Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03089983 |
| Other study ID # |
2000020053 |
| Secondary ID |
1R01DA041271 |
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 21, 2017 |
| Est. completion date |
May 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Yale University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
