weeks and 24 weeks | HIV-1 RNA \<200 copies/ml |
| Number of Participants With HIV Viral Suppression, Complete Case | 12 weeks and 24 weeks | HIV-1 RNA \<200 copies/ml |
| Number of Participants With HIV Viral Suppression, Per-protocol | 12 weeks and 24 weeks | HIV-1 RNA \<200 copies/ml |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Engagement in HIV Care: 100% Antiretroviral Therapy Adherence | 24 weeks | Number of participants taking 100% of prescribed ART doses in the past month at 24 weeks for those prescribed ART at any point during the 24 week trial (proportion; self-reported medication adherence measure). Chi-squared test comparing proportion to treatment assignment, for those prescribed ART. |
| Number of Participants With at Least 1 HIV Care Visit in Past 12 Weeks | 24 weeks | At least 1 HIV care visit in past 12 weeks |
| Number of Participants Who Had Unprotected Sex in Past 30 Days | Baseline and 24 weeks | Past 30 day unprotected sex, as measured by the Risk Assessment Battery at baseline and week 24 (binary; self-report). |
| Veterans Aging Cohort Study (VACS) Index | Baseline and 24 weeks | Absolute value of participant VACS Index at baseline and 24 weeks Veterans Aging Cohort Study Index Minimum value: 0 Maximum value: 164 A higher score means a worse outcome. |
| Engagement in HIV Care: Quality of Life | Baseline and 24 weeks | Past 30 day health-related quality of life as measured by the EQ-5D questionnaire at baseline and week 24. Minimum value: 0 Maximum value: 100 Higher scores mean a better outcome |
| Average Number of Self-Reported Days of Opioid Use in Last 30 Days | Between baseline and 24 weeks | Average number of days of opioid use between baseline and 24 weeks, measured by the Timeline Follow-Back (count; self-report), will be used to compare opioid use by treatment group. Confirmatory analysis will assess opioid use by the average number of days of opioid use in the last 30 days of the study (by Addiction Severity Index-lite; count; self-report) and the number of monthly urine drug screen (UDS) negative for opioids between baseline and 24 weeks (count; laboratory data). |
| Number of Participants Who Test Positive for Opioids at 24 Weeks | 24 weeks | Number and percent of participants with UDS positive for opioids at 24 weeks. |
| Number of Participants With Multiple Sex Partners in Past 30 Days | Baseline and 24 weeks | Past 30 day multiple sex partners, as measured by the Risk Assessment Battery at baseline and week 24 (binary; self-report). |
| CD4 Count | Baseline and 24 weeks | Cluster of Differentiation 4 Absolute value of CD4 count at baseline and 24 weeks. |
| Engagement in HIV Care: Antiretroviral Therapy Prescribed | Baseline and 24 weeks | Absolute value of participants prescribed ART at baseline and within 24 weeks following randomization. Each individual can be scored 0 (not prescribed ART) or 1 (prescribed ART) at both baseline and follow-up, after which his or her outcome score will be the follow-up score minus the baseline score. Outcomes will be analyzed via rank-based methods such as Wilcoxon rank-sum tests. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Extended-release Naltrexone (XR-NTX) Extended-release naltrexone
Naltrexone Injectable Suspension: Six monthly injections of extended-release naltrexone | 55 |
| Treatment as Usual (TAU) Treatment as usual
Treatment as usual: Standard treatment for opioid use disorder provided at each HIV clinic | 59 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Incarcerated | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Extended-release Naltrexone (XR-NTX) | Treatment as Usual (TAU) | Total |
|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 10.8 | 46 years STANDARD_DEVIATION 11.5 | 47 years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 54 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV Viral Load | 4.0 log10 copies/mL STANDARD_DEVIATION 0.9 | 4.0 log10 copies/mL STANDARD_DEVIATION 1.1 | 4.0 log10 copies/mL STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 34 Participants | 64 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 | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) White | 19 Participants | 23 Participants | 42 Participants |
| Sex: Female, Male Female | 23 Participants | 20 Participants | 43 Participants |
| Sex: Female, Male Male | 32 Participants | 39 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 55 | 1 / 59 |
| other Total, other adverse events | 11 / 55 | 7 / 59 |
| serious Total, serious adverse events | 5 / 55 | 7 / 59 |
Outcome results
Primary
Number of Participants With HIV Viral Suppression, Complete Case
HIV-1 RNA \<200 copies/ml
Time frame: 12 weeks and 24 weeks
Population: Non-inferiority analyses of HIV viral suppression by treatment arm Complete case: Includes 81 participants with non-missing viral load data at 12 and 24 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants With HIV Viral Suppression, Complete Case | 12 Weeks | 23 Participants |
| Extended-release Naltrexone (XR-NTX) | Number of Participants With HIV Viral Suppression, Complete Case | 24 Weeks | 26 Participants |
| Treatment as Usual (TAU) | Number of Participants With HIV Viral Suppression, Complete Case | 12 Weeks | 19 Participants |
| Treatment as Usual (TAU) | Number of Participants With HIV Viral Suppression, Complete Case | 24 Weeks | 26 Participants |
Primary
Number of Participants With HIV Viral Suppression, Missing Imputed as Unsuppressed
HIV-1 RNA \<200 copies/ml
Time frame: 12 weeks and 24 weeks
Population: Non-inferiority analyses of HIV viral suppression by treatment arm Intent to Treat Group Missing imputed as unsuppressed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants With HIV Viral Suppression, Missing Imputed as Unsuppressed | 12 Weeks | 23 Participants |
| Extended-release Naltrexone (XR-NTX) | Number of Participants With HIV Viral Suppression, Missing Imputed as Unsuppressed | 24 Weeks | 29 Participants |
| Treatment as Usual (TAU) | Number of Participants With HIV Viral Suppression, Missing Imputed as Unsuppressed | 12 Weeks | 21 Participants |
| Treatment as Usual (TAU) | Number of Participants With HIV Viral Suppression, Missing Imputed as Unsuppressed | 24 Weeks | 29 Participants |
Primary
Number of Participants With HIV Viral Suppression, Per-protocol
HIV-1 RNA \<200 copies/ml
Time frame: 12 weeks and 24 weeks
Population: Non-inferiority analyses of HIV viral suppression by treatment arm Missing as unsuppressed Per-protocol population includes 69 participants who received at least one dose of their assigned study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants With HIV Viral Suppression, Per-protocol | 12 weeks | 11 Participants |
| Extended-release Naltrexone (XR-NTX) | Number of Participants With HIV Viral Suppression, Per-protocol | 24 weeks | 15 Participants |
| Treatment as Usual (TAU) | Number of Participants With HIV Viral Suppression, Per-protocol | 12 weeks | 16 Participants |
| Treatment as Usual (TAU) | Number of Participants With HIV Viral Suppression, Per-protocol | 24 weeks | 23 Participants |
Secondary
Average Number of Self-Reported Days of Opioid Use in Last 30 Days
Average number of days of opioid use between baseline and 24 weeks, measured by the Timeline Follow-Back (count; self-report), will be used to compare opioid use by treatment group. Confirmatory analysis will assess opioid use by the average number of days of opioid use in the last 30 days of the study (by Addiction Severity Index-lite; count; self-report) and the number of monthly urine drug screen (UDS) negative for opioids between baseline and 24 weeks (count; laboratory data).
Time frame: Between baseline and 24 weeks
Population: Per-protocol population includes participants who received at least one dose of their assigned study medication.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Average Number of Self-Reported Days of Opioid Use in Last 30 Days | Intent-to-treat | 11.73 days |
| Extended-release Naltrexone (XR-NTX) | Average Number of Self-Reported Days of Opioid Use in Last 30 Days | Per-protocol | 6.02 days |
| Treatment as Usual (TAU) | Average Number of Self-Reported Days of Opioid Use in Last 30 Days | Intent-to-treat | 14.81 days |
| Treatment as Usual (TAU) | Average Number of Self-Reported Days of Opioid Use in Last 30 Days | Per-protocol | 13.58 days |
Secondary
CD4 Count
Cluster of Differentiation 4 Absolute value of CD4 count at baseline and 24 weeks.
Time frame: Baseline and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | CD4 Count | Baseline | 380.7 cells/mm3 | Standard Deviation 248.2 |
| Extended-release Naltrexone (XR-NTX) | CD4 Count | 24 Weeks | 459.1 cells/mm3 | Standard Deviation 249.1 |
| Treatment as Usual (TAU) | CD4 Count | Baseline | 439.8 cells/mm3 | Standard Deviation 336.6 |
| Treatment as Usual (TAU) | CD4 Count | 24 Weeks | 505.1 cells/mm3 | Standard Deviation 349.1 |
Secondary
Engagement in HIV Care: 100% Antiretroviral Therapy Adherence
Number of participants taking 100% of prescribed ART doses in the past month at 24 weeks for those prescribed ART at any point during the 24 week trial (proportion; self-reported medication adherence measure). Chi-squared test comparing proportion to treatment assignment, for those prescribed ART.
Time frame: 24 weeks
Population: This outcome measure is based on participant self-report. As such, fewer participants provided data for this outcome measure than other measures where data was obtained through pharmacy or clinic attendance logs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Engagement in HIV Care: 100% Antiretroviral Therapy Adherence | 16 Participants |
| Treatment as Usual (TAU) | Engagement in HIV Care: 100% Antiretroviral Therapy Adherence | 13 Participants |
Secondary
Engagement in HIV Care: Antiretroviral Therapy Prescribed
Absolute value of participants prescribed ART at baseline and within 24 weeks following randomization. Each individual can be scored 0 (not prescribed ART) or 1 (prescribed ART) at both baseline and follow-up, after which his or her outcome score will be the follow-up score minus the baseline score. Outcomes will be analyzed via rank-based methods such as Wilcoxon rank-sum tests.
Time frame: Baseline and 24 weeks
Population: Number analyzed at 24 weeks lower than baseline due to study retention and availability of data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Engagement in HIV Care: Antiretroviral Therapy Prescribed | Baseline | 37 Participants |
| Extended-release Naltrexone (XR-NTX) | Engagement in HIV Care: Antiretroviral Therapy Prescribed | 24 Weeks | 45 Participants |
| Treatment as Usual (TAU) | Engagement in HIV Care: Antiretroviral Therapy Prescribed | Baseline | 46 Participants |
| Treatment as Usual (TAU) | Engagement in HIV Care: Antiretroviral Therapy Prescribed | 24 Weeks | 43 Participants |
Secondary
Engagement in HIV Care: Quality of Life
Past 30 day health-related quality of life as measured by the EQ-5D questionnaire at baseline and week 24. Minimum value: 0 Maximum value: 100 Higher scores mean a better outcome
Time frame: Baseline and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Engagement in HIV Care: Quality of Life | Baseline | 58 score on a scale | Standard Deviation 19.1 |
| Extended-release Naltrexone (XR-NTX) | Engagement in HIV Care: Quality of Life | 24 Weeks | 67.9 score on a scale | Standard Deviation 21.2 |
| Treatment as Usual (TAU) | Engagement in HIV Care: Quality of Life | Baseline | 64.3 score on a scale | Standard Deviation 17.6 |
| Treatment as Usual (TAU) | Engagement in HIV Care: Quality of Life | 24 Weeks | 71.2 score on a scale | Standard Deviation 19.1 |
Secondary
Number of Participants Who Had Unprotected Sex in Past 30 Days
Past 30 day unprotected sex, as measured by the Risk Assessment Battery at baseline and week 24 (binary; self-report).
Time frame: Baseline and 24 weeks
Population: Those reporting no sex are excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants Who Had Unprotected Sex in Past 30 Days | Baseline | 15 Participants |
| Extended-release Naltrexone (XR-NTX) | Number of Participants Who Had Unprotected Sex in Past 30 Days | 24 Weeks | 9 Participants |
| Treatment as Usual (TAU) | Number of Participants Who Had Unprotected Sex in Past 30 Days | Baseline | 16 Participants |
| Treatment as Usual (TAU) | Number of Participants Who Had Unprotected Sex in Past 30 Days | 24 Weeks | 9 Participants |
Secondary
Number of Participants Who Test Positive for Opioids at 24 Weeks
Number and percent of participants with UDS positive for opioids at 24 weeks.
Time frame: 24 weeks
Population: Per-protocol population includes participants who received at least one dose of their assigned study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants Who Test Positive for Opioids at 24 Weeks | Intent-to-treat | 34 Participants |
| Extended-release Naltrexone (XR-NTX) | Number of Participants Who Test Positive for Opioids at 24 Weeks | Per-protocol | 10 Participants |
| Treatment as Usual (TAU) | Number of Participants Who Test Positive for Opioids at 24 Weeks | Intent-to-treat | 40 Participants |
| Treatment as Usual (TAU) | Number of Participants Who Test Positive for Opioids at 24 Weeks | Per-protocol | 30 Participants |
Secondary
Number of Participants With at Least 1 HIV Care Visit in Past 12 Weeks
At least 1 HIV care visit in past 12 weeks
Time frame: 24 weeks
Population: This outcome measure is based on participant self-report. As such, fewer participants provided data for this outcome measure than other measures where data was obtained through pharmacy or clinic attendance logs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants With at Least 1 HIV Care Visit in Past 12 Weeks | 31 Participants |
| Treatment as Usual (TAU) | Number of Participants With at Least 1 HIV Care Visit in Past 12 Weeks | 29 Participants |
Secondary
Number of Participants With Multiple Sex Partners in Past 30 Days
Past 30 day multiple sex partners, as measured by the Risk Assessment Battery at baseline and week 24 (binary; self-report).
Time frame: Baseline and 24 weeks
Population: Two or more sex partners during past month, those reporting no sex partners are excluded
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Number of Participants With Multiple Sex Partners in Past 30 Days | Baseline | 10 Participants |
| Extended-release Naltrexone (XR-NTX) | Number of Participants With Multiple Sex Partners in Past 30 Days | 24 Weeks | 5 Participants |
| Treatment as Usual (TAU) | Number of Participants With Multiple Sex Partners in Past 30 Days | Baseline | 6 Participants |
| Treatment as Usual (TAU) | Number of Participants With Multiple Sex Partners in Past 30 Days | 24 Weeks | 6 Participants |
Secondary
Veterans Aging Cohort Study (VACS) Index
Absolute value of participant VACS Index at baseline and 24 weeks Veterans Aging Cohort Study Index Minimum value: 0 Maximum value: 164 A higher score means a worse outcome.
Time frame: Baseline and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Extended-release Naltrexone (XR-NTX) | Veterans Aging Cohort Study (VACS) Index | Baseline | 65.1 score on a scale | Standard Deviation 18.1 |
| Extended-release Naltrexone (XR-NTX) | Veterans Aging Cohort Study (VACS) Index | 24 Weeks | 54.4 score on a scale | Standard Deviation 20.7 |
| Treatment as Usual (TAU) | Veterans Aging Cohort Study (VACS) Index | Baseline | 68.4 score on a scale | Standard Deviation 24.7 |
| Treatment as Usual (TAU) | Veterans Aging Cohort Study (VACS) Index | 24 Weeks | 63.5 score on a scale | Standard Deviation 25.4 |