Extended-Release Naltrexone for Opioid Relapse Prevention Among Community Criminal Justice Participants

Transcription

1 Extended-Release Naltrexone for Opioid Relapse Prevention Among Community Criminal Justice Participants JD Lee 1, PD Friedmann 2, TW Kinlock 3, EV Nunes 4, CP O Brien 5 1. New York University School of Medicine; Bellevue Hospital Center, NY, NY 2. Providence VAMC, Rhode Island Hospital & Alpert Medical School, Brown University 3. Friends Research Institute 4. Columbia Univ. 5. Univ. Pennsylvania ClinicalTrials.gov NCT Funding: NIDA Collaborative R01s, Dana Foundation Study Drug: Alkermes, Inc.

2 Disclosures All: In-Kind Study Drug (IKSD) -Alkermes Lee JD: Investigator-Initiated Study (IIS) funding and IKSD-Alkermes; IKSD-Reckitt-Benckiser Friedmann PD: speaker-orexo O Brien C: consultant-alkermes Nunes EV: IKSD-Reckitt-Benckiser, Duramed; IIS-HealthSim, LLC; IIS-Brainsway; Advisory Board-Lilly; educat materials from Otsuka America; Advisory Board-Alkermes Kinlock T: IIS-Alkermes

3 Opioid Disorders Treatment Among Criminal Justice Clients Methadone and buprenorphine are underutilized Drug-free treatment modalities predominate Relapse and overdose are common post-release Overdose and overall mortality very high vs. age-matched Re-incarceration is extremely common

4 Medications for Opioid Disorders: Evidence in Criminal Justice Settings Efficacy Community Effectiveness Crim. Justice Feasibility Crim. Justice Effective Crim. Justice Adoption Methadone /- BUP /- XR-NTX ++ +?? + O-NTX XR-NTX s effectiveness in CJS populations is unknown

5 Specific Aims Among community-dwelling CJS-involved adults, XR-NTX vs. Treatment-as-Usual (TAU) will reduce: Aim 1. rates of opioid relapse Aim 2. other drug use, HIV risk, safety, reincarceration, coercion, cost Hypothesis: XR-NTX is effective vs. TAU at reducing rates of opioid relapse and misuse

6 Study Design 1. Adults w/ opioid dependence (DSM-IV current or lifetime) 2. parole, probation, jail/prison w/in 12 mos. 3. Not seeking agonist rx (methadone, buprenorphine) Randomization XR-NTX TAU Follow-Up every 2 weeks End of Treatment Phase: 6 months 1 o outcome: opioid relapse, rates of opioid misuse Final Follow-Up at 12, 18 months

7 Methods Design: open-label effectiveness RCT Population: volunteers only no CJS agency referrals only persons not seeking agonist rx. Sites: Providence, NYC (2x), Baltimore, Philadelphia Intervention: XR-NTX monthly IM injection + Med Mgt TAU: referrals to community treatment agonist rx. if participants desire Assessments bi-weekly (urine, TLFB); f/u months 6,12,& 18

8 Methods Primary Outcome: the event of opioid relapse 10+ days of opioid use by self-report or urine toxicology + or missing urine = 5 days of opioid use Missing = positive: complete primary outcomes Primary Analysis: Head-to-head intent-to-treat comparison of relapse Time-to-relapse: Cox Proportional Hazard w Site Co-variate % 2-weeks abstinent (non-missing, neg. urine, selfreport=0) (GEE) % urines negative vs. positve/missing (GEE) % days of self-reported opioid use (GEE) Secondary outcomes: drug/alcohol rates, HIV risk (IV, sex), SAEs/Overdose, re-incarceration, coercion, costeffectiveness Power: target sample N=360

9 Target sample N=360 Results: Study Flow 1. Pre-screened, n=2753; 2. Screened, n=437 Randomization, N=308 Ineligible, n=129 Incomplete screen: 57 Opioids+: 25 Med/psyche/LFT:19 Recent overdose: 3 BMI>35: 2 XR-NTX, n=153 TAU, n=155 FU every 2 weeks End of Treatment Phase, 6 months, N=308 1 outcome: N=308 w data available Final FU at 12, 18 months: on-going

10 Results: Follow-up Rates and XR-NTX Adherence of 14 (mean) bi-weekly visits completed Differences between arms: none Completed week 27 end-of-treatment assessment: 75% 2. 77% (711 of 918) XR-NTX monthly injections 1 st XR-NTX: 97% (1 declined; 2 failed narcan chall.) 2 nd : 88% 3 rd: 79% 4 th : 73% 5 th : 67% 6 th : 61% (1 had allergic reaction after 5 th )

11 Results: Baseline Characteristics N=308 No baseline differences 85% male, 73% parole/probation, mean age 44 Ethnicity: 48% Black, 32% Hispanic/other, 20% White 100% lifetime opioid dependence 87% lifetime heroin use 49% lifetime prescription opioid misuse 41% h/o IVDU 9% required opioid detox prior to randomizing 34% heroin/opioids use last 30 days 19% cocaine use last 30 days

12 Results at 6 months: Primary Outcome: Opioid Use XR-NTX TAU P value RR (95%CI) Primary outcome: Opioid relapse, any 66 (43%) 99 (64%) (.54,.84) Time to-relapse (median weeks) % 2-week intervals, confirmed abstinence# % Urines negative (vs. positive/missing) % Days of misuse (self-report)* < HR.48 (.35,.66) 71.04% 49.43% < OR 2.5 (1.7, 3.8) 74.11% 55.68% < OR 2.3 (1.5, 3.6) 3.94% 11.30% < (.24,.93)

13 Time to Relapse: Survival Curve

14 Results at 6 months: TAU Sought More Agonist Treatment XR-NTX TAU P value HR (RR),95%CI % Participating in outpatient program for drug/alcohol 62.33% 65.03% 0.63 RR 0.96 (0.81, 1.14) % Entering hospital for detox 2.74% 2.11% 0.73 RR 1.30 (0.30, 5.69) % Entering residential program for detox or SA services 8.90% 10.56% 0.63 RR 0.84 (0.42, 1.71) % Reported suboxone treatment month % 25.35% <0.001 RR 0.30 (0.16, 0.56) % Reported methadone treatment month % 11.27% 0.01 RR 0.30 (0.11, 0.81)

15 Results at 6 months: No Differences in Secondary Outcomes XR-NTX TAU P value Cocaine misuse days % 3.32% 3.87% 0.70 Avg # drinks/week 1.59, CI (0.73, 2.46) 1.23, CI (0.76, 1.70) 0.47 % used IV drugs 5.93% 8.62% 0.43 RAB Sex Risk Scores at 6mo (mean) Re-incarceration, any(1) (19.61%) 27 (17.42%) 0.62 HR (RR),95% CI 0.89 (0.42, 1.58) RR 0.69 (0.27, 1.75) RR 1.13 (0.70, 1.80) 1. Re-incarceration: self-report only, week 27

16 Results at 6 months: Trend toward More TAU Overdose XR-NTX TAU P value HR (RR),95%CI Overdose event na Overdose, fatal na Death, any cause na

17 Summary of Results at 6-Months All had high rates of community psychosocial outpatient participation Over ¼ of control arm reported methadone and buprenorphine treatment XR-NTX arm less opioid misuse and relapse. Time-to-relapse and the % of weeks abstinent both greater among XR-NTX No differences in secondary outcomes cocaine and alcohol use, HIV risk, re-incarceration

18 Limitations Open-label, non-placebo, unblinded Community effectiveness trial No head-to-head comparison to agonist treatment Participants generally selected bup-nx or methadone after relapsing Long-term f/u and secondary outcomes ongoing 18 mos. f/u ends May, 2015)

19 XR-NTX is Conclusions Well-tolerated and feasible over 6-months in a multisite US sample Effective at preventing opioid relapse and overdose among criminal justice-involved community volunteers Likely effective in populations not seeking or able to access agonist therapies (bup-nx, methadone)