HARAPAN II: Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings

Sponsor

Yale University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03089983

Collaborator

University of Malaya (Other), National Institute on Drug Abuse (NIDA) (NIH)

500

Enrollment

Location

Arms

87.4

Anticipated Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to conduct empiric studies of tuberculosis (TB) among prison inmates with a history of opioid dependence. This includes: a) comprehensive TB diagnostic study (symptom screening, chest x-ray, tuberculin skin test, acid-fast bacilli smear, Gene Xpert, and sputum culture) to determine best practices for screening HIV+ and HIV- prisoners;

A RCT of latent TB infection prevention strategies among HIV+ and HIV- prisoners with high prevalence of hepatitis C (HCV) using standard 40-week daily isoniazid (40H) vs short-course weekly isoniazid + rifapentine (12HR); and c) a 3-arm preference trial comparing post-release TB treatment completion in patients on opioid agonist treatment (methadone vs naltrexone implant) vs no opioid agonist treatment in patients being treated for active or latent TB who are transitioning to the community. Investigators will also use this data, and publicly available data to complete agent-based modeling for comparative and cost-effectiveness of various TB screening and treatment strategies among prisoners, and upon community transition post-release from prison.

Condition or Disease	Intervention/Treatment	Phase
Opioid Dependence Addiction HIV/AIDS Tuberculosis Hepatitis	Drug: Buprenorphine Naloxone Drug: Methadone Drug: Isoniazid Drug: Rifapentine	Phase 4

Detailed Description

Part A: All newly admitted prisoners (80-120 new inmates on admission days) undergo a complete assessment, including a brief exam and mandatory rapid HIV test by the prison medical unit. Each prisoner waiting to be evaluated will be invited for participation in TB screening activities (not currently part of standard care). If they verbally assent to wanting to learn more in a group session, their names and ID will be recorded and then invited for informed consent privately, followed by a brief survey, WHO symptom assessment, tuberculin skin testing (TST) with reading after 72 hours, sputum induction on 2 consecutive mornings for AFB smear, TB culture (results back 6-8 weeks using the BACTEC MGIT 960 liquid culture gold standard), and point-of care (POC) Gene Xpert. Each person will have phlebotomy for HBV and HCV Ab, LFTs, and if HIV+, CD4 testing (all of these are POC using Alere™). For those with CD4<50, they will undergo POC low-cost, urinary TB-LAM lateral flow testing (sensitivity=67%) (Alere™ Determine) to identify disseminated TB. Additional demographic, drug use, and TB risks will also be assessed along with prison data (release date, previous incarcerations, type of offense). Participants will then undergo CXR testing. A TB specialist will review all patients and results, ensuring that patients with suspected TB initiate treatment. All suspected or confirmed cases active TB cases in HIV+ prisoners will have ART initiated after 2 weeks of TB treatment initiation (if CNS TB not suspected) if CD4<50 and within 8 weeks for all others.

Part B: All HIV+ prisoners with latent TB infection (LTBI) (TST reaction 10 mm or greater) from part A will be asked to participate in Part B. Enrolled participants will undergo block stratified randomization, stratifying on three factors: a) CD4<350; b) HCV Ab status; and c) ART status. After randomization and allocation to 12HR or 40H, participants will be provided 12HR weekly (12 weeks) and INH daily (26 weeks) as directly observed therapy. Every 4 weeks, patients will be monitored for AST/ALT and adverse side effects. Premature treatment discontinuation will occur for any DAIDS Grade 4 toxicity or patient refusal to continue.

Part C: All HIV+ or HIV-prisoners with active or LTBI and who meet pre-incarceration DSM-V criteria for opioid dependence and who will require transitional treatment for active or latent TB infection will be approached. If these TB patients have >3 month remaining to complete their TB treatment, but are expected to discharge home before completing treatment (6 months for active TB and 26 weeks for INH), they will be eligible; among HIV+ patients, active TB incidence is 16% annually and LTBI prevalence is 84%. All HIV+ patients with active TB will receive PCP prophylaxis, as will those with LTBI and CD4<200. Because previous studies have documented negative attitudes about opioid agonist maintenance therapies (OAT) in PWIDs in Malaysia (including in prisoners) and that readiness for treatment may not be high, the investigators will enroll participants in a preference trial that will allow patients to choose their preferred OAT (MMT, BPN/NLX, or no OAT) with the help of a shared decision-making aid. Because preferences may change when better informed, they will be informed about the risks and benefits of OAT and asked to see if their preference changes. Those preferring no OAT, will be followed post-release with monthly interviews. Using previously described procedures, MMT allocated participants will initiate MMT immediately with a target dose >80mg (n.b. Cytochrome P450 induction by rifampin and ART will likely be completed before MMT is initiated, making opioid withdrawal precipitation unlikely). For participants that choose BPN/NLX, they will receive their sublingual treatment 7-10 days before release. Consented participants will undergo a detailed baseline assessment and administered a using computer-assisted survey instrument (CASI) in our private research room with guidance from the research assistant (RA). Using procedures from our recently completed RCT of released prisoners, all participants will be met on the day of release and transitioned to the integrated Cure and Care center post-release site (one of our research sites) and undergo a day-of-release interview to facilitate familiarity with our team in the community. All participants, regardless of OAT, will complete monthly follow-up visits for 6 months. MMT will be dispensed at the Cure & Care Center using previously described protocols by our team. Participants will receive BPN/NLX at a community clinic upon release. At monthly visits, patients will be assessed for adverse side effects, drug/alcohol use, and ART and TB medication adherence using the visual analogue scale (VAS). TB, HIV and substance abuse treatment outcomes will be assessed. All participants will be maintained on OAT after study completion.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings

Actual Study Start Date :

Aug 21, 2017

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: No medication-assisted treatment (control group) The control group will choose to receive no opioid agonist treatment upon release from prison.	Drug: Isoniazid Participants will be randomized to receive standard INH as TB treatment in prison for 26 weeks.
Active Comparator: Methadone maintenance treatment (MMT) Methadone maintenance treatment (MMT) is the standard of care in Malaysia, and participants who choose this arm will receive MMT upon release from prison.	Drug: Methadone Participants will receive daily or weekly doses of oral methadone. Drug: Isoniazid Participants will be randomized to receive standard INH as TB treatment in prison for 26 weeks.
Experimental: Buprenorphine/Naloxone Participants who choose buprenorphine/naloxone will receive an induction phase for 10 days and then move on to receiving it in the community for 6 months. Buprenorphine/naloxone has been authorized and is available for use in Malaysia.	Drug: Buprenorphine Naloxone Sublingual pill with a 10-day induction phase and a 6-month monitored-treatment plan, with a choice to continue after 6 months or switch to methadone. Drug: Isoniazid Participants will be randomized to receive standard INH as TB treatment in prison for 26 weeks.
Active Comparator: Standard Isoniazid (INH) for 26 weeks Participants will be randomized to receive INH, the standard of care in Malaysia, for 26 weeks while in prison.	Drug: Isoniazid Participants will be randomized to receive standard INH as TB treatment in prison for 26 weeks.
Experimental: Short-course isoniazid + rifapentine (INH + RIF) for 12 weeks Participants will be randomized to receive INH + RIF as TB treatment while in prison.	Drug: Isoniazid Participants will be randomized to receive standard INH as TB treatment in prison for 26 weeks. Drug: Rifapentine Participants will be randomized to receive short course INH + RIF as TB treatment in prison for 12 weeks.

Outcome Measures

Primary Outcome Measures

TB treatment completion rates in prison using a visual analog scale (VAS) [6 months]
TB treatment adherence in prison will be measured monthly using a visual analog scale, and will be verified using medical records. All TB treatment in prison will be administered under directly observed therapy (DOTs), and treatment administration will be recorded in the participant's prison medical record.
TB treatment completion rates after release from prison using a visual analog scale (VAS) [6 months]
Investigators will use a visual analog scale to collect monthly self-reported data (which will be verified with pill count data) on TB medication adherence to determine if implantable NTX or MMT will improve the likelihood that participants will complete their TB treatment within 6 months after release from prison.

Secondary Outcome Measures

Self-reported opioid agonist treatment (MMT or BPN/NLX) adherence using a visual analog scale (VAS) [monthly for 6 months]
Investigators will use a visual analog scale to collect monthly self-reported data (which will be verified with pharmacy data) of MMT or BPN/NLX adherence monthly.
Self-reported ART adherence (for HIV+ participants) using a visual analog scale (VAS) [monthly for 6 months]
Investigators will use a visual analog scale to collect monthly self-reported data of ART adherence in participants that are HIV-positive.
Percentage of opioid negative urine tests [monthly for 6 months]
Monthly rapid urine drug screens will be used to measure drug use.
Time to opioid relapse using urine drug tests [monthly for 6 months]
Monthly rapid urine drug screens will be used to detect opioid use.
Drug craving using a craving scale [monthly for 6 months]
A substance use craving scale will be used to measure drug craving in the past month.
Addiction severity, employment, legal, and social functioning using the ASI-Lite [every 3 months, for up to 6 months]
Addiction severity, employment, legal issues and social functioning will be measured using the short ASI-Lite questionnaire on the day of enrollment, and every 3 months for up to 6 months.
Health-related quality of life using the SF-12v2 [every 3 months, for up to 6 months]
Health-related quality of life will be measured on the day of enrollment, and every 3 months for up to 6 months.questionnaire.
Overdose or death reported from members of social network [monthly for 6 months]
Participants will be asked to identify up to five family members or friends that they are in regular contact with. If investigators cannot get a hold of the participants for monthly follow-up interviews, then members of their social network will be contacted and asked about overdose or death. Additionally, participants will be asked if they experienced an overdose in the previous month at their monthly interviews.
Re-incarceration reports from Ministry of Justice and self-reported arrests [monthly for 6 months]
If investigators cannot get a hold of the participants for monthly follow-up interviews, Ministry of Justice and Department of Prisons records will be reviewed for re-incarceration records. Additionally, participants will complete a questionnaire every 3 months to assess whether they were placed in police lock-up or arrested recently.
Self-reported patient satisfaction using a questionnaire [every 3 months, for up to 6 months]
Participants will be asked to rate their satisfaction of MMT or NTX on the day of enrollment, and every 3 months for up to 6 months.

Other Outcome Measures

TB treatment tolerability/toxicity measured through liver function tests (AST/ALT levels) [monthly for up to 6 months]
All participants will have their AST/ALT levels (rapid test using a blood sample) checked monthly for abnormal laboratory values (>5 upper limit normal) that may result in adverse events that may be related to TB treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion Criteria (part A):

Age ≥ 18 years
Newly admitted inmate at Kajang Prison

Inclusion Criteria (part B):

Age ≥ 18 years HIV-1 seropositivity
Confirmed LTBI (TST ≥ 5mm if HIV+; TST ≥ 10 mm if HIV-)
Meets DSM-V criteria for opioid dependence
9 months before release (to ensure treatment completion in prison)
AST/ALT < 3x upper limit normal

Inclusion Criteria (part C):

Age ≥ 18 years
Confirmed active (chest X-ray or laboratory) or LTBI (TST ≥ 5mm if HIV+; TST ≥ 10 mm if HIV-)
Meets DSM-V criteria for opioid dependence
< 3 months before release, but more > 3 months of TB treatment remaining.
Living with in the Klang Valley after release (within 25 km of community research site)
AST/ALT <5x upper limit normal
Malaysian citizen (non-Malaysians not eligible for receiving standard of care)