Clinical trial NCT03089983: Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings
Official title: Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Opioid Dependence
Addiction
HIV/AIDS
Tuberculosis
Hepatitis
Keywords: prison
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: University of Malaya
name: National Institute on Drug Abuse (NIDA)
First posted: 2017-03-24
Enrollment: 1702
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The purpose of this study is to conduct empiric studies of tuberculosis (TB) among people in prison with and without 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; b) 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 2-arm preference trial comparing post-release TB treatment completion in patients on opioid agonist treatment (methadone) vs no opioid agonist treatment in patients being treated for active or latent TB, or patients with no 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.

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, LTBI or no TB and who meet pre-incarceration DSM-V criteria for opioid dependence and who may (or may not) 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 OAT i.e. MMT, 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). Consented participants will undergo a detailed baseline assessment and administered a using Research Electronic Data Capture (REDCap) in our private research room with guidance from the research assistant (RA). Using procedures from our completed RCT of released prisoners, and in an effort to integrate patients into the health system, all participants will be met on the day of release and transitioned to Klinik Kesihatan (KKs), government clinics, (which will collaboratively act as 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 KKs using previously described protocols by the Ministry of Health with guidance from our team. 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.

Buprenorphine/Naloxone arm was removed from protocol in 2021.

Eligibility criteria: 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-), or no active TB, or no LTBI
* 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 (preferable within 25 km of community research site, but not a requirement)
* AST/ALT \<5x upper limit normal
* Malaysian citizen (non-Malaysians not eligible for receiving standard of care)

Exclusion Criteria:

* Unable to provide informed consent
* On a protease inhibitor
* Women who are pregnant or are planning on becoming pregnant

Primary outcomes:
measure: TB treatment completion rates in prison using a visual analog scale (VAS)
timeFrame: 3 to 6 months
measure: TB treatment completion rates after release from prison using a visual analog scale (VAS)
timeFrame: 3 to 6 months
Secondary outcomes:
measure: Self-reported opioid agonist treatment (MMT or no OAT) adherence using a visual analog scale (VAS)
timeFrame: 3 to 6 months
measure: Self-reported ART adherence (for HIV+ participants) using a visual analog scale (VAS)
timeFrame: 3 to 6 months
measure: Percentage of opioid negative urine tests
timeFrame: monthly for 6 months
measure: Time to opioid relapse using urine drug tests
timeFrame: monthly for 6 months
measure: Drug craving using a craving scale
timeFrame: monthly for 6 months
measure: Addiction severity, employment, legal, and social functioning using the ASI-Lite
timeFrame: every 3 months, for up to 6 months
measure: Health-related quality of life using the SF-12v2
timeFrame: every 3 months, for up to 6 months
measure: Overdose or death reported from members of social network
timeFrame: monthly for 6 months
measure: Re-incarceration reports from Ministry of Justice and self-reported arrests
timeFrame: monthly for 6 months
measure: Self-reported patient satisfaction using a questionnaire
timeFrame: every 3 months, for up to 6 months
Other outcomes:
measure: TB treatment tolerability/toxicity measured through liver function tests (AST/ALT levels)
timeFrame: monthly for up to 6 months
Locations:
city: Kajang
country: Malaysia
facility: Kajang Prison
state: Selangor
Study officials:
affiliation: Yale University
name: Frederick Altice, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Malaya
name: Adeeba Kamarulzaman, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Sheela Shenoi, MD
role: PRINCIPAL_INVESTIGATOR
References: