Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) (ADEPTT)
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|ClinicalTrials.gov Identifier: NCT03302299|
Recruitment Status : Completed
First Posted : October 5, 2017
Last Update Posted : June 10, 2021
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis HIV/AIDS Alcohol Abuse||Drug: Isoniazid 300 Mg ORAL TABLET Drug: Pyridoxine 25 Mg Oral Tablet||Phase 4|
Tuberculosis (TB) is the leading cause of mortality in persons with HIV worldwide, accounting for 20-33% of HIV-related deaths, and is a high-priority area of research in HIV/AIDS by the NIH. TB preventive therapy decreases both all-cause mortality and active TB in persons with HIV by 30-50% above and beyond the benefits of antiretroviral therapy (ART) alone. Based on these findings, the World Health Organization (WHO) recommends isoniazid (INH) preventive therapy (IPT) for all persons with HIV in resource constrained settings. However, the WHO warns against the use of IPT in persons with "regular and heavy alcohol use." This exclusion stems from concern for increased hepatotoxicity in heavy drinkers in settings where liver enzymes are not routinely monitored. Heavy drinking in persons with HIV is very common, approximately 25%, in sub-Saharan Africa (SSA). Heavy drinking increases the risk for active TB at least threefold; thus, HIV-infected alcohol users should be prioritized for TB prevention. However, no studies have systematically assessed the safety of TB preventive therapy in heavy drinkers with or without HIV infection. It is critical to examine the safety and tolerability of TB preventive therapy for HIV-infected drinkers, given the high rates of HIV, TB infection, and alcohol comorbidities worldwide. While the risk of toxicity exists, the risk of TB disease could outweigh the toxicity harms. Thus, it is also crucial to determine whether the mortality benefits outweigh the toxicity risks for this significant portion of the HIV-infected population.
In addition, TB preventive therapy is only effective if taken consistently for the full course. Alcohol use is an established risk factor for decreased ART pill taking and active TB treatment discontinuation. Whether HIV-infected drinkers on ART can be adherent to TB preventive therapy is not known. Therefore it is essential to determine the level of adherence to TB preventive therapy by HIV-infected drinkers on ART, thus this study aims to examine adherence to TB preventative therapy as well.
This is a study to examine 6 months of daily INH (6H) among N=300 persons co-infected with HIV and TB. The aims of the study are:
Aim 1: To examine the safety and tolerability of 6H in HIV/TB co-infected drinkers, measured by hepatotoxicity and treatment discontinuation rates. The main aim is to estimate safety and tolerability overall among drinkers (primary) and by level of drinking (secondary).
Aim 2: To determine the level of TB preventive therapy adherence overall among drinkers and by level of drinking, and at 3 and 6 months. The main goal of this aim is to estimate adherence overall among drinkers (primary). Secondarily the investigators will estimate adherence by level of drinking (heavy, current but not heavy drinkers, and non-drinkers) and compare adherence across drinking levels. The investigators hypothesize that adherence will be highest among the non-drinkers.
Aim 3: To determine whether the benefits of providing TB preventive therapy to HIV-infected drinkers in resource-limited settings outweigh the risks compared to no treatment. The investigators hypothesize that providing TB preventive therapy will result in longer life expectancy and quality-adjusted life expectancy than not providing TB preventive therapy (current standard of care).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||302 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||URBAN ARCH (3/5) Uganda Cohort TB Preventive Therapy for HIV-infected Alcohol Users in Uganda: an Evaluation of Safety Tolerability and Adherence|
|Actual Study Start Date :||April 7, 2017|
|Actual Primary Completion Date :||April 1, 2021|
|Actual Study Completion Date :||April 1, 2021|
Experimental: Isoniazid & pyridoxine
Isoniazid 300 mg oral tablet: 300 mg daily by mouth for 6 months. Pyridoxine 25 mg oral tablet: 25mg daily by mouth for 6 months.
Drug: Isoniazid 300 Mg ORAL TABLET
The study intervention will include a single arm given (1) 6H: 300 mg INH daily by mouth for 6 months.
Other Name: INH
Drug: Pyridoxine 25 Mg Oral Tablet
All participants will also receive 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months for the treatment duration to reduce the risk of INH-induced peripheral neuropathy.
Other Name: Vitamin B6
- Grade 3/4 hepatotoxicity [ Time Frame: Hepatotoxicity occurring during the six month course (180 pills) of INH (which may be taken over a maximum of 9 months) ]Safety will be assessed by the occurrence of a Grade 3/4 hepatotoxicity at any time during the assigned treatment period.
- Treatment discontinuation [ Time Frame: Treatment discontinuation occuring during the six month course (180 pills) of INH (which may be taken over a maximum of 9 months) ]Lack of tolerability will be defined as any treatment discontinuation prior to completion of the prescribed course (6 months of INH over a maximum period of 9 months) due to side effects or ALT/AST elevations.
- INH medication adherence by Electronic Medication Monitoring [ Time Frame: Adherence will be measured over the 6 months on INH or until INH discontinuation (whichever is shorter) ]EMM adherence will be defined as the number of pill bottle openings (no more than 1 per day counted) divided by the number of prescribed doses over the study period openings (no more than 1 per day counted) divided by the number of prescribed doses over the study period.
- Self-reported INH medication adherence by visual analog scale [ Time Frame: Self-reported INH medication adherence via VAS will be measured 3- and 6- months after starting INH ]The visual analog scale (VAS) asks the patient to identify their past month percent adherence on a visual scale that ranges from 0 to 100%. The VAS is administered at 3- and 6-month interviews. The average of the two measures for this outcome will be used for analysis.
- Self-reported INH medication adherence by the Self Rating Single Item (SRSI) scale [ Time Frame: Self-reported INH medication adherence via SRSI will be measured 3- and 6- months after starting INH ]The study will administer the Self Rating Single Item (SRSI) adherence scale, which asks participants to rate their ability to take their medications as prescribed over the past month at the 3- and 6-month interview. The lower score of the 2 surveys administered will be used.
- INH concentration in hair [ Time Frame: Measured at 3- and 6- months after INH initiation ]INH concentration in hair (ng/mg) will be measured at 3- and 6- months during INH therapy. Average concentration will be used.
- Liver injury [ Time Frame: Study screening visit ]ALT or AST elevations (>2x the upper limit of normal) at study screening
- Latent tuberculosis [ Time Frame: Study screening visit ]Latent tuberculosis assessed at screening via tuberculin skin testing
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03302299
|Mbarara University of Science and Technology/Mbarara Regional Referral Hospital|
|Principal Investigator:||Judith A Hahn, PhD, MA||University of California, San Francisco|